Conditions: Lung Cancer Solid Tumor Gastric Cancer Urothelial Cancer Endometrial Cancer Multiple Myeloma Myeloproliferative Neoplasms Breast Cancer Cholangiocarcinoma UC MPN
Keywords: alterations in FGF or FGFR squamous non-small cell lung cancer gastric cancer urothelial cancer endometrial cancer multiple myeloma MPN
Allocation: NON_RANDOMIZED | Intervention model: SEQUENTIAL
Enrollment: 201
Healthy volunteers: no

Brief summary:
The purpose of this study will be to evaluate the safety, tolerability, and pharmacological activity of pemigatinib in subjects with advanced malignancies. This study will have three parts, dose escalation (Part 1), dose expansion (Part 2) and combination therapy (Part 3).

Detailed description:

Arms:
arm 1: Participants self-administered oral pemigatinib 1/2/4 milligrams (mg) once daily (QD) on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 2: Participants self-administered oral pemigatinib 6 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 3: Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 4: Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 5: Participants self-administered oral pemigatinib 20 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 6: Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. arm 7: Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. arm 8: Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle. arm 9: Participants self-administered oral pemigatinib 7.5 mg twice daily (BID) on Days 1 through 21 of each 21-day cycle. arm 10: Participants self-administered oral pemigatinib 10 mg BID on Days 1 through 21 of each 21-day cycle. arm 11: Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 12: Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. arm 13: Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. arm 14: Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. arm 15: Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle. arm 16: Participants received gemcitabine (Gem) intravenously starting at 1000 mg/meters squared (m\^2) (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin (Cis) was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin. arm 17: Participants received gemcitabine intravenously starting at 1000 mg/m\^2 (30 minutes) on Days 1 and 8 of each 21-day cycle. Cisplatin was administered intravenously starting at 70 mg/m\^2 (1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle. Both gemcitabine and cisplatin doses could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of gemcitabine/cisplatin. arm 18: Trastuzumab (Tras) was administered as an open-label, commercial product at an initial dose of 8 mg/kilograms (kg) over a 90-minute intravenous infusion, followed by 6 mg/kg over a 30- to 90-minute intravenous infusion once every 3 weeks. The dose could have been adjusted for toxicity management, per commercial labeling. The investigator could have interrupted, modified, or discontinued trastuzumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of trastuzumab. arm 19: Participants received docetaxel (Doc) intravenously starting at 75 mg/m\^2 (1 hour) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued chemotherapy with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of docetaxel. arm 20: Participants received pembrolizumab (Pem) intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 9 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab. arm 21: Participants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on a 2-weeks-on therapy and 1-week-off therapy schedule. The treatment cycle consisted of: Days 1 through 14: pemigatinib QD; Days 15 through 21: treatment break. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab. arm 22: Participants received pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks on Day 1 of each cycle. The dose could have been adjusted for toxicity management per commercial labeling. The investigator could have interrupted, modified, or discontinued pembrolizumab with medical monitor approval. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. It was permissible to continue pemigatinib administration during the toxicity break of pembrolizumab. arm 23: Retifanlimab (Ref) was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 9 mg QD on Days 1 through 21 of each 21-day cycle. arm 24: Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 13.5 mg QD on Days 1 through 21 of each 21-day cycle. arm 25: Retifanlimab was administered once every 4 weeks on a 28-day cycle as an open-label product, at an initial dose of 500 mg over a 60-minute intravenous infusion. Participants self-administered oral pemigatinib 20 mg QD on Days 1 through 21 of each 21-day cycle.

Interventions: intervention 1: Pemigatinib intervention 2: Gemcitabine intervention 3: Pembrolizumab intervention 4: Docetaxel intervention 5: Trastuzumab intervention 6: Retifanlimab intervention 7: Cisplatin
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None intervention 4: None intervention 5: None intervention 6: None intervention 7: None

Protocol document:
Prot_000.pdf: 


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Protocol INCB 54828-101 Am 10 
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CONFIDENTIAL 
 
Clinical Study Protocol 
 
INCB 54828-101 
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability 
Study of INCB054828 in Subjects With Advanced Malignancies 
(FIGHT-101) 
 
Product: 
INCB054828 (pemigatinib) 
IND Number: 
 
EudraCT Number 
2016-002831-14 
Phase of Study: 
1/2 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Original Protocol (Version 0): 
17 OCT 2014 
Amendment (Version) 1: 
19 NOV 2014 
Amendment (Version) 2: 
11 JUN 2015 
Amendment (Version) 3: 
02 NOV 2015 
Amendment (Version) 4: 
09 MAR 2016 
Amendment (Version) 5: 
27 SEP 2016 
Amendment (Version) 6: 
26 JUN 2017 
Amendment (Version) 7: 
10 AUG 2018 
Amendment (Version) 8: 
11 DEC 2018 
Amendment (Version) 9: 
02 JUL 2019 
Amendment (Version) 10: 
27 MAR 2020 
 
This study will be performed in accordance with ethical principles that have their origin in the Declaration of 
Helsinki and conducted in adherence to the study Protocol, Good Clinical Practices as defined in Title 21 of the US 
Code of Federal Regulations Parts 50, 54 56, 312, and Part 11 as well as ICH GCP consolidated guidelines (E6) and 
applicable regulatory requirements. 
The information in this document is confidential.  No part of this information may be duplicated, referenced, or 
transmitted in any form or by any means (electronic, mechanical, photocopy, recording, or otherwise) without the prior 
written consent of Incyte Corporation. 


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INVESTIGATOR'S AGREEMENT 
I have received and read the Investigator's Brochure for INCB054828.  I have read the 
INCB 54828-101 Protocol Amendment 10 (Version 10 dated 27 MAR 2020) and agree to 
conduct the study as outlined.  I agree to maintain the confidentiality of all information received 
or developed in connection with this Protocol. 
 
 
 
 
 
(Printed Name of Investigator) 
 
 
 
 
 
 
 
 
(Signature of Investigator) 
 
(Date) 




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Treatment may continue as long as subjects are receiving benefit and have not met any criteria for study 
withdrawal.  Subjects who discontinue study drug will continue to be followed for subsequent anticancer 
treatments and survival. 
Part 1 Dose Escalation 
Approximately 60 subjects will be enrolled.  The study will begin with an open-label dose escalation with 
an accelerated titration design based on observing each dose level for a period of 21 days before enrolling 
the next cohort and administering the next dose level.  In Part 1, subjects who receive at least 11 out of 
14 doses of study drug at the level assigned to that cohort or have a DLT will be considered evaluable for 
determining tolerability of the dose.  Subjects enrolling but not meeting these criteria may be replaced in 
order to fill the cohort. 
The starting dose will be 1 mg.  The initial cohorts will consist of at least 1 subject each, and the doses 
may be increased up to 2-fold in successive cohorts until a Grade 2 or greater toxicity (excepting 
toxicities with a clear alternative explanation or transient abnormal laboratory values without clinically 
significant signs or symptoms) or hyperphosphatemia (HP; serum phosphate > 5.5 mg/dL) is observed, at 
which time that cohort will be expanded to at least 3 subjects.  From the point where a single-subject 
cohort is first expanded to 3 subjects, subsequent cohorts will enroll at least 3 subjects, and increases to 
study drug dose will be limited to no more than 50% in successive cohorts.  If no DLTs are observed in 
the initial 3 subjects, then the next cohort will begin enrollment.  If 1 DLT is observed in the first 
3 subjects, then 3 additional subjects will be enrolled in the cohort.  If a DLT occurs in 2 or more subjects 
in a cohort of 3 or 6, then the MTD will be deemed to have been exceeded, and the next lower dose level 
will be deemed to be the MTD.  Thus, the MTD will be defined as 1 dose level below that at which 
one-third or more of subjects in a particular cohort report a DLT.  If a DLT is observed at the initial dose 
of 1 mg QD, then a dose decrease to 0.5 mg may be considered.  An intermediate dose level may also be 
explored.  If toxicities specifically relevant to a type of malignancy are observed, a separate dose 
escalation or dose decrease group will be initiated for subjects with this malignancy. 
Continuous administration of INCB054828 
Continuous study drug administration will be tested in separate dose-escalation cohorts both in 
monotherapy cohorts and combination cohorts.  The starting dose of continuous administration will be 
lower than the MTD identified in the 2-weeks-on therapy/1-week-off therapy schedule.  Subjects who 
receive at least 18 of 21 doses of study drug at the level assigned to that cohort or who have a DLT will 
be considered evaluable for determining tolerability of the dose.  Subjects enrolling but not meeting these 
criteria may be replaced in order to fill the cohort. 
Twice daily administration of INCB054828 
Twice daily administration will be tested in a dose-escalation cohort as monotherapy only.  The BID 
starting dose will be 7.5 mg on a continuous dosing schedule (no planned dose hold).  Subjects who 
receive at least 35 of a possible 42 doses of study drug at the level assigned to that cohort or have a DLT 
will be considered evaluable for determining tolerability of the dose.  Subjects enrolling but not meeting 
these criteria may be replaced in order to fill the cohort.  A total of approximately 21 subjects will be 
enrolled in this cohort for Part 1. 
Renal Impairment 
A subgroup of approximately 20 subjects (approximately 10 subjects with moderate renal impairment and 
10 with severe) will be enrolled in Part 1 at the 13.5 mg continuous administration regimen to assess the 
effect of renal impairment on the safety and PK of INCB054828. 
Pharmacodynamic Target 
Dose escalation will proceed in the absence of an MTD to a PAD.  The PAD is defined as the point where 
approximately 67% (2 out of 3) of subjects attain HP; in a cohort of 3 subjects, if 2 out of 3 have HP, the 
cohort will be expanded to 6 (while dose escalation continues as described above).  Once the PAD is 
achieved, a new cohort will be enrolled where subjects will be treated with diet modification (decreased 


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phosphate intake) and phosphate binders, and dose escalation will continue to determine the dose at which 
at least one-third of subjects attain HP and an MTD is identified.  Alternative PAD can be defined by 
molecular endpoint such as the inhibition of FGFR and/or at least a 1.5-fold increase of serum phosphate. 
Recommended Part 2 Dose 
The RP2D (dose and/or regimen) will be the lower of the MTD or the PAD with or without concomitant 
phosphate binders; different RP2Ds may be determined for interval administration and continuous 
administration.  Multiple RP2Ds may be used going in to Part 2 and Part 3. 
Lower Dose Level Expansion 
Up to 3 additional subjects may be enrolled at any dose level for the interval and continuous 
administration monotherapy regimens, as well as the combination regimens, that is deemed to be 
pharmacodynamically active (hyperphosphatemia observed in two-thirds of treated subjects) if that dose 
level is below the MTD.  Subjects must have FGF/FGFR alteration and are required to have a baseline 
biopsy and at least 1 on-treatment biopsy (recommended at Cycle 2 Day 14 but allowed to be performed 
at any cycle; must be performed on a study drug administration day, preferably between Day 8 and 
Day 14).  Additionally, an end of treatment (EOT)/at time of progression biopsy is requested but not 
required.  
 
Part 2 Dose Expansion 
When the recommended doses and/or regimen for investigation in Part 2 (RP2D) have been determined, 
enrollment will proceed for Part 2.  It is possible that a different dose and/or regimen will be chosen for 
subjects with different types of malignancies. 
Approximately 120 subjects will be treated in expansion groups to further determine safety, tolerability, 
efficacy, PK, food effect (n ≈ 8), and PD in specific populations.  In addition, all subjects enrolling in the 
tumor-specific cohorts (n = 20 total, n = 5 per cohort) will have mandatory biopsies.  For the BID dosing 
regimen, approximately 10 subjects with FGFR3 mutated or fusion-positive advanced/metastatic bladder 
cancer will be enrolled and use the BID RP2D. 
Subjects who attain HP should follow HP management guidelines as per Protocol.  Subjects that do not 
attain HP or at least a 1.5-fold increase in serum phosphate after the first cycle of treatment should have 
their dose increased each cycle to the next previously study-assessed dose until HP or the maximum 
safely tested dose/MTD is reached. 
Part 3 Combination Dose Finding and Expansion 
Part 3 will comprise treatment groups evaluating INCB054828 when administered in combination with 
standard therapies for select solid tumors.  Part 3 will include dose finding and dose expansion.  Dose 
finding will be 3 + 3 enrollment to evaluate different doses of INCB054828 in combination with agents 
utilized in the treatment of solid tumors.  The dose expansion is to further evaluate the safety and 
preliminary efficacy of the combination in select tumor types at the selected INCB054828 dose. 
Approximately 60 subjects will be enrolled in the dose-finding group.  The starting dose for Part 3 will be 
the RP2D(s). 
Initially, at least 3 subjects will be enrolled in each treatment group for dose finding.  The treatment 
groups include INCB054828 in combination with gemcitabine/cisplatin, docetaxel, pembrolizumab, 
trastuzumab, or INCMGA00012 at the doses, schedules, and routes described below.  If in each group no 
DLTs are observed, then enrollment of the corresponding expansion will begin.  If 1 DLT is observed, 
then at least 6 subjects will be enrolled in the dose-finding treatment group.  If DLTs are observed in 2 or 
more subjects in a 3- or 6-subject group, then the dose of INCB054828 will be reduced by 25% to 50%.  
Dose assessment and dose decrease may be repeated once more.  The combination MTD will be the 
highest dose of INCB054828 in each combination at which ≤ 0/3 or 1/6 subjects experience DLTs.  The 
combination RP2D will be a dose less than or equal to the MTD/PAD dependent on emergent PD, PK, 
and safety data and may be specific to the different combination therapies.  Up to 3 additional subjects 
with known FGF/FGFR alterations may be enrolled at any Part 3 dose level if that dose level is below the 


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MTD/PAD.  In addition, the subjects enrolled in the lower dose level cohort per treatment combination 
are required to have baseline biopsy and at least 1 on-treatment biopsy (recommended at Cycle 2 Day 14 
but allowed to be performed at any cycle; must be performed on a study drug administration day, 
preferably between Day 8 and Day 14).  Additionally, an EOT/at time of progression biopsy is requested 
but not required.  
 
In the Part 3 combination expansion treatment groups, a total of approximately 75 subjects will be 
enrolled across 4 treatment groups (trastuzumab will not be expanded), including up to 6 subjects per 
combination for mandatory baseline and on-treatment biopsies. 
Study Drug, Regimen, and Mode of Administration: 
INCB054828 will be self-administered as a QD oral treatment on a 2-weeks-on therapy and 1-week-off 
therapy schedule; a continuous administration regimen will also be explored, which will include a BID 
dosing regimen.  Each dose of INCB054828 should be taken without regard to timing of meals.  On days 
when PK samples will be collected, subjects should fast for 8 hours before taking study drug in the clinic 
and fast for 1 additional hour after taking study drug.  Tablets will be available in strengths of 0.5 mg and 
2 mg; a 4.5 mg tablet will be available.  The initial starting dose for dose escalation will be 1 mg.  Dose 
escalation will proceed as described above.  One cycle will be defined as 21 days of treatment. 
Part 3:  Combination 
• Gemcitabine + cisplatin combination regimen will be administered as open-label, commercial products.  
Gemcitabine will be administered at 1000 mg/m2 intravenously (IV) on Days 1 and 8 of each 21-day 
cycle.  Cisplatin will be administered at 70 mg/m2 IV once every 3 weeks on Day 1 of each 21-day 
cycle. 
• Docetaxel will be administered as an open-label, commercial product at a starting dose of 75 mg/m2 IV 
once every 3 weeks on Day 1 of each 21-day cycle. 
• Pembrolizumab will be administered as an open-label, commercial product at a starting dose of 200 mg 
IV once every 3 weeks on Day 1 of each 21-day cycle. 
• Trastuzumab will be administered as an open-label, commercial product at an initial dose of 8 mg/kg 
over a 90-minute IV infusion, followed by 6 mg/kg over a 30- to 90-minute IV infusion once every 
3 weeks. 
• INCMGA00012 will be administered as an open-label product at an initial dose of 500 mg over a 
60-minute IV infusion once every 4 weeks.  This will be a 28-day cycle. 
Reference Therapy, Regimen, and Mode of Administration:  Not applicable. 
Duration of Participation:  Subjects may continue on study until withdrawal criteria are met.  Treatment 
duration will vary significantly between subjects, but is expected to average approximately 6 months. 
Study Population: 
Subjects with advanced malignancies who have failed a prior therapy and for whom no effective standard 
anticancer therapy is available. 
Key Inclusion Criteria: 
• 
Male or female subjects, age 18 years or older. 
• 
Part 1:  Any advanced solid tumor malignancy. 
• 
Part 1:  Subset subjects with moderate renal impairment (eGFR:  ≥ 30 to < 60 mL/min/m2) and severe 
renal impairment (eGFR:  < 30 mL/min/m2). 
Part 2:  Subjects with measurable disease with documented FGF/FGFR alteration, including multiple 
myeloma and MPNs.  For subjects enrolling in Part 2 with head and neck, vulvar, or anal cancer, 
must have evidence of positive HPV status. 


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Part 3: 
1) Dose finding:  subjects with solid tumor malignancies that have measurable disease for which 
treatment with gemcitabine + cisplatin, docetaxel, trastuzumab, and PD-1–directed therapies is 
relevant. 
2) Dose expansion:  subjects with solid tumor malignancies that have measurable disease and also 
harboring FGF/FGFR alterations for which treatment with gemcitabine + cisplatin, docetaxel, 
trastuzumab, and PD-1–directed therapies is relevant. 
• 
Has progressed after prior therapy and either there is no further effective standard anticancer therapy 
available (including subject refuses or is intolerant) or the prescribed combination therapy for subjects 
enrolling in Part 3 is considered a relevant therapy for their diagnosis. 
• 
Life expectancy > 12 weeks. 
• 
ECOG performance status: 
− 
Part 1:  0 or 1. 
− 
Parts 2 and 3:  0, 1, or 2. 
• 
Archival tumor specimen (tumor block or 25 unstained slides, minimum number of slides is 
approximately 15) or willingness to undergo a pretreatment tumor biopsy to provide a tumor block or 
25 unstained slides (minimum number of slides is approximately 15).  Archival tumor biopsies are 
acceptable at baseline and should be no more than 2 years old (preferably less than 1 year old and 
collected since the completion of the last treatment); subjects with samples older than 2 years old 
and/or with sequencing report from Foundation Medicine require approval from the sponsor medical 
monitor for exemption from the need for tumor biopsy or tumor sample requirement. 
− 
NOTE:  For subjects in Part 1, fresh tumor biopsies for the purpose of determining study 
eligibility should be limited to tumors where tissue can be safely accessed.  The medical 
monitor should be contacted before the subject is enrolled. 
Key Exclusion Criteria: 
• 
Treatment with other investigational study drug for any indication for any reason, or receipt of 
anticancer medications within 28 days before first dose of study drug (6 weeks for mitomycin-C or 
nitrosoureas, 7 days for tyrosine kinase inhibitors), but may be eligible with approval from the 
sponsor's medical monitor. 
− 
Subjects must have recovered (≤ Grade 1 or pretherapy baseline) from adverse events (AEs) 
due to previously administered therapies. 
• 
Prior receipt of a selective FGFR inhibitor within the last 6 months.  
• 
Laboratory parameters outside Protocol-defined range. 
• 
Part 1 Dose Escalation: 
− 
Hemoglobin < 10.0 g/dL (transfusions are permitted with approximately 2 weeks of washout 
required before enrollment). 
− 
Platelet count < 100 × 109/L. 
− 
Absolute neutrophil count < 1.5 × 109/L. 
− 
Total bilirubin > upper limit of normal (ULN) unless associated with subject's primary cancer 
and/or metastases and with medical monitor approval. 
− 
Aspartate aminotransferase or alanine aminotransferase > ULN unless associated with 
subject's primary cancer and/or metastases and with medical monitor approval. 
− 
Alkaline phosphatase > ULN unless associated with subject's primary cancer and/or 
metastases and with medical monitor approval. 


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− 
Creatinine clearance ≤ 60 mL/min (< 30 mL/min for urothelial carcinoma) based on the site's 
standard formula, except for a subset of subjects with moderate renal impairment 
(eGFR:  ≥ 30 to < 60 mL/min/m2) and severe renal impairment (eGFR:  < 30 mL/min/m2) 
based on the MDRD formula who will be allowed to enter the study. 
− 
Serum calcium outside of the institutional normal range, or serum albumin-corrected calcium 
outside of the institutional normal range if serum albumin is outside of the institutional 
normal range. 
− 
Serum phosphorus outside of the ULN of the institutional normal range. 
− 
Parathyroid hormone > 1.5 × ULN of the institutional normal range. 
• 
Part 2 Expansion: 
− 
Hemoglobin ≤ 9.0 g/dL (transfusions are permitted with approximately 2 weeks of washout 
required before enrollment). 
− 
Platelet count ≤ 75 × 109/L. 
− 
Absolute neutrophil count ≤ 1.0 × 109/L. 
− 
Total bilirubin ≥ 1.5 × institutional ULN unless associated with subject's primary cancer 
and/or metastases and with medical monitor approval. 
− 
Aspartate aminotransferase or alanine aminotransferase ≥ 3 × ULN unless associated with 
subject's primary cancer and/or metastases and with medical monitor approval. 
− 
Alkaline phosphatase ≥ 2.5 × ULN unless associated with subject’s primary cancer and/or 
metastases and with medical monitor approval. 
− 
Creatinine clearance ≤ 40 mL/min (< 30 mL/min for multiple myeloma or urothelial 
carcinoma) based on the site's standard formula. 
− 
Serum calcium outside of the institutional normal range, or serum albumin-corrected calcium 
outside of the institutional normal range if serum albumin is outside of the institutional 
normal range. 
− 
Serum phosphorus outside of the ULN of the institutional normal range. 
− 
Parathyroid hormone > 1.5 × ULN of the institutional normal range. 
• 
Note:  Hematological parameters do not apply to subjects with MPN. 
• 
Part 3 Combination: 
− 
Hemoglobin < 9.0 g/dL (transfusions are permitted with approximately 2 weeks of washout 
required before enrollment). 
− 
Platelet count ≤ 75 × 109/L. 
− 
Absolute neutrophil count < 1.5 × 109/L. 
− 
Total bilirubin ≥ 1.5 × institutional ULN unless associated with subject's primary cancer 
and/or metastases and with medical monitor approval. 
− 
Aspartate aminotransferase or alanine aminotransferase ≥ 3 × ULN unless associated with 
subject's primary cancer and/or metastases and with medical monitor approval. 
− 
Alkaline phosphatase ≥ 2.5 × ULN unless associated with subject's primary cancer and/or 
metastases and with medical monitor approval. 
− 
Creatinine clearance ≤ 40 mL/min based on the site's standard formula (< 30 mL/min for 
urothelial carcinoma). 
− 
International normalized ratio or prothrombin time > 1.5 × ULN, unless on warfarin. 
− 
Activated partial thromboplastin time > 1.5 × ULN. 
− 
Serum calcium outside of the institutional normal range, or serum albumin-corrected calcium 
outside of the institutional normal range when serum albumin is outside of the institutional 
normal range. 


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− 
Serum phosphorus outside of the ULN of the institutional normal range. 
− 
Parathyroid hormone > 1.5 × ULN of the institutional normal range. 
• 
History of calcium and phosphate homeostasis disorder or systemic mineral imbalance with ectopic 
calcification of soft tissues (exception:  commonly observed calcifications in soft tissues, such as the 
skin, kidney, tendons, or vessels due to injury, disease, and aging, in the absence of systemic mineral 
imbalance). 
• 
Current evidence of clinically significant corneal disorder/keratopathy (including but not limited to 
bullous/band keratopathy, corneal abrasion, inflammation/ulceration, keratoconjunctivitis), or retinal 
disorder (including but not limited to macular/retinal degeneration, diabetic retinopathy, retinal 
detachment), confirmed by ophthalmologic examination. 
• 
History or presence of an abnormal electrocardiogram (ECG) that in the investigator's opinion is 
clinically meaningful.  A screening QTc interval > 470 milliseconds, as corrected by Fridericia, is 
excluded.  For subjects with an intraventricular conduction delay (QRS interval 120 msec), the JTc 
interval may be used in place of the QTc with sponsor approval.  The JTc must be ≤ 340 milliseconds 
if JTc is used in place of the QTc. 
• 
Prior radiotherapy within 2 weeks of study treatment.  Subjects must have recovered from all 
radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.  
Evidence of fibrosis within a radiation field from prior radiotherapy is permitted with medical 
monitor approval.  A 1-week washout period is permitted for palliative radiation to non–central 
nervous system disease with medical monitor approval. 
− 
Subjects enrolled into Part 3 (pembrolizumab or INCMGA00012 combination), should have 
a minimum of a 6-month washout period after thoracic radiotherapy if > 30 Gy was received. 
• 
History of human immunodeficiency virus infection. 
• 
Untreated brain or CNS metastases or brain/CNS metastases that have progressed (eg, evidence of 
new or enlarging brain metastasis or new neurological symptoms attributable to brain/CNS 
metastases).  Subjects with treated brain metastases are eligible if there is no evidence of progression 
for at least 4 weeks after CNS-directed treatment, as ascertained by clinical examination and brain 
imaging (MRI or CT scan) during the screening period, and they are on a stable or decreasing dose of 
corticosteroids for at least 1 week. 
• 
Active chronic or current infectious disease requiring systemic antibiotic, antifungal, or antiviral 
treatment within 2 weeks prior to enrollment (subjects with asymptomatic chronic infections on 
prophylactic treatment are allowed). 
• 
History of clinically significant or uncontrolled cardiac disease including unstable angina, acute 
myocardial infarction within 6 months from Day 1 of study treatment administration, New York 
Heart Association Class III or IV congestive heart failure, or uncontrolled arrhythmia requiring 
therapy (subjects with pacemaker or with atrial fibrillation and well-controlled heart rate are allowed). 
• 
History of allergic reactions to INCB054828, any of the excipients of INCB054828 or similar 
compounds, gemcitabine, cisplatin, docetaxel, pembrolizumab, trastuzumab, or INCMGA00012.  
History of infusion allergic reactions to antibodies (eg, pembrolizumab, trastuzumab, or 
INCMGA00012) that are able to be managed with standard measures (eg, H2 blockers and/or 
steroids) are allowed. 
• 
Unable or unwilling to swallow INCB054828 or significant gastrointestinal disorder(s) that could 
interfere with the absorption, metabolism, or excretion.  
• 
Pregnant or nursing women or subjects expecting to conceive or father children within the projected 
duration of the study, starting with the screening visit through completion of safety follow-up visit 
(30-35 days after last dose).  Subjects enrolled in Part 3 combination with INCMGA00012 should 
avoid pregnancy or fathering a child starting at screening through 6 months after the last dose of 
INCMGA00012. 


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• 
Any condition that would in the investigator's judgment interfere with full participation in the study, 
including administration of study medication and attending required study visits; pose a significant 
risk to the subject; or interfere with interpretation of study data. 
• 
Subjects being considered for treatment in the trastuzumab combination group (Part 3) with left 
ventricular ejection fraction of < 50% on echocardiogram or multigated acquisition scan. 
• 
Evidence of active hepatitis B virus or hepatitis C virus infection (defined as subjects with elevated 
transaminases or cirrhosis.  Subjects with chronic HBV/HCV infection with no cirrhosis and no 
elevated transaminases are allowed). 
• 
Any prior PD-1– or PD-L1–directed treatment for which permanent discontinuation of therapy is 
recommended, per USPI. 
• 
Active autoimmune disease requiring systemic immunosuppression in excess of physiologic 
maintenance doses of corticosteroids. 
• 
Subjects receiving pembrolizumab or INCMGA00012 and have received a live vaccine within 
28 days of planned start of study treatment. 
− 
Note:  Examples of live vaccines include but are not limited to the following:  measles, 
mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus Calmette–Guérin, and 
typhoid vaccine.  Seasonal influenza vaccines for injection are generally killed virus vaccines 
and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live-attenuated 
vaccines and are not allowed. 
• 
Evidence of interstitial lung disease or active, noninfectious pneumonitis. 
Study Schedule/Procedures: 
Subjects will have regularly scheduled study visits at the clinical site as part of a 21-day cycle.  
Study visits are as follows: 
• Prescreening (allowed for subjects who require genomic sequencing for lower dose level cohorts, Part 2 
or Part 3) 
• Screening:  Days -28 through -1 
• Cycle 1:  Day 1, Day 2, Day 8, Day 14, Day 15, Day 16 
• Cycles 2 through 6:  Day 1, Day 8, Day 15 
• Cycles 7+:  Day 1 only 
• Cycle 2 (Part 2 only, food-effect study):  Day 14, Day 15 
• End of treatment 
• Safety follow-up:  30 days (+ 5 days) after end of treatment 
• Follow-up for disease status and survival:  Disease status follow-up every 57 days (± 5 days) for 
subjects who discontinue for a reason other than disease progression.  Survival follow-up every 
12 weeks (± 7 days) after discontinuation. 
Local laboratory tests: 
Study visits will include sample collection for hematology, chemistry, coagulation, endocrine monitoring, 
lipid panel, and urinalysis testing to be conducted at a local laboratory.  Additionally, the screening visit 
will include serology and fertility/pregnancy testing conducted at a local laboratory.  Subjects with 
multiple myeloma or MPNs will have bone marrow aspirate/biopsy evaluations and laboratory 
assessments as part of the disease response assessment performed by a local laboratory. 
Central laboratory tests: 
Pharmacodynamic and PK samples will be collected at some visits and shipped to the sponsor or designee 
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TABLE OF CONTENTS 
SYNOPSIS ......................................................................................................................................3 
LIST OF ABBREVIATIONS ........................................................................................................21 
1. 
INTRODUCTION ......................................................................................................24 
1.1. 
Background .................................................................................................................24 
1.1.1. 
Fibroblast Growth Factor Receptor Inhibition in Oncology .......................................24 
1.2. 
Overview of INCB054828 ..........................................................................................27 
1.2.1. 
Pharmacology of INCB054828 ..................................................................................27 
1.2.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of INCB054828 .....................27 
1.3. 
Study Rationale ...........................................................................................................28 
1.3.1. 
Rationale for Evaluating Safety and Pharmacokinetics in Subjects With 
Renal Impairment .......................................................................................................29 
1.3.2. 
Rationale for Combining INCB054828 With Chemotherapy, 
Pembrolizumab, Trastuzumab, and INCMGA00012 .................................................29 
1.3.3. 
INCMGA00012 ..........................................................................................................30 
1.4. 
Potential Risks ............................................................................................................31 
1.4.1. 
Potential Risks of INCB054828 Based on Preclinical Safety ....................................31 
1.4.2. 
Potential Risks of INCB054828 Based on Clinical Experience .................................32 
1.4.2.1. 
Study INCB 54828-101 ..............................................................................................33 
1.4.2.2. 
Pharmacokinetic/Pharmacodynamic Summary ..........................................................39 
1.4.3. 
Potential Risks of Gemcitabine and Cisplatin ............................................................40 
1.4.4. 
Potential Risks of Docetaxel .......................................................................................41 
1.4.5. 
Potential Risks of Pembrolizumab ..............................................................................41 
1.4.6. 
Potential Risks of Trastuzumab ..................................................................................41 
1.4.7. 
Potential Risks of INCMGA00012 .............................................................................42 
1.4.8. 
Potential Risks Related to the Combination Regimens ..............................................42 
1.5. 
Justification of Route, Dose Regimen, and Treatment Period ....................................43 
1.5.1. 
INCB054828 ...............................................................................................................43 
1.5.2. 
Continuous Administration of INCB054828 ..............................................................44 
1.5.2.1. 
Nonclinical ..................................................................................................................44 
1.5.2.2. 
Pharmacokinetics ........................................................................................................45 
1.5.3. 
Twice-Daily Administration of INCB054828 ............................................................45 
1.5.4. 
Gemcitabine + Cisplatin .............................................................................................45 


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1.5.5. 
Docetaxel ....................................................................................................................46 
1.5.6. 
Pembrolizumab ...........................................................................................................46 
1.5.7. 
Trastuzumab ...............................................................................................................46 
1.5.8. 
INCMGA00012 ..........................................................................................................47 
2. 
STUDY OBJECTIVES AND PURPOSE ..................................................................48 
2.1. 
Primary Objectives .....................................................................................................48 
2.2. 
Secondary Objectives .................................................................................................48 
 
48 
3. 
SUBJECT ELIGIBILITY ...........................................................................................49 
3.1. 
Subject Inclusion Criteria ...........................................................................................49 
3.2. 
Subject Exclusion Criteria ..........................................................................................50 
4. 
INVESTIGATIONAL PLAN .....................................................................................54 
4.1. 
Overall Study Design ..................................................................................................54 
4.1.1. 
Part 1 Dose Escalation ................................................................................................55 
4.1.1.1. 
Pharmacodynamic Target ...........................................................................................56 
4.1.1.2. 
Recommended Part 2 Dose .........................................................................................56 
4.1.1.3. 
Lower Dose Level Expansion .....................................................................................56 
4.1.2. 
Part 2 Dose Expansion ................................................................................................56 
4.1.3 
Part 3 Combination Dose Finding and Expansion ......................................................57 
4.2. 
Study Endpoints ..........................................................................................................59 
4.2.1. 
Primary Endpoints ......................................................................................................59 
4.2.2. 
Secondary Endpoints ..................................................................................................59 
 
59 
4.3. 
Measures Taken to Avoid Bias ...................................................................................59 
4.4. 
Number of Subjects ....................................................................................................59 
4.5. 
Study Termination ......................................................................................................59 
5. 
TREATMENT OF SUBJECTS ..................................................................................60 
5.1. 
Treatment Groups and Administration of Study Drug ...............................................60 
5.1.1. 
Treatment Regimen for INCB054828 ........................................................................60 
5.1.2. 
Treatment Regimen for Gemcitabine + Cisplatin (Part 3 Only).................................60 
5.1.3. 
Treatment Regimen for Docetaxel (Part 3 Only) .......................................................60 
5.1.4. 
Treatment Regimen for Pembrolizumab (Part 3 Only) ..............................................61 
5.1.5. 
Treatment Regimen for Trastuzumab (Part 3 Only) ...................................................61 


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5.1.6. 
Treatment Regimen for INCMGA00012 (Part 3 Only) .............................................61 
5.2. 
Treatment Compliance ................................................................................................61 
5.3. 
Randomization and Blinding ......................................................................................61 
5.4. 
Duration of Treatment and Subject Participation .......................................................61 
5.5. 
Rationale for Dose Modification ................................................................................62 
5.6. 
Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose for 
INCB054828 ...............................................................................................................62 
5.6.1. 
Management of Dose-Limiting Toxicities or Other Urgent Situations ......................63 
5.6.2. 
Follow-Up of Dose-Limiting Toxicities .....................................................................63 
5.7. 
Procedures for Cohort Review and Dose Escalation of INCB054828 .......................63 
5.8. 
Dose Modification of Study Drug ..............................................................................63 
5.8.1. 
Planned Dose Modifications for INCB054828 ...........................................................63 
5.8.2. 
Criteria and Procedures for Interruption of INCB054828 ..........................................64 
5.8.3. 
Management of Hyperphosphatemia ..........................................................................66 
5.8.4. 
Criteria for Permanent Discontinuation of INCB054828 ...........................................67 
5.8.5. 
Dose Modifications and Management of Adverse Events Associated With 
Gemcitabine + Cisplatin, Docetaxel, Pembrolizumab, or Trastuzumab ....................68 
5.8.6. 
Dose Modification and Management of Adverse Events for INCMGA00012 ..........68 
5.8.6.1. 
Management of Suspected Infusion Reactions ...........................................................68 
5.8.6.2. 
Management of Suspected Immune-Related Adverse Events ....................................69 
5.8.6.3. 
Immune-Mediated Pneumonitis ..................................................................................70 
5.8.6.4. 
Immune-Mediated Colitis ...........................................................................................70 
5.8.6.5. 
Immune-Mediated Hepatitis .......................................................................................71 
5.8.6.6. 
Immune-Mediated Endocrinopathies ..........................................................................71 
5.8.6.7. 
Immune-Mediated Nephritis and Renal Dysfunction .................................................72 
5.8.6.8. 
Immune-Mediated Hematologic Toxicities ................................................................72 
5.8.6.9. 
Immune-Mediated Skin Reactions .............................................................................73 
5.8.7. 
Permanent Discontinuation of INCMGA00012 Due to Toxicity ...............................73 
5.9. 
Withdrawal of Subjects From Study Treatment .........................................................74 
5.9.1. 
Withdrawal Criteria ....................................................................................................74 
5.9.2. 
Withdrawal Procedures ...............................................................................................74 
5.10. 
Concomitant Medications and Measures ....................................................................75 
5.11. 
Restricted Medications and Measures ........................................................................75 


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5.12. 
Prohibited Medications and Measures ........................................................................75 
6. 
STUDY ASSESSMENTS ..........................................................................................75 
6.1. 
Screening Phase ..........................................................................................................83 
6.2. 
Treatment Phase ..........................................................................................................83 
6.3. 
End of Treatment ........................................................................................................83 
6.4. 
Follow-Up Phase ........................................................................................................84 
6.4.1. 
Safety Follow-Up ........................................................................................................84 
6.4.2. 
Disease Status Follow-Up ...........................................................................................84 
6.4.3. 
Survival Follow-Up ....................................................................................................84 
6.5. 
Unscheduled Visits .....................................................................................................84 
6.6. 
Beginning and End of Study .......................................................................................84 
7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES ...........................85 
7.1. 
Administration of Informed Consent Form ................................................................85 
7.2. 
Interactive Response Technology Procedure ..............................................................85 
7.3. 
Demography and History ............................................................................................85 
7.3.1. 
Demographics and Medical History ...........................................................................85 
7.3.2. 
Prior Medications ........................................................................................................85 
7.3.3. 
Concomitant Medications ...........................................................................................85 
7.4. 
Safety Assessments .....................................................................................................86 
7.4.1. 
Adverse Events ...........................................................................................................86 
7.4.2. 
Comprehensive Physical Examination .......................................................................86 
7.4.3. 
Targeted Physical Examination ..................................................................................86 
7.4.4. 
Vital Signs ..................................................................................................................86 
7.4.5. 
Twelve-Lead Electrocardiograms ...............................................................................86 
7.4.6. 
Echocardiogram/Multigated Acquisition Scan ...........................................................87 
7.4.7. 
Comprehensive Eye Examination...............................................................................88 
7.4.8. 
Laboratory Assessments .............................................................................................88 
7.4.8.1. 
Chemistry, Hematology, Coagulation Panel, Fertility, Serology, and 
Endocrine Function Testing ........................................................................................88 
7.4.8.2. 
Urinalysis ....................................................................................................................88 
7.4.8.3. 
Pregnancy Testing ......................................................................................................88 
7.4.9. 
Evaluation of FGF and FGFR Genetic Alterations ....................................................89 
7.5. 
Efficacy Assessments .................................................................................................89 


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7.6. 
Performance and Quality of Life Assessments ...........................................................89 
7.6.1. 
Eastern Cooperative Oncology Group Performance Status ........................................89 
7.7. 
Pharmacokinetic Assessments ....................................................................................90 
7.7.1. 
Blood Sample Collection ............................................................................................90 
7.7.2. 
Food-Effect Study (Part 2 Only) .................................................................................90 
7.7.3. 
Renal Impairment Cohort ...........................................................................................92 
7.7.4. 
Urine Sample Collection (Total Urine [8-hour]) ........................................................92 
7.7.5. 
Bioanalytical Methodology and Analysis ...................................................................92 
7.8. 
Pharmacodynamic Assessments .................................................................................92 
 
93 
 
93 
 
93 
7.8.4. 
Tumor Biopsy .............................................................................................................94 
7.9. 
Other Study Procedures ..............................................................................................94 
7.9.1. 
Administration of INCB054828 .................................................................................94 
7.9.2. 
Dispensing of INCB054828 .......................................................................................95 
7.9.3. 
Assessment of Compliance With INCB054828 .........................................................95 
7.9.4. 
Distribution of Subject Reminder Cards .....................................................................95 
8. 
SAFETY MONITORING AND REPORTING .........................................................95 
8.1. 
Adverse Events ...........................................................................................................95 
8.1.1. 
Definitions and Reporting ...........................................................................................95 
8.2. 
Laboratory Test Abnormalities ...................................................................................97 
8.2.1. 
Definitions and Reporting ...........................................................................................97 
8.3. 
Serious Adverse Events ..............................................................................................97 
8.3.1. 
Definitions ..................................................................................................................97 
8.3.2. 
Reporting ....................................................................................................................98 
8.4. 
Emergency Unblinding of Treatment Assignment .....................................................99 
8.5. 
Pregnancy ...................................................................................................................99 
8.6. 
Warnings and Precautions ........................................................................................100 
8.7. 
Data Monitoring Committee .....................................................................................100 
8.8. 
Adverse Events of Special Interest ...........................................................................100 
8.9. 
Product Complaints ..................................................................................................100 
9. 
STATISTICS ............................................................................................................101 


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9.1. 
Study Populations .....................................................................................................101 
9.2. 
Selection of Sample Size ..........................................................................................101 
9.3. 
Level of Significance ................................................................................................101 
9.4. 
Statistical Analyses ...................................................................................................101 
9.4.1. 
Primary Analyses ......................................................................................................101 
9.4.2. 
Secondary Analyses ..................................................................................................101 
 
101 
9.4.4. 
Safety Analyses ........................................................................................................102 
9.4.4.1. 
Adverse Events .........................................................................................................102 
9.4.4.2. 
Clinical Laboratory Tests .........................................................................................102 
9.4.4.3. 
Vital Signs ................................................................................................................102 
9.4.4.4. 
Electrocardiograms ...................................................................................................103 
9.4.5. 
Pharmacokinetic Analysis ........................................................................................103 
9.4.5.1. 
Food Effect and Renal Impairment ...........................................................................103 
9.5. 
Data Monitoring Committee .....................................................................................104 
9.6. 
Interim Analysis ........................................................................................................104 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT .........................................104 
10.1. 
Investigational Product Description:  INCB054828 .................................................104 
10.1.1. 
Packaging, Labeling, and Preparation of INCB054828 ...........................................104 
10.1.2. 
Formulation and Chemical Properties of INCB054828 ...........................................104 
10.1.3. 
Storage and Stability of INCB054828 ......................................................................104 
10.2. 
Accountability, Handling, and Disposal of INCB054828 ........................................104 
10.3. 
Investigational Product Description:  INCMGA00012 ............................................105 
10.3.1. 
Packaging, Labeling, and Preparation of INCMGA00012 .......................................105 
10.3.2. 
Formulation and Chemical Properties of INCMGA00012 .......................................105 
10.3.3. 
Storage and Stability of INCMGA00012 .................................................................105 
10.3.4. 
Accountability, Handling, and Disposal of INCMGA00012 ...................................105 
11. 
STUDY ADMINISTRATION .................................................................................106 
11.1. 
Data Management .....................................................................................................106 
11.1.1. 
Data Collection .........................................................................................................106 
11.1.2. 
Data Management .....................................................................................................106 
11.2. 
Study Monitoring ......................................................................................................107 
11.3. 
Protocol Adherence ..................................................................................................107 


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11.4. 
Financial Disclosure .................................................................................................108 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE .......................................108 
12.1. 
Sponsor Audits..........................................................................................................108 
12.2. 
Inspection by Regulatory Authorities .......................................................................108 
13. 
ETHICS ....................................................................................................................109 
13.1. 
Ethical Conduct of the Study ....................................................................................109 
13.2. 
Written Informed Consent ........................................................................................109 
13.3. 
Ethics Review ...........................................................................................................109 
13.4. 
Data Privacy ..............................................................................................................110 
14. 
DATA HANDLING AND RECORDKEEPING .....................................................110 
14.1. 
Inspection of Records ...............................................................................................110 
14.2. 
Retention of Records ................................................................................................111 
14.3. 
Confidentiality ..........................................................................................................111 
15. 
PUBLICATION POLICY ........................................................................................111 
16. 
REFERENCES .........................................................................................................112 
APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS .............................................................................118 
APPENDIX B. PHARMACOKINETIC ANALYTICAL PARAMETERS ............................119 
APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS .....................................................................................120 
APPENDIX D. RESPONSE ASSESSMENT CRITERIA FOR MULTIPLE 
MYELOMA ..............................................................................................................121 
APPENDIX E. RESPONSE ASSESSMENT CRITERIA FOR SUBJECTS WITH 
MYELOPROLIFERATIVE NEOPLASMS ............................................................123 
APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES ..........................124 
 


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LIST OF TABLES 
Table 1: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 10% of 
Participants on Pemigatinib Monotherapy in Study INCB 54828-101 (Parts 1 
and 2 Combined) in Decreasing Order of Frequency .................................................35 
Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 10% of 
Participants on Pemigatinib Combination Therapy in Study INCB 54828-
101 (Part 3) in Decreasing Order of Frequency ..........................................................37 
Table 3: 
INCB054828 Toxicology Program .............................................................................44 
Table 4: 
Comparison of Projected pFGFR2 Inhibition for Erdafitinib and Pemigatinib 
in Various Dose Regimens .........................................................................................45 
Table 5: 
Dose Levels for INCMGA00012 in Combination With INCB054828 ......................61 
Table 6: 
Definition of Dose-Limiting Toxicity and Maximum Tolerated Dose of 
INCB054828 ...............................................................................................................62 
Table 7: 
Guidelines for Interruption and Restart of INCB054828 ...........................................65 
Table 8: 
Recommended Approach for Hyperphosphatemia Management ...............................67 
Table 9: 
Guidelines for Management of Suspected Infusion Reactions ...................................69 
Table 10: Recommended Approach to Handling Pneumonitis ...................................................70 
Table 11: Recommended Approach for Handling Enterocolitis/Diarrhea .................................70 
Table 12: Recommended Approach for Handling Hepatitis .......................................................71 
Table 13: Recommended Approach for Handling Hypophysitis ................................................71 
Table 14: Recommended Approach for Handling Thyroid Disorders ........................................72 
Table 15: Recommended Approach for Handling New Onset Diabetes Mellitus ......................72 
Table 16: Recommended Approach for Handling Nephritis and Renal Dysfunction ................72 
Table 17: Immune-Mediated Hematologic Toxicities ................................................................73 
Table 18: Recommended Approach for Handling Skin Reactions .............................................73 
Table 19: Schedule of Assessments ............................................................................................76 
Table 20: Laboratory Assessments .............................................................................................80 
Table 21: Laboratory Tests:  Required Analytes for All Indications ..........................................82 
Table 22: Laboratory Tests:  Required Analytes for Multiple Myeloma Subjects .....................82 
Table 23: Electrocardiogram Timed Measurements ...................................................................87 
Table 24: Pharmacokinetic Blood Sampling (Parts 1 and 3) ......................................................91 
Table 25: Pharmacokinetic Blood Sampling (Part 2) .................................................................91 
Table 26: Sample Collection Times for Pharmacodynamic Assessments ..................................93 


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Table 27: Criteria for Clinically Notable Vital Sign Abnormalities .........................................103 
Table 28: Criteria for Clinically Notable ECG Abnormalities .................................................103 
 
LIST OF FIGURES 
Figure 1: 
INCB054828 Plasma Concentrations (Mean ± SE) at Steady State Following 
Once-Daily Dosing of Pemigatinib as Monotherapy ..................................................39 
Figure 2: 
Serum Phosphate Versus Exposure ............................................................................40 
Figure 3: 
Study Design ...............................................................................................................58 
 


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LIST OF ABBREVIATIONS 
The following abbreviations and special terms are used in this clinical study Protocol. 
Term 
Explanation 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANC 
absolute neutrophil count 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
BCRP 
breast cancer resistance protein 
BID 
twice daily 
CFR 
Code of Federal Regulations 
CNS 
central nervous system 
CR 
complete response 
CRF 
case report form (electronic) 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
CYP 
cytochrome P450 
DDI 
drug-drug interaction 
DLT 
dose-limiting toxicity 
DNA 
deoxyribonucleic acid 
 
 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
eGFR 
epidermal growth factor receptor 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FGF 
fibroblast growth factor 
FGFR 
fibroblast growth factor receptor 
FISH 
fluorescent in situ hybridization 
GCP 
Good Clinical Practice 
GLP 
Good Laboratory Practices 
HBV 
hepatitis B virus 
HCV 
hepatitis C virus 
HED 
human equivalent dose 
HIPAA 
Health Insurance Portability and Accountability Act of 1996 
HNC 
head and neck cancer 
HP 
hyperphosphatemia 


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Term 
Explanation 
IB 
Investigator's Brochure 
ICF 
informed consent form  
ICH 
International Council on Harmonisation of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IDE 
Investigational Device Exemption 
IEC 
Independent Ethics Committee 
IMWG 
International Myeloma Working Group 
IN 
Investigator Notification 
INR 
international normalized ratio 
irAE 
immune-related adverse event 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IV 
intravenously 
LVEF 
left ventricular ejection fraction 
MDRD 
Modification of Diet in Renal Disease 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPN 
myeloproliferative neoplasm 
MRI 
magnetic resonance imaging 
MTD 
maximum tolerated dose 
MUGA 
multigated acquisition (scan) 
NSAID 
nonsteroidal anti-inflammatory drug 
NOAEL 
no-observed-adverse-effect level 
NSCLC 
non–small cell lung cancer 
OCT 
organic cation transporter 
ORR 
overall response rate 
PAD 
pharmacologically active dose 
PBPK 
physiologically based pharmacokinetic 
PCR 
polymerase chain reaction 
PD 
pharmacodynamics 
PD-1 
programmed cell death-1 
PET 
positron emission tomography 
 
 
P-gp 
P-glycoprotein 
PK 
pharmacokinetics 
PR 
partial response 
PT 
prothrombin time 
Q2W 
every 2 weeks 
Q4W 
every 4 weeks 
QD 
once daily 


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Term 
Explanation 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RNA 
ribonucleic acid 
RP2D 
recommended Part 2 dose 
RPED 
retinal pigmented epithelium detachment 
SAE 
serious adverse event 
SD 
stable disease 
SmPC 
Summary of Product Characteristics 
SRD 
serous retinal detachment 
SUSAR 
suspected unexpected serious adverse reaction 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 
USPI 
United States Package Insert 


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1. 
INTRODUCTION 
1.1. 
Background 
INCB054828 is an inhibitor of the fibroblast growth factor receptor (FGFR) family of receptor 
tyrosine kinases that is proposed for the treatment of malignant diseases.  Aberrant signaling 
through FGFR resulting from gene amplification or mutation, chromosomal translocation, and 
ligand-dependent activation of the receptors has been demonstrated in multiple types of human 
cancers.  Fibroblast growth factor receptor signaling contributes to the development of 
malignancies by promoting tumor cell proliferation, survival, migration, and angiogenesis.  
Incyte is proposing to study INCB054828 for the treatment of advanced malignancies.  Refer to 
the Investigator's Brochure (IB) for additional background information on INCB054828. 
1.1.1. 
Fibroblast Growth Factor Receptor Inhibition in Oncology 
The mammalian FGFR family is composed of 4 highly conserved receptors (FGFR1, FGFR2, 
FGFR3, and FGFR4) that have an extracellular ligand binding domain, a single transmembrane 
domain, and an intracellular tyrosine kinase domain.  Eighteen fibroblast growth factor (FGF) 
ligands, divided into canonical and hormonal FGFs, bind to FGFRs leading to receptor 
dimerization, activation of the kinase domain, and transphosphorylation of the receptors 
(Eswarakumar et al 2005).  Subsequent signal transduction occurs through phosphorylation of 
substrate proteins such as FGFR substrate 2 that leads to activation of the RAS–
mitogen-activated protein kinase and PI3 kinase–protein kinase B pathways and phospholipase 
Cγ that activates the protein kinase C pathway.  In some cellular contexts, signal transducer and 
activator of transcription proteins are also activated by FGFRs.  Signaling through the 
FGF-FGFR pathway is tightly controlled through feedback regulation.  Mitogen-activated 
protein kinase phosphatases and Sprouty proteins are upregulated upon FGFR stimulation and 
antagonize FGF-dependent activation of extracellular signal-regulated kinases.  In many cases, 
FGFR pathway activation promotes cell proliferation, survival, and migration; however, cellular 
context plays an important role, and in certain tissues, FGFR signaling results in growth arrest 
and cellular differentiation (Dailey et al 2005). 
Fibroblast growth factor ligands and FGFRs are widely expressed during development, and 
FGF-FGFR signaling is essential during embryonic development.  Knockout mouse models of 
many FGF and FGFR genes exhibit lethal phenotypes from impaired organogenesis 
(Eswarakumar et al 2005).  Activating mutations in FGFR3 are associated with congenital 
skeletal dysplasias such as achondroplasia and thanatophoric dysplasia, and activating mutations 
in FGFR2 are associated with a number of autosomal dominant craniosynostotic disorders 
including Crouzon and Apert syndromes.  In adults, FGF-FGFR signaling is involved in 
angiogenesis during wound healing.  The hormonal FGF ligands contribute to regulation of 
metabolic pathways involving lipid, glucose, phosphate, and Vitamin D (Itoh 2010).  Genetic 
defects in the FGF23 signaling pathway lead to disordered phosphate metabolism:  loss of 
function mutations in FGF23 or its signaling result in retention of phosphate and tissue 
mineralization, while gain of function mutations in the FGF23 pathway manifests as 
hypophosphatemic Rickets syndrome (Farrow and White 2010). 


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There is strong genetic and functional evidence that dysregulation of FGFR can lead to the 
establishment and progression of cancer.  Genetic alterations in FGFR1, FGFR2, and FGFR3 
have been described in many tumor types (Knights and Cook 2010, Turner and Grose 2010).  
These include activating mutations, translocations, and gene amplification resulting in 
ligand-independent, constitutive activation of the receptors or aberrant ligand-dependent 
signaling through FGFRs.  Fibroblast growth factor receptor 1 is activated primarily through 
amplification of the 8p11 locus found in approximately 15% of squamous lung cancer and 10% 
of estrogen receptor–positive breast cancer (Weiss et al 2010, Elbauomy Elsheikh et al 2007).  
The FGFR1 kinase domain is also found to be translocated to a variety of gene loci in 8p11 
myeloproliferative neoplasms (MPNs) that leads to constitutive kinase activity of the FGFR1 
fusion protein (Goradia et al 2008).  Fibroblast growth factor receptor 2 is found to be activated 
by gene amplification in a number of tumor types including gastric cancer and breast cancer and 
by mutation in endometrial cancer (Kunii et al 2008, Dutt et al 2008).  Mutations that lead to 
activation of FGFR3 occur in 50% to 70% of superficial bladder cancer.  The most prevalent 
FGFR3 mutations are Ser to Cys changes in the extracellular domain that promote 
autodimerization and ligand-independent activation of signaling (di Martino et al 2009, 
Cancer Genome Atlas Research Network 2014).  These mutations match germline mutations in 
FGFR3 that are described in congenital skeletal dysplasias (Greulich and Pollock 2011).  
Translocations involving FGFR3 have been also been described in bladder cancer including the 
intrachromosomal rearrangement generating the FGFR3-TACC3 fusion (Williams et al 2013).  
Fibroblast growth factor receptor 3 is a target of the t(4;14) translocation that affects 
approximately 15% of multiple myeloma subjects (Chesi et al 1997).  This balanced 
translocation adjoins the FGFR3 coding sequence to the strong IgH enhancer elements in plasma 
cells and drives high levels of FGFR3 expression.  Finally, recent large-scale tumor sequencing 
efforts have uncovered multiple, but rare, transforming alterations in FGFR genes across a 
number of tumor histologies (Liao et al 2013, Wu et al 2013).  In addition to these examples 
where FGFR dysregulation is a primary driver of tumorigenesis, FGFR has been reported to be a 
mechanism for resistance to hormone therapy in breast cancer and to epidermal growth factor 
receptor (eGFR) inhibitors in non–small cell lung cancer (NSCLC) by providing an alternative 
survival pathway (Turner et al 2010, Ware et al 2010). 
Dysregulation of FGF ligands has also been reported in many human cancers.  Preclinical studies 
have shown that high levels of FGF ligands such as FGF2 promote cancer cell resistance to 
radiation, chemotherapeutics, and targeted cancer drugs (Fuks et al 1994, Pardo et al 2002, 
Terai et al 2013).  In triple negative breast cancer, upregulation of both FGF ligands and FGFR 
creates an autocrine loop that supports tumor cell growth and survival (Sharpe et al 2011).  
Clinically, detection of high levels of FGF2 in tumors is associated with poorer outcome in 
several tumor types including NSCLC (Donnem et al 2009, Rades et al 2012). 
A substantial body of evidence supports that genetically activated FGFR pathway sensitizes 
FGFR-altered cancer cells to knockdown or inhibition of these receptors (Kunii et al 2008, 
Qing et al 2009, Weiss et al 2010, Lamont et al 2011).  A large screen of more than 500 tumor 
cell lines with a selective FGFR inhibitor demonstrated that only a small percentage (5.9%) of all 
cells are sensitive to FGFR inhibition, and growth suppressed cell lines were highly enriched for 
FGFR alterations (Guagnano et al 2012).  These results demonstrate that FGFR inhibitors are 
active in a targeted manner against cancers with activated FGFR pathway.  An implication of 
these data is that selection based on molecular-, genetic-, or protein-based diagnostic tests for 


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specific FGFR alterations in tumors may be important for identifying subjects most likely to 
benefit from an FGFR inhibitor. 
Results from early clinical studies of selective FGFR inhibitors have shown a tolerable safety 
profile for the class and have shown preliminary signs of clinical benefit in subjects selected for 
lesions of FGFRs.  The safety and clinical activity of AZD4547 was evaluated in a Phase 1 study 
where subjects were prospectively selected for FGFR1 or FRFR2 gene amplification by 
fluorescent in situ hybridization (FISH).  Of 21 subjects dosed with AZD4547, 7 subjects had 
FGFR amplifications and 3 subjects (one each squamous NSCLC, breast cancer, and bladder 
cancer) had target lesion shrinkage or prolonged disease stabilization (Kilgour et al 2014).  In a 
Phase 1 expansion of subjects with previously treated Stage IV FGFR1-amplified squamous 
NSCLC, 14 subjects were evaluable for tumor response and there was 1 partial response (PR) 
and 4 stable disease (SD) observed (Paik et al 2014).  In a separate expansion cohort of 
13 subjects with advanced/metastatic gastric and gastroesophageal cancer, preliminary efficacy 
of AZD4547 was demonstrated with 1 PR and 4 SD; all 4 subjects had an FGFR amplification 
(Arkenau et al 2014).  In the first in human study of JNJ-42756493, 37 subjects were treated on a 
once-daily (QD) continuous treatment schedule at 6 different rising dose levels.  One 
dose-limiting toxicity (DLT) of Grade 3 aspartate aminotransferase (AST)/alanine 
aminotransferase (ALT) elevation was observed at the highest dose level and 9 mg QD was 
identified as the recommended Part 2 dose (RP2D).  As of the data cutoff, 8 subjects were 
enrolled with an FGFR aberration and there was 1 PR in bladder cancer with an FGFR3-TACC3 
translocation and 1 near complete response (CR) in a subject with urothelial cancer of the renal 
pelvis with an FGFR2 truncation.  Four subjects with FGFR1 amplification (2 lung cancer, 
1 chondrosarcoma, and 1 breast cancer) had SD (Bahleda et al 2014).  An ongoing Phase 1 study 
of the selective pan-FGFR inhibitor BGJ398 has also shown a tolerable safety profile and 
preliminary efficacy in multiple tumor types.  The study enrolled subjects with any type of FGFR 
genetic alteration.  A 125 mg QD dose of BGJ398 was identified as the maximum tolerated 
dose (MTD).  Preliminary data shows activity in urothelial carcinoma with FGFR3-activating 
mutations, FGFR1-amplified SCC lung cancer, cholangiocarcinoma with an FGFR2 gene fusion, 
and FGFR1-amplified breast cancer (Sequist et al 2014). 
An on-target pharmacologic effect of FGFR inhibition in clinical studies is hyperphosphatemia 
(HP).  In the Phase 1 study of BGJ398, at the MTD (125 mg QD dose), HP was reported in 78% 
of subjects (n = 41 subjects).  Hyperphosphatemia was managed with diet modifications, 
phosphate-lowering therapy, or dose reductions.  In future clinical studies of BGJ398, a 3-week 
on-therapy and 1-week off-therapy treatment schedule will be used based on the improved safety 
profile (Sequist et al 2014).  JNJ-42756493 has shown a similar profile for HP.  In the Phase 1 
study where 6 dose levels were evaluated, 60% of subjects (n = 37 subjects) had HP reported and 
it was managed successfully with concomitant phosphate-lowering therapy and dose 
interruptions.  A 9-mg QD continuous treatment schedule was chosen as the RP2D 
(Dienstmann et al 2014, Bahleda et al 2014). 
Based on these preliminary data, targeting FGFR may be efficacious in several human cancers 
where alterations in the FGF-FGFR pathway have been established.  INCB054828 is a potent 
selective inhibitor of FGFR1, FGFR2, and FGFR3 and is proposed for the treatment of advanced 
malignancies with FGFR alterations. 


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1.2. 
Overview of INCB054828 
1.2.1. 
Pharmacology of INCB054828 
INCB054828 is an inhibitor of the FGFR family of receptor tyrosine kinases that is proposed for 
the treatment of malignant diseases.  In vitro, INCB054828 inhibits the kinase activity of 
FGFR1, FGFR2, and FGFR3 with IC50 values ranging from 0.39 to 1.2 nM.  In enzyme assays 
versus a panel of non-FGFR kinases, INCB054828 is highly selective.  In cellular assays, 
INCB054828 inhibits autophosphorylation of FGFR proteins with IC50 values of 3.1 to 3.7 nM 
and potently inhibits signal transduction by FGFR to downstream markers of pathway activation.  
Cancer cell lines that have genetic alterations in FGFR1, FGFR2, and FGFR3 are sensitive to 
INCB054828 with growth inhibitory IC50 values in the range of 3 to 50 nM; however, cancer cell 
lines or normal cells without FGFR dependence are much less sensitive (IC50 > 1500 nM).  In a 
human whole blood assay, INCB054828 blocked phosphorylation of FGFR2 with an IC50 value 
of 10.9 nM.  These data indicate that INCB054828 is potent and selective inhibitor of FGFR1, 
FGFR2, and FGFR3. 
In vivo, INCB054828 was evaluated in 3 FGFR-dependent tumor models including H1581 
FGFR1-dependent lung, KATOIII FGFR2-dependent gastric, and RT112 FGFR3-dependent 
bladder cancer.  Pharmacokinetic-pharmacodynamic (PK-PD) analysis of pFGFR2 inhibition in 
tumors revealed an in vivo IC50 value of 22.6 nM.  Maximum tumor inhibition was observed 
with once-daily doses of 0.3 to 1 mg/kg in all 3 models and corresponded to plasma drug levels 
that exceeded the whole blood IC50 for greater than 12 hours.  At the clinical target dose of 6 mg 
QD, the whole blood IC50 is anticipated to be covered for the treatment interval and therefore is 
supported by the preclinical data.  Serum phosphate, an endogenous PD marker for FGFR 
inhibition, increased in a dose-dependent manner in mice following a single dose of 
INCB054828. 
In summary, pharmacological data obtained in both in vitro and in vivo model systems support 
the potential utility of orally administered INCB054828 in the treatment of cancer. 
1.2.2. 
Nonclinical Drug Metabolism and Pharmacokinetics of INCB054828 
The absorption, distribution, metabolism, and excretion of INCB054828 have been studied in 
Sprague Dawley rats, cynomolgus monkeys, and beagle dogs.  The systemic clearance of 
INCB054828 was low in monkeys and dogs (8% and 10% of hepatic blood flow, respectively), 
but moderate in rats (31% of hepatic blood flow).  INCB054828 exhibits a low to moderate 
volume of distribution in all 3 species, ranging from 0.584 (monkey) to 3.49 (dog) L/kg.  The 
terminal elimination half-life following intravenous (IV) administration ranged from 4.0 hours 
(rat) to 15.7 hours (dog).  The renal excretion of intact INCB054828 was 9% in rats, while these 
values were 36% and 22% in monkeys and dogs, respectively.  Metabolism and renal clearance 
are the major elimination routes for INCB054828.  The unbound renal clearance of INCB054828 
exceeds the glomerular filtration rate in dogs and monkeys, suggesting active secretion mediated 
by transporters.  The distribution of INCB054828 across the rat blood-brain barrier is limited, 
presumably due to interactions with efflux transporters.  INCB054828 was absorbed rapidly with 
tmax values ranging from 0.56 hours to 2.0 hours.  The oral bioavailability of INCB054828 was 
29% in monkeys, 98% in dogs, and complete in rats. 


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Interactions of INCB054828 with some of the commonly encountered uptake and efflux 
transporters were determined in vitro.  The permeability of INCB054828 is high in Caco-2 cells 
(11 × 10-6 cm/sec) at a nominal concentration of 50 μM.  In vitro transport studies indicate that 
INCB054828 is a substrate of both P-glycoprotein (P-gp) and breast cancer resistance protein 
(BCRP); however, the efflux mediated by P-gp and BCRP was saturated at concentrations of 
1 μM and 30 μM, respectively, in vitro.  Therefore, it is unlikely that efflux by these 
2 transporters plays an important role in the oral absorption of INCB054828.  INCB054828 is 
also an inhibitor of P-gp, with an IC50 value of 4.8 μM, and a potent inhibitor of organic cation 
transporter (OCT) 2, with an IC50 value of 0.075 μM.  The ratio of total unbound Cmax/IC50 for 
OCT2 is above 0.1.  A physiologically based pharmacokinetic (PBPK) model was developed to 
evaluate DDIs with P-gp and OCT2 substrates.  Based on the in vitro data and PBPK modeling, 
in vivo drug interaction studies for INCB054828 as a P-gp inhibitor and as an OCT2 inhibitor are 
not needed.  INCB054828 is not an inhibitor of OATP1 B1 or OAT 1. 
The plasma protein binding of INCB054828 is high in all species tested with ex vivo free 
fraction of 4.0% and 8.6% in rats and monkeys, respectively.  The free fraction in humans is 
9.4%, the average value from in vitro serum and plasma protein binding determinations. 
INCB054828 is predominantly metabolized by cytochrome P450 (CYP) 3A4.  INCB054828 is 
not a potent reversible inhibitor of the major CYPs evaluated or there was no evidence of 
metabolism-dependent inhibition noted (IC50 values > 25 μM).  Therefore, the potential for 
INCB054828 to cause clinical DDIs via inhibition of CYP is low at the projected clinical dose.  
The major in vivo metabolites identified were M2, an O-demethylated metabolite, in rat plasma, 
and M5, a bis-hydroxylated metabolite, in cynomolgus monkey plasma.  The most abundant 
in vitro metabolite was M6, an oxidative metabolite.  There were no human-specific metabolites 
noted using in vitro systems.  There is no evidence of chemical reactivity subsequent to 
metabolism. 
1.3. 
Study Rationale 
Cancer has several common characteristics that can be observed across numerous tumor types.  
One common characteristic is the uncontrolled growth and survival of cells and their ability to 
become invasive throughout the body.  Fibroblast growth factor signaling produces mitogenic, 
anti-apoptotic, and angiogenic responses in cells, which leads to a deregulated state.  Evidence 
from several in vitro and in vivo tumor models has established the FGFs and FGFRs as 
oncogenes and their expression has been found in numerous solid tumors or hematological 
malignancies.  Several genetic alterations have been shown to generate overexpression of the 
FGF receptor, produce a receptor that is constitutively active, or lead it to a state where there is 
reduced dependence on ligand binding for activation (Knights and Cook 2010). 
Tyrosine kinases are an especially important target in cancer therapy as they have a key role in 
growth factor signaling.  Several tyrosine kinase inhibitors have been shown to be effective 
antitumor agents and have been approved in multiple oncology indications (Arora and 
Scholar 2005).  In NSCLC, eGFR inhibitors have been shown to significantly improve survival 
(Shien et al 2014).  Preliminary data from ongoing Phase 1 studies with the selective FGFR 
inhibitors AZD4547, JNJ-42756493, and BGJ398 have shown a tolerable safety profile for the 
class and signs of efficacy in tumors that have FGFR genetic alterations.  INCB054828 is a 
potent inhibitor of the kinase activity of FGFR1, FGFR2, and FGFR3 and has been shown to 




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1.3.3. 
INCMGA00012 
INCMGA00012 is a humanized, hinge-stabilized, IgG4κ mAb that recognizes human PD-1.  
INCMGA00012 contains a human IgG4 Fc domain to limit effector function while retaining 
neonatal FcR binding to extend circulating half-life.  INCMGA00012 is designed to target PD-1 
expressing cells, including T cells, and sustain/restore their effector function by blocking 
checkpoint inhibitory interactions between PD-1 and its 2 ligands, PD-L1 and PD-L2. 
In vitro studies with INCMGA00012 have demonstrated high affinity binding to both 
recombinant human and cynomolgus monkey PD-1 as well as to PD-1 naturally expressed on the 
cell surface, including on T cells.  Consistent with its intended mechanism of action and 
functional properties, INCMGA00012 has been shown to inhibit the binding of PD-L1 and 
PD-L2 to PD-1, to disrupt the PD-1/PD-L1 inhibitory axis, and to enhance IFN-γ secretion in 
human PBMCs stimulated with the superantigen, staphylococcal enterotoxin B, with activity 
comparable to replicas of pembrolizumab and nivolumab (generated by MacroGenics, Inc. based 
on the published sequences of these antibodies).  INCMGA00012 does not induce ADCC or 
CDC, mitogenic activity, hemolysis, or cytokine release. 
Administration of INCMGA00012 via IV infusion once weekly at levels of 10, 40, or 150 mg/kg 
was well tolerated in cynomolgus monkeys.  The only findings related to INCMGA00012 were 
modest decreases in lymphocytes after the first infusion and microscopic changes at the IV 
administration site, consisting of minimal multifocal perivascular mononuclear cell infiltrates 
within the superficial dermis (an expected reaction to repeated injection of an exogenous 
protein).  Other microscopic changes consisted of diffuse patterns of immune cell infiltration, 
consistent with the mechanism of action of anti–PD-1 antibodies, and similar to what has been 
reported in repeat-dose studies in monkeys with nivolumab or pembrolizumab 
(FDA Pharmacology Reviews for Keytruda and Opdivo). 
Phase 1 results of INCMGA00012 in subjects with advanced cancer (N = 37) have been 
presented (Lakhani et al 2017).  Doses ranging from 1 to 10 mg/kg of INCMGA00012 
demonstrated acceptable tolerability with no DLT observed at any dose level.  An MTD was not 
reached.  Treatment-related AEs ≥ Grade 3 occurred in 4/37 (10.8%) subjects, and included 
increased lipase (n = 3) and vulvovaginal ulceration/inflammation (n = 1).  The most common 
treatment-related AEs were fatigue (n = 9, 24.3%), rash (n = 5, 13.5%), nausea (n = 5, 13.5%), 
tumor flare (n = 4, 10.8%), and pruritus (n = 4, 10.8%).  A single treatment-related SAE of 
aphasia (occurring in the setting of new brain metastases) was reported.  Immune-related AEs 
were limited to rash (n = 5, 13.5%), hypothyroidism (n = 3, 8.1%), hyperthyroidism 
(n = 2, 5.4%), vaginal ulceration/inflammation (n = 1, 2.7%), and infusion-related reaction 
(n = 1, 2.7%).  For both the 3 and 10 mg/kg dose levels Cmax and AUC∞ were dose proportional.  
T½ (β) was approximately 17 days, and steady state was achieved in approximately 85 days.  Full 
and sustained receptor occupancy of INCMGA00012 on both CD4+ and CD8+ T cells along 
with complete loss of competing fluorescently labeled anti–PD-1 staining (eJBio105 clone) were 
seen at all dose levels. 
INCMGA00012 is currently being evaluated in expansion cohorts of 35 subjects each 
(INCMGA 0012-102).  These include:  cervical cancer, non−small cell lung cancer, selected 
sarcoma subtypes, and endometrial cancer (including MSI-H, dMMR, and/or POLE exonuclease 
domain mutation positive disease). 


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Interim results for the expansion cohorts have recently been presented (Mehnert et al 2018).  A 
total of 132 subjects were enrolled into the disease-specific expansion cohorts and another 30 in 
the tumor agnostic flat dosing cohorts at 500 and 750 mg Q4W.  Subjects were predominantly 
Caucasian and female; the median age ranged from 44 for the sarcoma cohort to 64 for 
endometrial cancer.  The most frequently reported TEAEs (> 10%) in subjects receiving 
body-weight based dosing were fatigue, diarrhea, and dyspnea.  The most frequently reported 
TEAEs (≥ 20%) in subjects receiving the fixed dose of 500 mg Q4W were fatigue, blood 
alkaline phosphatase increased, and blood bilirubin increased.  Overall, 23/199 (12%) of subjects 
exposed to INCMGA00012 in the study have experienced irAEs.  Most irAEs were transient, 
with the exception of endocrine-related irAEs.  Non-endocrine irAEs that did not resolve were 
lipase increased, stomatitis, proctitis, diarrhea, ALT increased, and blood bilirubin increased (all 
1 subject each).  There were no fatal irAEs.  Confirmed RECIST responses were seen in all of 
the expansion cohorts. 
INCMGA00012 will be evaluated in combination with INCB054828 in the proposed study.  
1.4. 
Potential Risks 
1.4.1. 
Potential Risks of INCB054828 Based on Preclinical Safety 
The most prominent findings following repeat-dose exposure to INCB054828 in both rats and 
monkeys were HP, physeal dysplasia, and soft tissue mineralization.  Mineralization was 
observed in numerous tissues including the kidney, stomach, arteries (gastric and pulmonary), 
ovaries (monkey only), and eyes (cornea; rat only).  Soft tissue mineralization was not reversible, 
while physeal and cartilage findings were reversible.  
Hyperphosphatemia, physeal dysplasia, and soft tissue mineralization have been reported in 
rodents and large animals following administration of selective FGFR inhibitors 
(Brown et al 2005, Brown 2010, Wöhrle et al 2011, Yanochko et al 2013).  These observations 
can be explained by the pharmacological action of FGFR inhibition.  Fibroblast growth factor 23 
(FGF-23)–mediated signaling negatively affects renal vitamin D biosynthesis by transcriptional 
repression of CYP27B1, which catalyzes the production of the biologically active vitamin D 
metabolite 1,25(OH)2D3, and by induction of CYP24A1, which converts 1,25(OH)2D3 into a 
metabolite that is less biologically active.  Additionally, it has been published that FGF-23 
suppresses renal phosphate reabsorption by decreasing the expression of the sodium-phosphate 
cotransporters NPT2A and NPT2C in the brush-border membrane of proximal tubule epithelial 
cells (Baum et al 2005, Shimada et al 2001, Shimada et al 2004a, Shimada et al 2004b).  
Wöhrle et al (2011) demonstrated that FGFR inhibition by oral administration of PD176067 
counteracts the biologic activity of FGF-23 in the kidney, leading to HP and hypervitaminosis D. 
In rats, the mineralization was similar in distribution and morphology to that occasionally 
observed in normal animals; thus it is likely that the increased incidence of mineralization in 
various tissues at these doses represents a test article–related exacerbation of a spontaneously 
occurring condition.  While soft tissue mineralization was not reversible during 28-day recovery 
period, there was also no evidence of progression or worsening of this effect.  Soft tissue 
mineralization in monkeys was observed only at 3 mg/kg per day in the 10-day range-finding 
study and was not assessed for reversibility.  No evidence of mineralization was found at the 
doses tested in the 28-day study in monkeys. 


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Moderate lens opacities (capsule, posterior) in one 0.33 mg/kg per day and one 1 mg/kg per day 
males and slight attenuation of retinal vessels in one 1 mg/kg per day female were observed in 
monkeys at the end of treatment (EOT) period on the 28-day Good Laboratory Practice (GLP) 
study.  These findings were not present during the pretest period and thus a relationship to 
INCB054828 cannot be dismissed.  However, lens opacities are occasionally observed in normal 
cynomolgus monkeys of similar age and origin according to the testing facility historical control 
data.  Persistence of lens opacity in 1 animal at the end of recovery period suggests that this 
finding is not reversible. 
Fully reversible mild-to-moderate elevation of ALT and AST were noted at the EOT period in 
the 28-day monkey study at doses ≥ 0.33 mg/kg per day; these changes were not associated with 
changes in other hepatobiliary parameters or microscopic changes in the liver.  These changes 
may be related to FGFR4 inhibition, which is known to result in increases in liver function tests 
without histological correlates (Pai et al 2012). 
In the 28-day study in rats, no severe toxicity was observed; the no-observed-adverse-effect level 
(NOAEL) was determined as 1.05 mg/kg per day (6.3 mg/m2 per day), the highest dose tested.  
The human equivalent dose (HED) associated with 1.05 mg/kg per day based on standard body 
surface area conversion is 10.1 mg, and one-tenth of this dose is 1.01 mg.  In the 28-day monkey 
study, no severe toxicity was observed.  The NOAEL was considered to be 1 mg/kg per day 
(12 mg/m2 per day), the highest dose tested.  The HED associated with 1 mg/kg per day based on 
standard body surface area conversion is 19.2 mg; one-sixth of this dose is 3.2 mg.  Taking a 
conservative approach and using one-tenth the NOAEL in the more sensitive species (rat), 1 mg 
is proposed as the starting clinical dose for Part 1. 
It is estimated that a dose of 6 mg (QD) with an AUC of approximately 0.63 μM·h (≈ 0.06 μM·h, 
unbound) will be needed to exceed the IC50 at trough which has been shown to be efficacious in 
preclinical tumor models.  The AUC at the proposed starting clinical dose of 1 mg is estimated to 
be approximately 0.1 μM·h (≈ 0.01 μM·h, unbound).  The unbound AUC at the proposed starting 
dose is approximately 14-fold lower (monkey) and approximately 11-fold lower (male rats) than 
the unbound AUC values for the NOAELs determined in the 28-day GLP studies. 
1.4.2. 
Potential Risks of INCB054828 Based on Clinical Experience 
The comprehensive safety data that are included in IB Edition 5 used a data cutoff of 
25 NOV 2018.  As of the data cutoff date, a total of 562 participants (78 healthy participants and 
484 participants with advanced malignancies) were enrolled in the ongoing clinical studies and 
received at least 1 dose of pemigatinib.  Based on preliminary unaudited data from these ongoing 
studies, the most frequently occurring TEAEs (ie, incidence > 20%) were (in descending order of 
frequency) hyperphosphatemia, diarrhea, alopecia, fatigue, dry mouth, stomatitis, constipation, 
dysgeusia, nausea, decreased appetite, and anemia.  Additional details for the current study 
INCB 54828-101 are presented in the following section. 


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1.4.2.1. 
Study INCB 54828-101 
Of the 150 participants with advanced malignancies who have been enrolled in 
Study INCB 54828-101 as of the data cutoff date, 43 participants have been administered 
pemigatinib in Part 1 (monotherapy dose escalation), 63 participants in Part 2 (monotherapy dose 
expansion), and 44 participants in Part 3 (pemigatinib combined with gemcitabine and cisplatin 
[8 participants], docetaxel [7 participants], pembrolizumab [23 participants], and trastuzumab 
[6 participants]). 
Dose-limiting toxicities informed dose escalation procedures during Part 1 of the study.  Among 
participants in Part 1, 28 received pemigatinib at doses of 1 to 20 mg QD on a 
2-weeks-on/1-week-off therapy schedule (ie, interval dose regimen), and 15 participants received 
pemigatinib at doses of 9, 13.5, or 20 mg QD on a continuous schedule (ie, continuous dose 
regimen).  There were no DLTs for the monotherapy dose regimens, and the monotherapy MTD 
was not reached.  The recommended Part 2 dose for pemigatinib was determined to be 13.5 mg 
based on PD and clinical effect, and the recommended Phase 2 dose regimens for pemigatinib 
based on safety and PK data and preliminary signals of clinical benefit (data not shown) were 
13.5 mg QD following the interval schedule and 13.5 mg QD following the continuous schedule. 
Overall, 105 participants (99.1%) who received pemigatinib monotherapy (all doses and dose 
regimens combined) in Study INCB 54828-101 had TEAEs.  Treatment-emergent AEs occurring 
in ≥ 10% of participants who received pemigatinib monotherapy (Parts 1 and 2 combined) are 
presented by dose and dose regimen and overall in Table 1.  Consistent with the expected 
pharmacological effect of FGFR inhibition on serum phosphate levels, the most frequently 
occurring TEAE was hyperphosphatemia (74 participants [69.8%]; serum phosphate 
> 5.5 mg/dL).  Other frequent TEAEs (> 30%) included fatigue in 43 participants (40.6%), dry 
mouth in 39 participants (36.8%), and alopecia in 35 participants (33.0%).  Comparison of the 
most frequently occurring TEAEs for the continuous and interval dose regimens suggests higher 
incidences of hyperphosphatemia (76.7% vs 67.1%), stomatitis (46.7% vs 22.4%), dry mouth 
(43.3% vs 34.2%), diarrhea (43.3% vs 22.4%), constipation (40.0% vs 25.0%), alopecia (40.0% 
vs 30.3%), and nausea (33.3% vs 22.4%) with continuous dosing.  Other TEAEs that occurred 
more frequently with continuous dosing included dry eye, pain in extremity, hypercalcemia, 
onycholysis, and paronychia. 
Forty-five participants (42.5%) who received pemigatinib monotherapy had at least 1 SAE; the 
overall incidence of SAEs for the continuous dose regimen (56.7%) was higher than was seen for 
the interval dose regimen (36.8%).  Pneumonia in 7 participants (6.6%) was the most frequently 
occurring SAE.  Other SAEs occurring in more than 1 participant included back pain and disease 
progression in 4 participants (3.8%) each; abdominal pain, dehydration, fatigue, hyponatremia, 
and acute renal failure in 3 participants (2.8%) each; and blood bilirubin increased, 
cerebrovascular accident, constipation, hypotension, pain in extremity, pleural effusion, and 
pyrexia in 2 participants (1.9%) each.  Within the eye disorders SOC, a single participant had an 
SAE of ocular hyperemia (Grade 2), which was considered unrelated to pemigatinib by the 
investigator. 
A total of 11 participants (10.4%), 7 participants (9.2%) on an interval dose regimen and 
4 participants (13.3%) on a continuous dose regimen, had SAEs with a fatal outcome:  disease 
progression in 4 participants (3.8%) and pneumonia, malignant neoplasm progression (ie, disease 
progression), cerebrovascular accident, intracranial hemorrhage, multiorgan failure, esophageal 


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varices hemorrhage, pneumonia, respiratory failure, and acute respiratory failure secondary to 
acute anemia (verbatim term) in 1 participant (0.9%) each.  None of these fatal events were 
assessed as related to pemigatinib by the investigator. 
Eleven participants (10.4%) discontinued pemigatinib monotherapy due to TEAEs; pneumonia 
in 3 participants (2.8%) and dehydration and small intestinal obstruction in 2 participants (1.9%) 
each were the only TEAEs leading to discontinuation of pemigatinib that occurred in more than 
1 participant. 
More detailed information about the known and expected benefits and risks (clinical safety and 
nonclinical toxicology) and reasonably expected AEs of pemigatinib are provided in the IB. 
 


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Table 1: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 10% of Participants on Pemigatinib 
Monotherapy in Study INCB 54828-101 (Parts 1 and 2 Combined) in Decreasing Order of Frequency 
MedDRA Preferred Term, n (%) 
Pemigatinib Interval Dose Regimena 
Pemigatinib Continuous Dose Regimenb 
Total 
(N = 106) 
1/2/4 mg 
(N = 3) 
6 mg 
(N = 4) 
9 mg 
(N = 13) 
13.5 mg 
(N = 50) 
20 mg  
(N = 6) 
Subtotal 
(N = 76) 
9 mg 
(N = 8) 
13.5 mg  
(N = 16) 
20 mg  
(N = 6) 
Subtotal 
(N = 30) 
Hyperphosphataemia 
0 
1 (25.0) 
8 (61.5) 
38 (76.0) 
4 (66.7) 
51 (67.1) 
4 (50.0) 
14 (87.5) 
5 (83.3) 
23 (76.7) 
74 (69.8) 
Fatigue 
1 (33.3) 
1 (25.0) 
7 (53.8) 
19 (38.0) 
2 (33.3) 
30 (39.5) 
5 (62.5) 
5 (31.3) 
3 (50.0) 
13 (43.3) 
43 (40.6) 
Dry mouth 
0 
1 (25.0) 
6 (46.2) 
17 (34.0) 
2 (33.3) 
26 (34.2) 
2 (25.0) 
7 (43.8) 
4 (66.7) 
13 (43.3) 
39 (36.8) 
Alopecia 
0 
0 
7 (53.8) 
15 (30.0) 
1 (16.7) 
23 (30.3) 
2 (25.0) 
7 (43.8) 
3 (50.0) 
12 (40.0) 
35 (33.0) 
Constipation 
0 
0 
3 (23.1) 
14 (28.0) 
2 (33.3) 
19 (25.0) 
3 (37.5) 
5 (31.3) 
4 (66.7) 
12 (40.0) 
31 (29.2) 
Stomatitis 
0 
0 
3 (23.1) 
11 (22.0) 
3 (50.0) 
17 (22.4) 
4 (50.0) 
7 (43.8) 
3 (50.0) 
14 (46.7) 
31 (29.2) 
Diarrhoea 
0 
1 (25.0) 
2 (15.4) 
12 (24.0) 
2 (33.3) 
17 (22.4) 
1 (12.5) 
8 (50.0) 
4 (66.7) 
13 (43.3) 
30 (28.3) 
Nausea 
1 (33.3) 
1 (25.0) 
5 (38.5) 
8 (16.0) 
2 (33.3) 
17 (22.4) 
2 (25.0) 
7 (43.8) 
1 (16.7) 
10 (33.3) 
27 (25.5) 
Decreased appetite 
0 
2 (50.0) 
2 (15.4) 
12 (24.0) 
1 (16.7) 
17 (22.4) 
0 
4 (25.0) 
2 (33.3) 
6 (20.0) 
23 (21.7) 
Dysgeusia 
1 (33.3) 
0 
5 (38.5) 
8 (16.0) 
2 (33.3) 
16 (21.1) 
1 (12.5) 
3 (18.8) 
3 (50.0) 
7 (23.3) 
23 (21.7) 
Anaemia 
1 (33.3) 
0 
3 (23.1) 
10 (20.0) 
2 (33.3) 
16 (21.1) 
3 (37.5) 
2 (12.5) 
1 (16.7) 
6 (20.0) 
22 (20.8) 
Abdominal pain 
0 
0 
3 (23.1) 
11 (22.0) 
1 (16.7) 
15 (19.7) 
1 (12.5) 
4 (25.0) 
1 (16.7) 
6 (20.0) 
21 (19.8) 
Vomiting 
1 (33.3) 
0 
4 (30.8) 
8 (16.0) 
1 (16.7) 
14 (18.4) 
1 (12.5) 
2 (12.5) 
2 (33.3) 
5 (16.7) 
19 (17.9) 
Aspartate aminotransferase increased 
1 (33.3) 
0 
4 (30.8) 
7 (14.0) 
0 
12 (15.8) 
2 (25.0) 
4 (25.0) 
0 
6 (20.0) 
18 (17.0) 
Hypophosphataemia 
0 
0 
2 (15.4) 
10 (20.0) 
1 (16.7) 
13 (17.1) 
0 
4 (25.0) 
1 (16.7) 
5 (16.7) 
18 (17.0) 
Dehydration 
1 (33.3) 
1 (25.0) 
0 
7 (14.0) 
1 (16.7) 
10 (13.2) 
2 (25.0) 
2 (12.5) 
1 (16.7) 
5 (16.7) 
15 (14.2) 
Dry eye 
0 
0 
1 (7.7) 
7 (14.0) 
1 (16.7) 
9 (11.8) 
0 
5 (31.3) 
1 (16.7) 
6 (20.0) 
15 (14.2) 
Pain in extremity 
0 
1 (25.0) 
3 (23.1) 
3 (6.0) 
1 (16.7) 
8 (10.5) 
1 (12.5) 
5 (31.3) 
1 (16.7) 
7 (23.3) 
15 (14.2) 
Alanine aminotransferase increased 
1 (33.3) 
0 
4 (30.8) 
4 (8.0) 
0 
9 (11.8) 
2 (25.0) 
3 (18.8) 
0 
5 (16.7) 
14 (13.2) 
Cough 
1 (33.3) 
0 
1 (7.7) 
6 (12.0) 
2 (33.3) 
10 (13.2) 
1 (12.5) 
3 (18.8) 
0 
4 (13.3) 
14 (13.2) 
Vision blurred 
1 (33.3) 
1 (25.0) 
2 (15.4) 
4 (8.0) 
2 (33.3) 
10 (13.2) 
0 
3 (18.8) 
1 (16.7) 
4 (13.3) 
14 (13.2) 
Weight decreased 
2 (66.7) 
0 
2 (15.4) 
5 (10.0) 
2 (33.3) 
11 (14.5) 
1 (12.5) 
0 
2 (33.3) 
3 (10.0) 
14 (13.2) 
Blood alkaline phosphatase increased 
1 (33.3) 
0 
3 (23.1) 
6 (12.0) 
0 
10 (13.2) 
2 (25.0) 
1 (6.3) 
0 
3 (10.0) 
13 (12.3) 
Hypercalcaemia 
1 (33.3) 
0 
1 (7.7) 
5 (10.0) 
0 
7 (9.2) 
2 (25.0) 
3 (18.8) 
1 (16.7) 
6 (20.0) 
13 (12.3) 
Back pain 
1 (33.3) 
0 
4 (30.8) 
4 (8.0) 
0 
9 (11.8) 
1 (12.5) 
2 (12.5) 
0 
3 (10.0) 
12 (11.3) 
Onycholysis 
0 
0 
1 (7.7) 
5 (10.0) 
0 
6 (7.9) 
1 (12.5) 
5 (31.3) 
0 
6 (20.0) 
12 (11.3) 
Paronychia 
0 
0 
1 (7.7) 
2 (4.0) 
2 (33.3) 
5 (6.6) 
1 (12.5) 
4 (25.0) 
2 (33.3) 
7 (23.3) 
12 (11.3) 
Arthralgia 
0 
1 (25.0) 
3 (23.1) 
2 (4.0) 
2 (33.3) 
8 (10.5) 
0 
2 (12.5) 
1 (16.7) 
3 (10.0) 
11 (10.4) 
Hyponatraemia 
0 
0 
1 (7.7) 
5 (10.0) 
1 (16.7) 
7 (9.2) 
0 
3 (18.8) 
1 (16.7) 
4 (13.3) 
11 (10.4) 
Nail discolouration 
0 
0 
2 (15.4) 
5 (10.0) 
0 
7 (9.2) 
1 (12.5) 
2 (12.5) 
1 (16.7) 
4 (13.3) 
11 (10.4) 
Note:  Participants were counted once under each MedDRA preferred term.  Adverse events are ordered by the descending frequency in the total column. 
Note:  Treatment-emergent AEs are any AEs either reported for the first time or worsening of a pre-existing event after first dose of study drug. 
a Pemigatinib was administered QD on a 2-weeks-on/1-week-off therapy schedule. 
b Pemigatinib was administered QD. 


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Treatment-emergent AEs occurring in ≥ 10% of participants on combination therapy in 
Study INCB 54828-101 (Part 3) are presented by treatment group and overall in Table 2.  The 
most frequently occurring TEAEs for each treatment combination were as follows: 
• Pemigatinib + Gemcitabine + Cisplatin:  Anemia (8/8 participants); blood 
creatinine increased, constipation, fatigue, and nausea (5/8 participants each); and 
ALT increased, AST increased, diarrhea, hyperphosphatemia, hyponatremia, 
thrombocytopenia, and WBC count decreased (4/8 participants each). 
• Pemigatinib + Docetaxel:  Hyperphosphatemia, diarrhea, and dysgeusia 
(6/7 participants each); fatigue and dehydration (5/7 participants each); and nausea 
(4/7 participants). 
• Pemigatinib + Pembrolizumab:  Hyperphosphatemia (17/23 participants), anemia 
(11/23 participants), and diarrhea and decreased appetite (10/23 participants each). 
• Pemigatinib + Trastuzumab:  Alopecia, cough, and hyperphosphatemia 
(4/6 participants each) and decreased appetite, diarrhea, and dry mouth 
(3/6 participants each). 
A single participant who received pemigatinib + docetaxel had DLTs of fatigue (Grade 3) and 
dehydration (Grade 3).  No other participants on combination therapy had a DLT.   
A total of 18 participants (40.9%) on combination therapy had at least 1 SAE:  4/8 participants 
on pemigatinib + gemcitabine + cisplatin, 6/7 participants on pemigatinib + docetaxel, and 
8/23 participants on pemigatinib + pembrolizumab.  The most frequently occurring SAEs across 
all combination therapy cohorts were dehydration in 3 participants (6.8%) and anemia and acute 
renal failure in 2 participants (4.5%) each.  By treatment combination, the only SAE occurring in 
more than 1 participant was dehydration in 2 participants in the pemigatinib + docetaxel cohort.  
Two participants (4.5%) had SAEs with a fatal outcome:  completed suicide (pembrolizumab + 
pemigatinib 9 mg) and disease progression (gemcitabine + cisplatin + pemigatinib 13.5 mg).  
Neither of these events was assessed as related to pemigatinib. 
Five participants (11.4%) on combination therapy had TEAEs leading to discontinuation of 
pemigatinib.  No event leading to discontinuation occurred in more than 1 participant. 


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Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 10% of Participants on Pemigatinib 
Combination Therapy in Study INCB 54828-101 (Part 3) in Decreasing Order of Frequency 
MedDRA Preferred Term, n (%) 
Pemigatinib 
+ GEM + CIS 
Pemigatinib 
 + DOC 
Pemigatinib + PEM 
Pemigatinib 
+ TRAS 
Total 
(N = 44) 
Interval Dose 
Regimena 
Interval 
Dose 
Regimena 
Interval Dose Regimena 
Continuous 
Dose 
Regimenb 
Interval Dose 
Regimena 
9 mg 
(N = 1) 
13.5 mg 
(N = 7) 
13.5 mg 
(N = 7) 
9 mg 
(N = 3) 
13.5 mg  
(N = 14) 
Subtotal 
(N = 17) 
13.5 mg 
(N = 6) 
13.5 mg 
(N = 6) 
Hyperphosphataemia 
1 (100.0) 
3 (42.9) 
6 (85.7) 
3 (100.0) 
11 (78.6) 
14 (82.4) 
3 (50.0) 
4 (66.7) 
31 (70.5) 
Anaemia 
1 (100.0) 
7 (100.0) 
3 (42.9) 
1 (33.3) 
8 (57.1) 
9 (52.9) 
2 (33.3) 
2 (33.3) 
24 (54.5) 
Diarrhoea 
0 
4 (57.1) 
6 (85.7) 
1 (33.3) 
7 (50.0) 
8 (47.1) 
2 (33.3) 
3 (50.0) 
23 (52.3) 
Fatigue 
0 
5 (71.4) 
5 (71.4) 
1 (33.3) 
5 (35.7) 
6 (35.3) 
1 (16.7) 
2 (33.3) 
19 (43.2) 
Alopecia 
0 
1 (14.3) 
3 (42.9) 
0 
6 (42.9) 
6 (35.3) 
2 (33.3) 
4 (66.7) 
16 (36.4) 
Constipation 
1 (100.0) 
4 (57.1) 
3 (42.9) 
0 
5 (35.7) 
5 (29.4) 
1 (16.7) 
2 (33.3) 
16 (36.4) 
Decreased appetite 
0 
2 (28.6) 
1 (14.3) 
0 
9 (64.3) 
9 (52.9) 
1 (16.7) 
3 (50.0) 
16 (36.4) 
Dry mouth 
1 (100.0) 
2 (28.6) 
1 (14.3) 
0 
4 (28.6) 
4 (23.5) 
4 (66.7) 
3 (50.0) 
15 (34.1) 
Dysgeusia 
0 
2 (28.6) 
6 (85.7) 
0 
3 (21.4) 
3 (17.6) 
3 (50.0) 
1 (16.7) 
15 (34.1) 
Nausea 
1 (100.0) 
4 (57.1) 
4 (57.1) 
0 
3 (21.4) 
3 (17.6) 
1 (16.7) 
2 (33.3) 
15 (34.1) 
Stomatitis 
1 (100.0) 
2 (28.6) 
2 (28.6) 
1 (33.3) 
5 (35.7) 
6 (35.3) 
1 (16.7) 
2 (33.3) 
14 (31.8) 
Blood creatinine increased 
1 (100.0) 
4 (57.1) 
1 (14.3) 
1 (33.3) 
4 (28.6) 
5 (29.4) 
0 
1 (16.7) 
12 (27.3) 
Dehydration 
1 (100.0) 
2 (28.6) 
5 (71.4) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
1 (16.7) 
0 
12 (27.3) 
Aspartate aminotransferase increased 
0 
4 (57.1) 
0 
0 
5 (35.7) 
5 (29.4) 
1 (16.7) 
1 (16.7) 
11 (25.0) 
Cough 
0 
1 (14.3) 
1 (14.3) 
0 
5 (35.7) 
5 (29.4) 
0 
4 (66.7) 
11 (25.0) 
Alanine aminotransferase increased 
0 
4 (57.1) 
0 
0 
5 (35.7) 
5 (29.4) 
1 (16.7) 
0 
10 (22.7) 
Dyspnoea 
0 
2 (28.6) 
0 
1 (33.3) 
4 (28.6) 
5 (29.4) 
1 (16.7) 
2 (33.3) 
10 (22.7) 
Vomiting 
0 
3 (42.9) 
3 (42.9) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
1 (16.7) 
0 
10 (22.7) 
Dry eye 
0 
0 
1 (14.3) 
0 
4 (28.6) 
4 (23.5) 
2 (33.3) 
2 (33.3) 
9 (20.5) 
Hyponatraemia 
1 (100.0) 
3 (42.9) 
2 (28.6) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
0 
0 
9 (20.5) 
Hypomagnesaemia 
1 (100.0) 
1 (14.3) 
1 (14.3) 
1 (33.3) 
4 (28.6) 
5 (29.4) 
0 
0 
8 (18.2) 
Abdominal pain 
1 (100.0) 
1 (14.3) 
1 (14.3) 
0 
2 (14.3) 
2 (11.8) 
2 (33.3) 
0 
7 (15.9) 
Back pain 
0 
0 
2 (28.6) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
1 (16.7) 
1 (16.7) 
7 (15.9) 
Blood alkaline phosphatase increased 
0 
1 (14.3) 
1 (14.3) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
1 (16.7) 
1 (16.7) 
7 (15.9) 
Hypercalcaemia 
0 
1 (14.3) 
1 (14.3) 
1 (33.3) 
4 (28.6) 
5 (29.4) 
0  
0 
7 (15.9) 


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Table 2: 
Summary of Treatment-Emergent Adverse Events Occurring in ≥ 10% of Participants on Pemigatinib 
Combination Therapy in Study INCB 54828-101 (Part 3) in Decreasing Order of Frequency (Continued) 
MedDRA Preferred Term, n (%) 
Pemigatinib 
+ GEM + CIS 
Pemigatinib 
 + DOC 
Pemigatinib + PEM 
Pemigatinib 
+ TRAS 
Total 
(N = 44) 
Interval Dose 
Regimena 
Interval 
Dose 
Regimena 
Interval Dose Regimena 
Continuous 
Dose 
Regimenb 
Interval Dose 
Regimena 
9 mg 
(N = 1) 
13.5 mg 
(N = 7) 
13.5 mg 
(N = 7) 
9 mg 
(N = 3) 
13.5 mg  
(N = 14) 
Subtotal 
(N = 17) 
13.5 mg 
(N = 6) 
13.5 mg 
(N = 6) 
Hypoalbuminaemia 
1 (100.0) 
0 
1 (14.3) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
0 
1 (16.7) 
6 (13.6) 
Hypokalaemia 
1 (100.0) 
2 (28.6) 
0 
0 
3 (21.4) 
3 (17.6) 
0 
0 
6 (13.6) 
Hypotension 
0 
0 
2 (28.6) 
1 (33.3) 
3 (21.4) 
4 (23.5) 
0 
0 
6 (13.6) 
Neutropenia 
0 
3 (42.9) 
3 (42.9) 
0 
0 
0 
0 
0 
6 (13.6) 
Pyrexia 
1 (100.0) 
0 
0 
0 
1 (7.1) 
1 (5.9) 
2 (33.3) 
2 (33.3) 
6 (13.6) 
Vision blurred 
0 
1 (14.3) 
1 (14.3) 
0 
3 (21.4) 
3 (17.6) 
0 
1 (16.7) 
6 (13.6) 
Dizziness 
0 
3 (42.9) 
0 
0 
2 (14.3) 
2 (11.8) 
0 
0 
5 (11.4) 
Headache 
0 
1 (14.3) 
1 (14.3) 
0 
1 (7.1) 
1 (5.9) 
0 
2 (33.3) 
5 (11.4) 
Hyperglycaemia 
0 
1 (14.3) 
1 (14.3) 
1 (33.3) 
2 (14.3) 
3 (17.6) 
0 
0 
5 (11.4) 
Oedema peripheral 
0 
1 (14.3) 
2 (28.6) 
0 
1 (7.1) 
1 (5.9) 
1 (16.7) 
0 
5 (11.4) 
Paronychia 
0 
0 
2 (28.6) 
0 
2 (14.3) 
2 (11.8) 
0 
1 (16.7) 
5 (11.4) 
White blood cell count decreased 
1 (100.0) 
3 (42.9) 
0 
0 
1 (7.1) 
1 (5.9) 
0 
0 
5 (11.4) 
Weight decreased 
0 
1 (14.3) 
3 (42.9) 
0 
0 
0 
1 (16.7) 
0 
5 (11.4) 
CIS = cisplatin; DOC = docetaxel; GEM = gemcitabine; PEM = pembrolizumab; TRAS = trastuzumab. 
Note:  Participants were counted once under each MedDRA preferred term.  Adverse events are ordered by the descending frequency in total column. 
Note:  Treatment-emergent AEs are any AEs either reported for the first time or worsening of a pre-existing event after first dose of study drug. 
a Pemigatinib was administered QD on a 2-weeks-on/1-week-off therapy schedule. 
b Pemigatinib was administered QD. 


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1.4.2.2. 
Pharmacokinetic/Pharmacodynamic Summary 
Following QD oral doses of INCB054828 on a 2-weeks-on/1-week-off dosing schedule, an 
approximately linear relationship was observed for INCB054828 exposure (Cmax and AUC) over 
the dose range studied in Study INCB 52828-101 (1 to 20 mg).  INCB054828 is rapidly 
absorbed, attaining peak plasma concentrations in approximately 1 to 2 hours after oral 
administration, and the geometric mean t½ is 15.4 hours.  At the 13.5 mg QD dose, geometric 
mean of steady-state Cmax value is 236 nM and AUC0-24 is 2620 nM·h, the geometric mean 
steady-state oral clearance of INCB054828 is low (10.6 L/h), and apparent steady-state volume 
of distribution is moderate (235 L).  The PK parameters for continuous administration are similar 
to those for intermittent dosing.  The projected average inhibition of FGFR2 based on PK and in 
vitro potency of INCB054828 ranged from 41% at 1 mg to 97% at 20 mg.  Consistent with this 
projection, the observed inhibition of pFGFR2 in KATOIII cells spiked to ex vivo whole blood 
samples collected from subjects at trough was 82% after the 13.5 mg QD dose and 64% after the 
9 mg QD dose.  The steady-state plasma concentrations of INCB054828 after 13.5 mg QD dose 
that exceeded in vivo IC50 over a 24-hour dosing period is showed in Figure 1.  The magnitude 
and frequency of HP was also dose-dependent.  In the 9-mg cohort, 1 of 3 subjects developed HP 
in Part 1; 3 additional subjects were enrolled at 9 mg in Part 2.  Of a total of 6 subjects 
administered 9 mg, 4 experienced HP; in the 13.5-mg cohort, all 6 subjects developed HP, which 
was managed with a low-phosphate diet and introduction of phosphate binders.  Further, the 
increase in serum phosphorus observed after treatment with INCB054828 was exposure-
dependent (see Figure 2). 
Figure 1: 
INCB054828 Plasma Concentrations (Mean ± SE) at Steady State Following 
Once-Daily Dosing of Pemigatinib as Monotherapy 
 


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Figure 2: 
Serum Phosphate Versus Exposure 
 
Subjects will be monitored on an ongoing basis throughout this study as per the schedule of 
laboratory assessments (see Table 20). 
1.4.3. 
Potential Risks of Gemcitabine and Cisplatin 
Gemcitabine is a nucleoside analog with structural similarity to cytarabine and is currently 
approved to treat breast cancer, NSCLC, ovarian cancer, and pancreatic cancer either alone or in 
combination with other chemotherapy agents. 
Cisplatin is a platinum-containing alkylating agent and is currently approved to treat ovarian 
germ cell cancer, invasive bladder cancer, ovarian cancer, and testicular germ cell cancer either 
alone or in combination with other chemotherapy agents. 
The combination of gemcitabine and cisplatin are indicated for use in the treatment of biliary 
tract cancer, bladder cancer, cervical cancer, malignant mesothelioma, NSCLC, ovarian cancer, 
and pancreatic cancer and are also being investigated in treating other cancers 
Risks associated with use of gemcitabine include myelosuppression, which is the principal DLT.  
Gemcitabine can suppress bone marrow function as manifested by leukopenia, 
thrombocytopenia, and anemia.  Subjects should be monitored for myelosuppression during 
therapy.  The most common adverse reactions as a monotherapy are nausea; vomiting; anemia; 
increased ALT, AST, and alkaline phosphatase (ALP); neutropenia; leukopenia; proteinuria; 
fever; hematuria; rash; thrombocytopenia; and dyspnea.  A complete discussion of risks 
associated with gemcitabine can be found in the United States Package Insert (USPI) or in the 
Summary of Product Characteristics (SmPC). 
The following cisplatin side effects are common (occurring in > 30%):  nausea, vomiting, kidney 
toxicity (dose related and typically reversible), neutropenia, leukopenia, and anemia.  Less 
common side effects (occurring in 10-29%) include the following:  peripheral neuropathy; 
paresthesia; sensory loss; numbness and tingling; difficulty walking (some effects may be 
irreversible); tinnitus; anorexia; dysgeusia; increased ALT, AST, and ALP; and alopecia.  
A complete and detailed list of risks associated with cisplatin use can be found in the USPI or 
SmPC. 


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1.4.4. 
Potential Risks of Docetaxel 
Docetaxel is an antimitotic chemotherapy medication that works by interfering with cell division 
and is a member of the taxane class of drugs.  It is indicated for use in subjects with breast 
cancer, NSCLC, prostate cancer, gastric cancer, bladder cancer, and head and neck cancer. 
The most serious adverse reactions from docetaxel are toxic deaths, hepatotoxicity, neutropenia, 
hypersensitivity, and fluid retention.  These are noted in the black box warning on the product 
label. 
The reporting and incidence of AEs associated with docetaxel vary by dose and by indication; 
however, the most common adverse reactions across all docetaxel indications are infections, 
neutropenia, anemia, febrile neutropenia, hypersensitivity, thrombocytopenia, neuropathy, 
dysgeusia, dyspnea, constipation, anorexia, nail disorders, fluid retention, asthenia, pain, nausea, 
diarrhea, vomiting, mucositis, alopecia, skin reactions, and myalgia.  A complete and detailed list 
of risks associated with docetaxel use can be found in the USPI or in the SmPC. 
1.4.5. 
Potential Risks of Pembrolizumab 
Pembrolizumab is a PD-1 inhibitor that works by blocking the inhibitory ligand of programmed 
cell death 1 receptor.  It is part of a class of drug called the immune checkpoint inhibitors. 
The following immune-mediated adverse reactions have been reported with use of 
pembrolizumab (2mg/kg):  pneumonitis, colitis, hepatitis, endocrinopathies, renal failure, and 
nephritis.  Additional notable (>30%) drug-related AEs (all grades) reported include fatigue, 
nausea, cough, pruritus, anemia, hyperglycemia, hyponatremia, and hypoalbuminemia.  
A complete and detailed list of risks associated with pembrolizumab use can be found in the 
USPI or in the SmPC. 
1.4.6. 
Potential Risks of Trastuzumab 
Trastuzumab is a humanized monoclonal antibody that selectively binds to the extracellular 
domain of the human epidermal growth factor receptor 2 protein, HER2. 
The most significant AE observed in subjects who receive trastuzumab is cardiac dysfunction, 
reflected by asymptomatic decreases in left ventricular ejection fraction (LVEF) and, less 
frequently, by clinically symptomatic congestive heart failure.  Risk factors for cardiac failure in 
the setting of trastuzumab treatment include coadministration with anthracycle-based 
chemotherapy, increasing age, a declining LVEF during treatment to below the lower limit of 
normal, and the use of antihypertensive medications (Tan-Chiu 2005).  Subjects receiving 
trastuzumab should undergo frequent monitoring of cardiac function.  Discontinuation of 
trastuzumab therapy should be strongly considered in subjects who develop clinically significant 
congestive heart failure.  Refer to the USPI or the SmPC for more information. 


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1.4.7. 
Potential Risks of INCMGA00012 
INCMGA00012 is an IgG4 humanized mAb that has been designed to restore T-cell immune 
function, similar to other PD-1 inhibitors that have been extensively studied.  Therefore, safety 
experience with other drugs should be considered when administering INCMGA00012.  
Potentially serious irAEs include: 
• Pneumonitis 
• Hepatitis 
• Colitis 
• Nephritis 
• Endocrinopathies (thyroiditis, hypophysitis, Type I diabetes) 
• Encephalitis 
• Myocarditis 
• Skin reactions (including Stevens-Johnson Syndrome/toxic epidermal necrolysis) 
• Rejection of organ transplants 
Other reactions (including arthritis, uveitis, myositis, Guillain-Barré syndrome, myasthenia 
gravis, vasculitis, pancreatitis, and hemolytic anemia). 
The occurrence of any of these syndromes may dictate interruption and potential discontinuation 
of study drug administration pending further evaluation, and reporting them to the sponsor as 
AEs of special interest.  Most low-grade immune-related AEs (irAEs) can be managed 
symptomatically.  Persistent low-grade or moderate toxicities may require treatment with 
corticosteroids or, in refractory cases, other immune suppressing agents such as mycophenolate 
or infliximab.  High-grade immune-related toxicities will, in almost all cases, require treatment 
with corticosteroids. 
Temporary interruptions of INCMGA00012 may be required in the event of treatment-related 
immune-related toxicity.  General guidelines for specific toxicity regarding dosing and treatment 
are provided in Section 5.8.6.  All toxicities will be graded according to NCI CTCAE v4.03. 
1.4.8. 
Potential Risks Related to the Combination Regimens 
The effects of concomitant INCB054828 with gemcitabine + cisplatin, docetaxel, 
pembrolizumab, trastuzumab, or INCMGA00012 are being assessed in this Protocol.  As 
described above, the most common AEs associated with these medications are neutropenia, 
anemia, thrombocytopenia, cardiac dysfunction, and immune-related events.  The most common 
AE associated with INCB054828 has been HP.  There is not an expected overlap or interaction 
between these profiles.  Hematology and blood chemistry parameters will be closely monitored 
in all study subjects.  In addition, all AEs will be monitored to identify occurrences of new safety 
signals or potentiation of any gemcitabine-related, cisplatin-related, docetaxel-related, 
pembrolizumab-related, trastuzumab-related, or INCMGA00012-related sided effects. 


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1.5. 
Justification of Route, Dose Regimen, and Treatment Period 
1.5.1. 
INCB054828 
INCB054828 is being developed as a new investigational drug for oral administration.  Oral drug 
administration is generally the most convenient and cost-effective method of drug delivery for 
medications requiring continuous exposure.  INCB054828 tablets will be administered orally QD 
on a 2-week on-therapy and 1-week off-therapy schedule, a continuous dosing schedule, and for 
a small subset of subjects a twice daily (BID) continuous dosing schedule.  One cycle will be 
defined as 21 continuous days; treatment for subjects in this study will consist of repeating 
21-day cycles (ie, 14 days on therapy and 7 days off therapy).  Justification for the initial  dose 
regimen (2 weeks on and 1 week off) came from a preclinical toxicology study in rats where 
INCB054828 was administered daily for 14 days followed by a 7-day nontreatment period.  
Additionally, INCB054828 was well tolerated in all dose levels tested in a 28-day continuous 
treatment toxicology study in cynomolgus monkeys. 
Based on preclinical data, the terminal elimination half-life of INCB054828 in humans is 
projected to be approximately 16 hours.  A clinical dose of 6 mg QD is estimated to provide a 
Cave of approximately 0.025 μM, which is roughly twice the whole blood IC50 (0.011 μM).  
Following a 6 mg QD dose, the steady-state plasma AUC is estimated to be approximately 
0.6 μM·h, the Cmax is estimated to be approximately 0.05 μM, and the Cmin is expected to exceed 
the whole blood IC50.  Preclinical data suggest that the whole blood IC90 for INCB054828 is 
approximately 0.077 μM.  Thus, it is reasonable to expect that full pharmacologic inhibition can 
be achieved with INCB054828 at a feasible clinical dose. 
Based on the findings in preclinical toxicology experiments in rats and monkeys, HP, physeal 
dysplasia, and soft tissue mineralization are toxicities of concern.  These toxicities have been 
reported in rodents and large animals following administration of selective FGFR inhibitors and 
can be explained by the pharmacological action of FGFR inhibition.  Data from ongoing clinical 
studies of selective FGFR inhibitors have confirmed that HP is an on-target pharmacologic effect 
of FGFR inhibition, and that it can be managed with phosphate-binding therapy, dose 
interruptions, and dose reductions.  Clear guidance for the management of HP has been provided 
in this Protocol to initiate a low-phosphate diet, phosphate-binding therapy, phosphaturic agents, 
and dose interruptions and reductions depending on the serum phosphate level, which will be 
monitored weekly (at least twice weekly if abnormal).  Additional safety measures have been 
added to the Protocol to require regular ophthalmological examinations and to exclude subjects 
with a history of a calcium/phosphate homeostasis disorder, a history and/or current evidence of 
ectopic mineralization/calcification, or current evidence of corneal disorder/keratopathy and 
retinal disorders. 
Based on preclinical toxicology, the highest non–severely toxic dose in the most sensitive 
species is 1.05 mg/kg per day (6.3 mg/m2 per day), the highest dose tested in the rat.  This 
produces a HED of 10.1 mg, and using a conservative approach, one-tenth of this dose is 
1.01 mg, thus the proposed starting dose is 1 mg. 
Dose escalation will be conducted in an accelerated titration design (approximately 1 subject per 
cohort) and will switch to a 3 + 3 design once a Grade 2 or greater toxicity or HP 
(serum phosphate > 5.5 mg/dL) is observed.  Subsequent cohorts will have increases in the dose 
of INCB054828 limited to no more than 50%. 


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An expansion (Part 2) of approximately 140 subjects with advanced malignancies that have 
genetic alterations in FGF or FGFR genes will be treated with the selected dose, either the MTD 
or the pharmacologically active dose (PAD) of INCB054828, to further determine safety, 
tolerability, efficacy, PK, food effect, and PD.  Once enrollment in the expansion begins, 
approximately 8 subjects will be evaluated in the food-effect study. 
The sponsor may implement alternate regimens such as intermediate doses or alternate 
administration schedules depending on PK, PD, and safety results. 
1.5.2. 
Continuous Administration of INCB054828 
1.5.2.1. 
Nonclinical 
The nonclinical toxicology program for INCB054828 was conducted to support clinical studies 
in subjects with cancer and was designed in accordance with ICH S9 (FDA 2010).  The studies 
successfully supported the selection of a safe starting dose and entry into the current Phase 1 
clinical study in subjects with cancer (INCB 54828-101).  The toxicology studies are outlined in 
Table 3 and detailed in IND 124358. 
Table 3: 
INCB054828 Toxicology Program 
Study Type (Compliance) and Duration 
Species/Test System 
Route of Administration 
Single-dose toxicity (non-GLP)  
Rat and monkey 
Oral gavage 
Repeat-dose toxicity (non-GLP)  
Daily for 9-10 days  
Rat and monkey 
Oral gavage 
Repeat-dose toxicity (GLP) 
 
 
Intermittent dosing:  14 days dosing followed by 
7 days nondosing followed by 14 days dosing 
Rat 
Oral gavage 
Daily for 28 days 
Monkey 
Oral gavage 
The target organ profile in both species was consistent with INCB054828 pharmacology 
(FGFR inhibition) and included hyperphosphatemia, physeal dysplasia, and soft tissue 
mineralization.  Mineralization was observed in numerous tissues and was not reversible 
(after 4-week recovery periods), while physeal and cartilage findings were reversible. 
At the NOAEL in the 28-day rat study, findings were minimal and considered to be exacerbation 
of normal background findings.  The rat NOAEL was associated with AUC0-24h values of 
2.88 and 3.39 μM∙h in males and females, respectively.  At the NOAEL in the 28-day monkey 
study, findings were limited to reversible, minimal to mild alterations in the femoral physis and 
sternal cartilage (synchondrosis).  The monkey NOAEL was associated with AUC0-24h values of 
1.78 and 1.65 μM∙h in males and females, respectively. 
The dose proposed for continuous (QD) dosing in INCB 54828-101 is 9 mg.  In subjects given 
this dose on an intermittent schedule (2 weeks on and 1 week off per cycle), the AUC0-τ was 
1.7 μM∙h; similar to the NOAEL-AUCs determined for rats administered study drug on an 
intermittent schedule and in monkeys administered study drug QD for 28 days. 


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1.5.2.2. 
Pharmacokinetics 
INCB054828 exhibits linear PK over the dose range examined to date (1-13.5 mg; PK data not 
yet available for 20 mg).  In both preclinical and clinical studies, change in serum phosphorus 
can be used as a surrogate marker for FGFR1 signaling.  In study INCB 54828-101, using the 
2-weeks-on and 1-week-off treatment schedule, increase in serum phosphorus is observed to be 
dose- as well as exposure-dependent (plasma AUC of INCB054828), with normalization 
occurring rapidly after treatment interruption (ie, it is readily reversible).  The increase in serum 
phosphorus is minimal at 6 mg QD, moderate at 9 mg QD, and more consistent at doses > 9 mg 
QD.  Based on these observations, 9 mg QD appears to be a PAD.  Further, the 2 objective 
clinical responses observed to date in study INCB 54828-101 were at the 9 mg QD dose level.  
Therefore, the proposed starting dose for continuous administration is 9 mg QD.  Serum 
phosphorus 
 will be monitored carefully, and the daily dose will be 
decreased if serum phosphorus is consistently elevated. 
1.5.3. 
Twice-Daily Administration of INCB054828 
Erdafitinib is an inhibitor of FGFR approved for treatment of bladder cancer.  The long effective 
half-life of erdafitinib (59 hours) in cancer patients predicts low steady-state peak-to-trough 
fluctuation for target (pFGFR2) inhibition (93.6%-95.1% at therapeutic dose of 9 mg QD; 
Table 4).  With administration of pemigatinib 13.5 mg QD, relatively high steady-state peak-to-
trough fluctuation for pFGFR2 inhibition (82.7%-96.2%; Table 4) is predicted due to the 
relatively short half-life of pemigatinib (15 hours) compared to erdafitinib.  Simulations suggest 
that BID administration of pemigatinib at a dose level above 9 mg can produce similar or higher 
pFGFR2 inhibition compared to erdafitinib 9 mg QD.  Therefore, BID dosing of pemigatinib is 
proposed to improve the efficacy of FGFR inhibition. 
Table 4: 
Comparison of Projected pFGFR2 Inhibition for Erdafitinib and 
Pemigatinib in Various Dose Regimens 
Drug/Dose Regimen 
Imax 
Iave 
Imin 
Erdacitinib 9 mg QD 
95.1% 
94.5% 
93.6% 
Pemigatinib 13.5 mg QD 
96.2% 
90.0% 
82.7% 
Pemigatinib 13.5 mg BID 
97.8% 
96.6% 
95.2% 
Pemigatinib 9 mg BID 
96.1% 
94.1% 
91.5% 
Pemigatinib 6 mg BID 
93.1% 
89.1% 
85.4% 
The target for the BID dosing schedule will be subjects with advanced/metastatic bladder cancer 
with FGFR3 alterations (mutations or fusions) in Part 2 (approximately 10 subjects). 
1.5.4. 
Gemcitabine + Cisplatin 
Gemcitabine + cisplatin combination regimen will be administered as open-label, commercially 
available product to be supplied by the clinical site.  Gemcitabine is typically administered 
intravenously at 1000 mg/m2 on Days 1, 8, and 15 of a 28-day cycle.  Since the cycle for 
INCB054828 is 21 days, gemcitabine will be administered on Days 1 and 8 of the 21-day cycle.  
Cisplatin will be administered intravenously at 70 mg/m2 once every 3 weeks on Day 1 of each 
21-day cycle.  Dose modifications can be made to manage toxicity. 


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1.5.5. 
Docetaxel 
Docetaxel will be administered as open-label, commercially available product to be supplied by 
the clinical site.  Docetaxel will be administered intravenously at a starting dose of 75 mg/m2 
once every 3 weeks on Day 1 of each 21-day cycle.  Dose modifications can be made to manage 
toxicity. 
1.5.6. 
Pembrolizumab 
The dose of pembrolizumab planned to be studied in this study is 200 mg every 3 weeks.  The 
dose recently approved in the United States for treatment of melanoma subjects is 2 mg/kg every 
3 weeks.  Information on the rationale for selecting 200 mg every 3 weeks is summarized below. 
An integrated body of evidence suggests that 200 mg every 3 weeks is expected to provide 
similar response to 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, and 10 mg/kg every 
2 weeks.  Previously, a flat pembrolizumab exposure-response relationship for efficacy and 
safety has been found in subjects with melanoma in the range of doses between 2 mg/kg and 
10 mg/kg.  Exposures for 200 mg every 3 weeks are expected to lie within this range and will be 
close to those obtained with 2 mg/kg every 3 weeks dose.  The 2 mg/kg every 3 weeks dose is 
the approved dose for metastatic melanoma in the United States. 
The PK profile of pembrolizumab is consistent with that of other humanized monoclonal 
antibodies, which typically have a low clearance and a limited volume of distribution.  The 
distribution of exposures from the 200 mg fixed dose is predicted to considerably overlap those 
obtained with the 2 mg/kg dose and, importantly, will maintain individual subject exposures 
within the exposure range established in melanoma as associated with maximal clinical response.  
The slight increase in PK variability predicted for the fixed dose relative to weight-based dose 
administration is not expected to be clinically important given that the range of individual 
exposures is well contained within the range of exposures shown in the melanoma studies of 
2 mg/kg and 10 mg/kg to provide similar efficacy and safety. 
In translating to other solid tumor indications, similarly flat exposure-response relationships for 
efficacy and safety as observed in subjects with melanoma can be expected, as the antitumor 
effect of pembrolizumab is driven through immune system activation rather than through a direct 
interaction with tumor cells, rendering it independent of the specific tumor type.  In addition, 
available PK results in subjects with melanoma, NSCLC, and other solid tumor types support a 
lack of meaningful difference in PK exposures obtained at tested doses among tumor types.  
Thus, the 200 mg every 3 weeks fixed dose regimen is considered an appropriate fixed dose for 
other solid tumor indications as well.  Dose modifications can be made to manage toxicity. 
1.5.7. 
Trastuzumab 
The initial approved dose of trastuzumab in breast cancer was 4 mg/kg initial dose followed by a 
2 mg/kg dose given every 7 days.  This regimen was based on clinical efficacy in a randomized 
Phase 3 study (Bang et al 2010).  Since the initial approval, the half-life of trastuzumab has been 
determined to be approximately 28.5 days, which supports administration every 3 weeks versus 
weekly.  The average exposure at any time during the treatment is comparable between the 
2 regimens.  The every-3-week regimen has been used in subjects with breast cancer as well as 
gastric cancer (refer to the USPI and SmPC). 


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1.5.8. 
INCMGA00012 
INCMGA00012 in combination with INCB054828 will be tested in this study.  A fixed dose of 
INCMGA00012 will be used.  Fixed doses have several advantages over weight-based doses, 
including convenience of preparation and administration, reducing errors in preparation 
calculation, and minimization of drug waste.  Body weight–based doses and fixed doses of 
monoclonal antibodies have been evaluated, and the 2 approaches performed similarly, with 
body size–based doses not always offering an advantage in reducing variability of exposure 
(Bai et al 2012, Wang et al 2009). 
The proposed flat dose regimen of 500 mg Q4W is based on modeling of clinical PK data from 
the ongoing first-in-human monotherapy study (NCT03059823) and benchmarking to 
pembrolizumab.  This dose-escalation study of INCMGA00012 evaluated 37 subjects at the 
following doses:  1 mg/kg Q2W, 3 mg/kg Q2W, 3 mg/kg Q4W, 10 mg/kg Q2W, and 10 mg/kg 
Q4W.  While supra dose proportionality was observed for AUC and Cmax for the first dose 
escalation from 1 mg/kg to 3 mg/kg, linear PK was shown from 3 mg/kg to 10 mg/kg.  No 
dose-limiting toxicity was observed at any dose level, and an MTD was not reached. 
A population PK analysis was performed on these subjects to characterize the effect of body 
weight on the PK of INCMGA00012.  The plasma concentrations of INCMGA00012 can be 
adequately described by a 2-compartment model with first-order elimination.  Higher clearance 
of INCMGA00012 was estimated for 1 mg/kg than the other dose groups.  Body weight 
dependence of clearance was characterized by a power relationship with an exponent of 0.911. 
A simulation was conducted to investigate the use of body weight–based dosing and flat dosing 
for INCMGA00012, with the aim of targeting a steady-state trough concentration of ≈ 21 μg/mL, 
the median trough concentration for pembrolizumab (Freshwater, 2017).  The median 
INCMGA00012 exposure and distribution around the median at 500 mg Q4W were similar to 
7 mg/kg Q4W in the simulated population, which justified clinical exploration in an expansion 
cohort of the study.  The median steady-state concentration at 500 mg Q4W was 24.8 μg/mL, 
and 58% of subjects had trough concentrations greater than target concentration.  
Pharmacokinetic data were obtained from 15 subjects who received INCMGA00012 500 mg 
Q4W in the Cohort Expansion Phase of Study INCMGA 0012-101.  The observed AUC∞ for 
500 mg Q4W was close to the steady-state AUCt based on the population PK analysis of 
weight-based dosing, as was the estimated clearance.  The estimated t½ (333 hours) was slightly 
shorter than that of the previous estimate of 409 hours.  The mean trough plasma concentration 
on Cycle 2 was 17.1 μg/mL and the mean projected plasma Cmin,ss was 23.1 μg/mL (which meets 
or slightly exceeds the targeted concentration based on pembrolizumab data) with a mean 
accumulation index of 1.50.  Overall, the 500-mg Q4W dose had very similar PK properties to 
3 mg/kg dosing, and has ≈ 77% probability for steady-state trough plasma concentration 
≥ 10 μg/mL, which is associated with maximum target engagement and greatest probability of 
efficacy.  Based on these observations, 500 mg Q4W was chosen as the dosing regimen for 
further development in combination with INCB054828. 




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3. 
SUBJECT ELIGIBILITY 
Deviations from eligibility criteria are not allowed because they can potentially jeopardize the 
scientific integrity of the study, regulatory acceptability, and/or subject safety.  Therefore, 
adherence to the criteria as specified in the Protocol is essential. 
3.1. 
Subject Inclusion Criteria 
The following criteria are required for inclusion in the study: 
1. Male or female subjects, age 18 years or older on day of signing consent. 
2. Willingness to provide written informed consent for the study. 
3. Part 1:  Any advanced solid tumor malignancy. 
Part 1:  Subset of subjects with moderate renal impairment (eGFR:  ≥ 30 to 
< 60 mL/min/m2) and severe renal impairment (eGFR:  < 30 mL/min/m2). 
Part 2:  Subjects with measurable disease with documented FGF/FGFR alterations, 
including multiple myeloma and MPNs.  For subjects enrolling in Part 2 with head and 
neck, vulvar, or anal cancer, must have evidence of positive HPV status.  For BID dosing 
in Part 2, subjects must have a documented FGFR3 mutation or fusion-positive with 
advanced/metastatic bladder cancer. 
Part 3: 
1) Dose finding:  subjects with solid tumor malignancies that have measurable 
disease for which treatment with gemcitabine + cisplatin, docetaxel, trastuzumab, 
and PD-1-directed therapies is relevant. 
2) Dose expansion:  subjects with solid tumor malignancies that have measurable 
disease and are also harboring FGF/FGFR alterations for which treatment with 
gemcitabine + cisplatin, docetaxel, trastuzumab, and PD-1-directed therapies is 
relevant. 
4. Has progressed after prior therapy and either there is no further effective standard 
anticancer therapy available (including subject refuses or is intolerant) or the prescribed 
combination therapy for subjects enrolling in Part 3 is considered a relevant therapy for 
their diagnosis. 
5. Life expectancy > 12 weeks. 
6. ECOG performance status: 
Part 1:  0 or 1. 
Parts 2 and 3:  0, 1, or 2. 


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7. Archival tumor specimen (tumor block or 25 unstained slides, minimum number of slides 
is approximately 15) or willingness to undergo a pretreatment tumor biopsy to provide a 
tumor block or 25 unstained slides (minimum number of slides is approximately 15).  
Archival tumor biopsies are acceptable at baseline and should be no more than 2 years 
old (preferably less than 1 year old and collected since the completion of the last 
treatment); subjects with samples older than 2 years old and/or with sequencing report 
from Foundation Medicine require approval from the sponsor medical monitor for 
exemption from the need for tumor biopsy or tumor sample requirement. 
NOTE:  For subjects in Part 1, fresh tumor biopsies for the purpose of determining study 
eligibility should be limited to tumors where tissue can be safely accessed.  The medical 
monitor should be contacted before the subject is enrolled. 
8. Women of childbearing potential (defined as women who have not undergone surgical 
sterilization with a hysterectomy and/or bilateral oophorectomy and are not 
postmenopausal or sterilized from chemo/radiotherapy, defined as ≥ 12 months of 
amenorrhea) must have a negative serum pregnancy test at screening and prior to the first 
dose on Cycle 1 Day 1.  All women and men of childbearing potential must agree to take 
appropriate precautions to avoid pregnancy or fathering children (with at least 99% 
certainty) from screening through the safety follow-up visit (30-35 days after last dose).  
Subjects enrolled in Part 3 combination with INCMGA00012 should avoid pregnancy or 
fathering a child starting at screening through 6 months after the last dose of 
INCMGA00012.  Permitted methods that are at least 99% effective in preventing 
pregnancy (Appendix A) should be communicated to the subject and their understanding 
confirmed. 
3.2. 
Subject Exclusion Criteria 
If met, any of the following criteria will lead to subject exclusion from the study: 
1. Treatment with other investigational study drug for any indication for any reason, or 
receipt of anticancer medications within 28 days before first dose of study drug (6 weeks 
for mitomycin-C or nitrosoureas, 7 days for tyrosine kinase inhibitors), but may be 
eligible with approval from the sponsor's medical monitor. 
a. Subjects must have recovered (≤ Grade 1 or pretherapy baseline) from AEs due to 
previously administered therapies. 
2. Prior receipt of a selective FGFR inhibitor within the last 6 months. 
3. Inadequate laboratory parameters as indicated below.  All screening laboratory tests 
should be performed within 14 days of treatment initiation. 
Part 1 Dose Escalation: 
a. Hemoglobin < 10.0 g/dL (transfusions are permitted with approximately 2 weeks of 
washout required before enrollment). 
b. Platelet count < 100 × 109/L 
c. Absolute neutrophil count < 1.5 × 109/L 
d. Total bilirubin > upper limit of normal (ULN) unless associated with subject's 
primary cancer and/or metastases and with medical monitor approval 


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e. AST or ALT > ULN unless associated with subject's primary cancer and/or 
metastases and with medical monitor approval 
f. ALP > ULN unless associated with subject's primary cancer and/or metastases and 
with medical monitor approval 
g. Creatinine clearance ≤ 60 mL/min (< 30 mL/min for urothelial carcinoma) based on 
the site's standard formula, except for a subset of subjects with moderate renal 
impairment (eGFR:  ≥ 30 to < 60 mL/min/m2) and severe renal impairment 
(eGFR:  < 30 mL/min/m2) based on the MDRD formula who will be allowed to enter 
the study 
h. Serum calcium outside of the institutional normal range, or serum albumin-corrected 
calcium outside of the institutional normal range if serum albumin is outside of the 
institutional normal range 
i. Serum phosphorus outside of the ULN of the institutional normal range 
j. Parathyroid hormone > 1.5 × ULN of the institutional normal range 
Part 2 Expansion: 
a. Hemoglobin ≤ 9.0 g/dL(transfusions are permitted with approximately 2 weeks of 
washout required before enrollment). 
b. Platelet count ≤ 75 × 109/L 
c. Absolute neutrophil count ≤ 1.0 × 109/L 
d. Total bilirubin ≥ 1.5 × institutional ULN unless associated with subject's primary 
cancer and/or metastases and with medical monitor approval 
e. AST or ALT ≥ 3 × ULN unless associated with subject's primary cancer and/or 
metastases and with medical monitor approval 
f. ALP ≥ 2.5 × ULN unless associated with subject's primary cancer and/or metastases 
and with medical monitor approval 
g. Creatinine clearance ≤ 40 mL/minute (< 30 mL/min for multiple myeloma or 
urothelial carcinoma) based on the site's standard formula 
h. Serum calcium outside of the institutional normal range, or serum albumin-corrected 
calcium outside of the institutional normal range if serum albumin is outside of the 
institutional normal range 
i. Serum phosphorus outside of the ULN of the institutional normal range 
j. Parathyroid hormone > 1.5 × ULN of the institutional normal range 
Note:  Hematological parameters do not apply to subjects with MPN. 
Part 3 Combination: 
k. Hemoglobin ≤ 9.0 g/dL (transfusions are permitted with approximately 2 weeks of 
washout required before enrollment). 
l. Platelet count ≤ 75 × 109/L 
m. Absolute neutrophil count ≤ 1.5 × 109/L 
n. Total bilirubin ≥ 1.5 × institutional ULN unless associated with subject's primary 
cancer and/or metastases and with medical monitor approval 
o. AST or ALT ≥ 3 × ULN unless associated with subject's primary cancer and/or 
metastases and with medical monitor approval 
p. ALP ≥ 2.5 × ULN unless associated with subject's primary cancer and/or metastases 
and with medical monitor approval 


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q. Creatinine clearance ≤ 40 mL/minute (< 30 mL/min for urothelial carcinoma) based 
on the site's standard formula 
r. International normalized ratio or prothrombin time > 1.5 × ULN, unless on warfarin 
s. Activated partial thromboplastin time > 1.5 × ULN 
t. Serum calcium outside of the institutional normal range, or  serum albumin-corrected 
calcium outside of the institutional normal range when serum albumin is outside of 
the institutional normal range 
u. Serum phosphorus outside of the ULN of the institutional normal range 
v. Parathyroid hormone > 1.5 × ULN of the institutional normal range 
4. History of calcium and phosphate homeostasis disorder or systemic mineral imbalance 
with ectopic calcification of soft tissues (exception:  commonly observed calcifications in 
soft tissues, such as the skin, kidney, tendons, or vessels due to injury, disease, and aging, 
in the absence of systemic mineral imbalance). 
5. History of hypersensitivity to any of the study drugs. 
6. History and/or current evidence of ectopic mineralization/calcification, except 
intratumoral calcification secondary to tumor necrosis or previous treatment 
(eg, transarterial chemoembolization, chemotherapy) and calcified lymph nodes and 
asymptomatic arterial or cartilage/tendon calcification.  Combined with #4 in Protocol 
Amendment 7. 
7. Current evidence of clinically significant corneal disorder/keratopathy (including but not 
limited to bullous/band keratopathy, corneal abrasion, inflammation/ulceration, 
keratoconjunctivitis), or retinal disorder (including but not limited to macular/retinal 
degeneration, diabetic retinopathy, retinal detachment), confirmed by ophthalmologic 
examination. 
8. History or presence of an abnormal electrocardiogram (ECG) that in the investigator's 
opinion is clinically meaningful.  A screening QTc interval > 470 msec, as corrected by 
Fridericia, is excluded.  For subjects with an intraventricular conduction delay 
(QRS interval 120 msec), the JTc interval may be used in place of the QTc with sponsor 
approval.  The JTc must be ≤ 340 milliseconds if JTc is used in place of the QTc. 
9. Prior radiotherapy within 2 weeks of study treatment.  Subjects must have recovered from 
all radiation-related toxicities, not require corticosteroids, and not have had radiation 
pneumonitis.  Evidence of fibrosis within a radiation field from prior radiotherapy is 
permitted with medical monitor approval.  A 1-week washout period is permitted for 
palliative radiation to non–central nervous system (CNS) disease with medical monitor 
approval.  
a. Subjects enrolled into Part 3 (pembrolizumab or INCMGA00012 combination), 
should have a minimum of a 6-month washout period after thoracic radiotherapy if 
> 30 Gy was received. 
10. Use of any potent CYP3A4 inhibitor or inducer or moderate CYP3A4 inducer within 
14 days or 5 half-lives (whichever is longer) of the first dose of study drug 
(see Section 5.12). 
11. History of human immunodeficiency virus infection. 


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12. Untreated brain or CNS metastases or brain/CNS metastases that have progressed 
(eg, evidence of new or enlarging brain metastasis or new neurological symptoms 
attributable to brain/CNS metastases).  Subjects with treated brain metastases are eligible 
if there is no evidence of progression for at least 4 weeks after CNS-directed treatment, as 
ascertained by clinical examination and brain imaging (MRI or CT scan) during the 
screening period, and they are on a stable or decreasing dose of corticosteroids for at least 
1 week. 
13. Active chronic or current infectious disease requiring systemic antibiotic, antifungal, or 
antiviral treatment within 2 weeks prior to enrollment (subjects with asymptomatic 
chronic infections on prophylactic treatment are allowed). 
14. History of clinically significant or uncontrolled cardiac disease including unstable angina, 
acute myocardial infarction within 6 months from Day 1 of study treatment 
administration, New York Heart Association Class III or IV congestive heart failure, or 
uncontrolled arrhythmia requiring therapy (subjects with pacemaker or with atrial 
fibrillation and well-controlled heart rate are allowed). 
15. History of allergic reactions to INCB054828, any of the excipients of INCB054828 or 
similar compounds, gemcitabine, cisplatin, docetaxel, pembrolizumab, trastuzumab, or 
INCMGA00012.  History of infusion allergic reactions to antibodies (eg, pembrolizumab, 
trastuzumab, or INCMGA00012) that are able to be managed with standard measures 
(eg, H2 blockers and/or steroids) are allowed. 
16. Unable or unwilling to swallow INCB054828 or significant GI disorder(s) that could 
interfere with the absorption, metabolism, or excretion. 
17. Inadequate recovery from toxicity and/or complications from a major surgery prior to 
starting therapy. 
18. Known additional malignancy that is progressing or requires active treatment.  
Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, 
superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the 
cervix, or other noninvasive or indolent malignancy that has undergone potentially 
curative therapy. 
19. Pregnant or nursing women or subjects expecting to conceive or father children within 
the projected duration of the study, starting with the screening visit through completion of 
safety follow-up visit (30-35 days after last dose).  Subjects enrolled in Part 3 
combination with INCMGA00012 should avoid pregnancy or fathering a child starting at 
screening through 6 months after the last dose of INCMGA00012. 
20. Any condition that would in the investigator's judgment interfere with full participation in 
the study, including administration of study medication and attending required study 
visits; pose a significant risk to the subject; or interfere with interpretation of study data. 
21. Subjects who require hemodialysis.  Removed in Protocol Amendment 7. 
22. Subjects being considered for treatment in the trastuzumab combination group (Part 3) 
with LVEF of < 50% on echocardiogram or multigated acquisition (MUGA) scan. 


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23. Evidence of active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (defined 
as subjects with elevated transaminases or cirrhosis.  Subjects with chronic HBV/HCV 
infection with no cirrhosis and no elevated transaminases are allowed). 
24. Any prior PD-1– or PD-L1–directed treatment for which permanent discontinuation of 
therapy is recommended, per USPI. 
25. Active autoimmune disease requiring systemic immunosuppression in excess of 
physiologic maintenance doses of corticosteroids. 
26. Subjects receiving pembrolizumab or INCMGA00012 and have received a live vaccine 
within 28 days of planned start of study treatment. 
Note:  Examples of live vaccines include but are not limited to the following:  
measles, mumps, rubella, chicken pox/zoster, yellow fever, rabies, Bacillus 
Calmette-Guérin, and typhoid vaccine.  Seasonal influenza vaccines for injection are 
generally killed virus vaccines and are allowed; however, intranasal influenza 
vaccines (eg, FluMist®) are live-attenuated vaccines and are not allowed. 
27. Evidence of interstitial lung disease or active, noninfectious pneumonitis. 
4. 
INVESTIGATIONAL PLAN 
4.1. 
Overall Study Design 
This is an open-label, dose-escalation study of the FGFR inhibitor INCB054828 in subjects with 
advanced malignancies.  Subjects will receive QD doses of INCB054828 on a 2-weeks-on 
therapy and 1-week-off therapy schedule; a continuous administration regimen will also be 
explored, which will include BID administration as well.  The study will be conducted in 3 parts 
(Figure 3).  Part 1 (monotherapy dose escalation) will determine the MTD of INCB054828 
and/or doses/regimen that produce substantial evidence of pharmacologic target inhibition 
(increased serum phosphate), and approximately 20 subjects will participate in the effect of renal 
impairment on safety and PK (approximately 10 moderate and 10 severe). 
Part 2 (monotherapy dose expansion) will evaluate the dose(s) selected in Part 1 as a 
monotherapy in specific indications where activity of FGFR is particularly relevant and that have 
amplification, mutation, or translocation of FGFR 1, 2, or 3, or alteration of FGF 1 through 23.  
Additionally, as part of the dose expansion, all subjects enrolling in the tumor-specific cohorts 
(n = 20 total, n = 5 per cohort) will have mandatory biopsies, and approximately 8 subjects will 
participate in a food-effect study.  Approximately 10 subjects will be enrolled into a very specific 
cohort to further evaluate the BID dosing regimen.  Subjects will be required to have FGFR3 
mutated or fusion-positive advanced/metastatic bladder cancer. 
Part 3 will begin with dose-finding to determine RP2Ds of INCB054828 in combination with 
gemcitabine + cisplatin, docetaxel, pembrolizumab, trastuzumab, or INCMGA00012 in subjects 
with tumors for which gemcitabine + cisplatin, docetaxel, pembrolizumab, trastuzumab, or 
INCMGA00012 treatment is relevant.  Dose-expansion will further evaluate the RP2Ds selected 
in these populations harboring FGF/FGFR alterations. 


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Treatment may continue as long as subjects are receiving benefit and have not met any criteria 
for study withdrawal.  Subjects who discontinue study drug will continue to be followed for 
subsequent anticancer treatments and survival. 
4.1.1. 
Part 1 Dose Escalation 
The study will begin with an open-label dose escalation with an accelerated titration design 
based on observing each dose level for a period of 21 days before enrolling the next cohort and 
administering the next dose level.  In Part 1, subjects who receive at least 11 out of 14 doses of 
study drug at the level assigned to that cohort or have a DLT will be considered evaluable for 
determining tolerability of the dose.  Subjects enrolling but not meeting these criteria may be 
replaced in order to fill the cohort.  Up to approximately 60 subjects will be enrolled. 
The initial cohorts will consist of at least 1 subject each, and the doses may be increased up to 
2-fold in successive cohorts until a Grade 2 or greater toxicity (excepting toxicities with a clear 
alternative explanation [eg, due to disease progression] or transient [≤ 72 hours] abnormal 
laboratory values without clinically significant signs or symptoms) or HP (serum phosphate 
> 5.5 mg/dL) is observed, at which time that cohort will be expanded to at least 3 subjects.  From 
the point where a single-subject cohort is first expanded to 3 subjects, subsequent cohorts will 
enroll a minimum of 3 subjects, and increases to study drug dose will be limited to no more than 
50% in successive cohorts, utilizing QD doses.  If no DLTs are observed in the initial 3 subjects, 
then the next cohort will begin enrollment.  If 1 DLT is observed in the first 3 subjects, then 
3 additional subjects will be enrolled in the cohort.  If a DLT occurs in 2 or more subjects in a 
cohort of 3 or 6, then the MTD will be deemed to have been exceeded, and the next lower dose 
level will be deemed to be the MTD.  Thus, the MTD will be defined as 1 dose level below that 
at which one-third or more of subjects in a particular cohort report a DLT.  If a DLT is observed 
at the initial dose of 1 mg QD, then a dose decrease to 0.5 mg may be considered.  
An intermediate dose level may also be explored.  See Section 5.6 for DLT definitions.  If 
toxicities specifically relevant to a type of malignancy are observed, then a separate dose 
escalation or dose decrease group will be initiated for subjects with this malignancy. 
The effect of renal impairment on the safety and PK of INCB054828 will be conducted in a 
subset of subjects (approximately 10 with moderate renal impairment and 10 with severe) 
enrolled in Part 1 at 13.5 mg continuous administration. 
Continuous study drug administration will be tested in separate dose-escalation cohorts.  The 
starting dose of continuous administration will be lower than the MTD identified in the 
2-weeks-on therapy/1-week-off therapy schedule.  Subjects who receive at least 18 of 21 doses 
of study drug at the level assigned to that cohort or who have a DLT will be considered evaluable 
for determining tolerability of the dose.  Subjects enrolling but not meeting these criteria may be 
replaced in order to fill the cohort. 
Twice daily administration will be tested in a dose-escalation cohort as monotherapy only.  The 
BID starting dose will be 7.5 mg on a continuous dosing schedule (no planned dose hold).  
Subjects who receive at least 35 of a possible 42 doses of study drug at the level assigned to that 
cohort or have a DLT will be considered evaluable for determining tolerability of the dose.  
Subjects enrolling but not meeting these criteria may be replaced in order to fill the cohort.  A 
total of approximately 21 subjects will be enrolled in this cohort for Part 1. 


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4.1.1.1. 
Pharmacodynamic Target 
Dose escalation will proceed in the absence of an MTD to a PAD.  The PAD is defined as the 
point where approximately 67% of subjects (2 out of 3) attain HP; in a cohort of 3 subjects, if 
2 out of 3 have HP, then the cohort will be expanded to 6 (while dose escalation continues as 
described above).  Once the PAD is achieved, a new cohort will be enrolled where subjects will 
be treated with diet modification (decreased phosphate intake) and phosphate binders, and dose 
escalation will continue to determine the dose at which at least one-third of subjects attain HP 
and an MTD is identified.  Alternative PAD can be defined by molecular endpoint such as the 
inhibition of FGFR and/or at least a 1.5-fold increase of serum phosphate. 
4.1.1.2. 
Recommended Part 2 Dose 
Based on safety and tolerability data and the PD measure of serum phosphate levels, the RP2D(s) 
(dose and/or regimen) will be defined and will be the lower of the MTD or the PAD with or 
without prophylactic concomitant phosphate binders; different RP2Ds may be determined for 
interval administration and continuous administration.  Multiple RP2Ds may be used moving 
into Part 2 and Part 3. 
4.1.1.3. 
Lower Dose Level Expansion 
Up to 3 additional subjects may be enrolled at any dose level for the interval and continuous 
administration monotherapy regimens, as well as the combination regimens, that is deemed to be 
pharmacodynamically active (hyperphosphatemia observed in two-thirds of treated subjects) if 
that dose level is below the MTD.  Subjects enrolled in the lower dose level cohort must have 
FGF/FGFR alteration and are required to have a baseline biopsy and at least 1 on-treatment 
biopsy (recommended at Cycle 2 Day 14 but allowed to be performed at any cycle; must be 
performed on a study drug administration day, preferably between Day 8 and Day 14).  
Additionally, an EOT/at time of progression biopsy is requested but not required.  
 
 
4.1.2. 
Part 2 Dose Expansion 
When the recommended doses and/or regimen for Part 2 investigation have been determined, 
enrollment will proceed for Part 2.  It is possible that a different dose and/or regimen will be 
chosen for subjects with different types of malignancies. 
Approximately 120 subjects with advanced malignancies that have been evaluated and 
confirmed to harbor genetic alterations in FGF or FGFR genes will be treated in the 
dose-expansion cohort to further determine safety, tolerability, efficacy, PK, food effect, and PD.  
A subject's FGFR alteration can be based on local laboratory results and retrospectively 
confirmed by a central laboratory. 
Approximately 70 subjects will be enrolled in Part 2, regardless of tumor type but harboring a 
FGF/FGFR alteration.  Approximately 20 subjects will be enrolled into 1 of 4 potential tumor 
type-cohorts:  cholangiocarcinoma (FGFR2 translocated only) (n = 5), bladder (n = 5), lung 
(n = 5), and HPV positive with FGFR-alteration tumors, including but not limited to head and 
neck (HNC), vulvar, and anal tumors (n = 5).  A specific cohort of approximately 10 subjects 
with FGFR3 mutated or fusion-positive advanced/metastatic bladder cancer will be included in 
Part 2 as well.  All subjects in each tumor-type cohort will be required to undergo a baseline 


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biopsy and at least 1 on-treatment biopsy (recommended at Cycle 2 Day 14 but allowed to be 
performed at any cycle; must be performed on a study drug administration day, preferably 
between Day 8 and Day 14).  Additionally, an EOT/at time of progression biopsy is requested 
but not required.  NOTE:  Subjects who consent to the mandatory biopsy and withdraw consent 
after starting study treatment will be considered Protocol deviations. 
A food-effect study will be conducted in approximately 8 subjects who will already be enrolled 
in Part 2 to determine if INCB054828 PK is affected by food (see Section 7.7.2). 
Treatment will be initiated at an RP2D(s).  Subjects who attain HP should follow guidelines for 
HP management as per Section 0.  Subjects that do not attain HP or at least a 1.5-fold increase 
from baseline of serum phosphate after the first cycle of treatment should have their dose 
increased each cycle to the previously study assessed doses or 25% dose increments (whichever 
is a smaller increment) until HP or the maximum safely tested dose is reached. 
4.1.3 
Part 3 Combination Dose Finding and Expansion 
Part 3 will comprise treatment groups evaluating INCB054828 administered in combination with 
standard therapies for select solid tumors.  Part 3 will include dose finding and dose expansion.  
Dose finding will be a 3 + 3 enrollment design that will evaluate different doses of INCB054828 
in combination with agents utilized in the treatment of solid tumors.  The dose expansion is to 
further evaluate the safety and preliminary efficacy of the combination in select tumor types at 
the selected INCB054828 dose. 
Approximately 60 subjects will be enrolled in the dose-finding group.  The starting dose for 
Part 3 will be the RP2D(s). 
Initially, at least 3 subjects will be enrolled in each treatment group for dose finding.  The 
treatment groups include INCB054828 in combination with gemcitabine/cisplatin, docetaxel, 
pembrolizumab, trastuzumab, or INCMGA00012 at the doses, schedules, and routes described 
below.  If in each group no DLTs are observed, then enrollment of the corresponding expansion 
will begin.  If 1 DLT is observed, then at least 6 subjects will be enrolled in the dose-finding 
treatment group.  If DLTs are observed in 2 or more subjects in a 3- or 6-subject group, then the 
dose of INCB054828 will be reduced by 25% to 50%.  Dose assessment and dose decrease may 
be repeated once more.  The combination MTD will be the highest dose of INCB054828 in each 
combination at which ≤ 0/3 or 1/6 subjects experience DLTs.  The combination RP2D will be a 
dose less than or equal to the MTD/PAD dependent on emergent pharmacodynamics, PK, and 
safety data and may be specific to the different combination therapies. 
Up to 3 additional subjects with known FGF/FGFR alterations may be enrolled at any Part 3 
dose level if that dose level is below the MTD.  In addition, the subjects enrolled in the lower 
dose level cohort per treatment combination are required to have a baseline biopsy and at least 
1 on-treatment biopsy (recommended at Cycle 2 Day 14 but allowed to be performed at any 
cycle; must be performed on a study drug administration day, preferably between Day 8 and 
Day 14).  Additionally, an EOT/at time of progression biopsy is requested but not required.  
 
 
In the Part 3 combination expansion treatment groups, approximately 75 subjects will be 
enrolled, including approximately 6 subjects per combination (if appropriate) for mandatory 
baseline and on-treatment biopsies. 






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5. 
TREATMENT OF SUBJECTS 
5.1. 
Treatment Groups and Administration of Study Drug 
5.1.1. 
Treatment Regimen for INCB054828  
Subjects will self-administer study drug using an oral QD regimen in a 2-weeks-on therapy and 
1-week-off therapy schedule; a continuous administration regimen will also be explored.  Study 
drug can be taken with or without food.  On days when PK samples will be collected, subjects 
should fast for 8 hours before taking study drug in the clinic and fast for 1 additional hour after 
taking study drug.  If a dose is missed by more than 4 hours, the subject should skip the dose and 
take the next scheduled dose at the usual time.  Any missed doses reported by the subject should 
be recorded in the subject's source documents. 
One cycle will be defined as 21 continuous days of planned study treatment.  The treatment cycle 
regimen consists of the following: 
• Days 1 through 14:  INCB054828 orally QD (suggested in morning).  Extension of 
INCB054828 treatment into the recovery period is not permitted. 
• Days 15 through 21:  treatment break. 
The continuous dosing regimen will still adhere to the 21-day cycle but instead of a planned dose 
hold from Days 15 to 21, subjects will continue taking study medication with no planned dose 
hold. 
The BID regimen will also adhere to the 21-day cycle, but subjects will take study medication 
2 times per day (AM and PM) and will also follow the continuous dosing regimen (no planned 
dose hold). 
5.1.2. 
Treatment Regimen for Gemcitabine + Cisplatin (Part 3 Only) 
Subjects will receive gemcitabine intravenously starting at 1000 mg/m2 (30 minutes) on Days 1 
and 8 of each 21-day cycle.  Cisplatin will be administered intravenously starting at 70 mg/m2 
(1-4 hours) once every 3 weeks on Day 1 of each 21-day cycle.  Both gemcitabine and cisplatin 
doses can be adjusted for toxicity management per commercial labeling.  The investigator may 
choose to interrupt, modify, or discontinue chemotherapy with medical monitor approval.  
INCB054828 administration may continue during the toxicity break of gemcitabine/cisplatin. 
5.1.3. 
Treatment Regimen for Docetaxel (Part 3 Only) 
Subjects will receive docetaxel intravenously starting at 75 mg/m2 (1 hour) once every 3 weeks 
on Day 1 of each cycle.  The dose can be adjusted for toxicity management per commercial 
labeling.  The investigator may choose to interrupt, modify, or discontinue chemotherapy with 
medical monitor approval.  INCB054828 administration may continue during the toxicity break 
of docetaxel. 


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5.1.4. 
Treatment Regimen for Pembrolizumab (Part 3 Only) 
Subjects will receive pembrolizumab intravenously at 200 mg (30 minutes) once every 3 weeks 
on Day 1 of each cycle.  The dose can be adjusted for toxicity management per commercial 
labeling.  The investigator may choose to interrupt, modify, or discontinue pembrolizumab with 
medical monitor approval.  INCB054828 administration may continue during the toxicity break 
of pembrolizumab. 
5.1.5. 
Treatment Regimen for Trastuzumab (Part 3 Only) 
Trastuzumab will be administered as an open-label, commercial product at an initial dose of 
8 mg/kg over a 90-minute IV infusion, followed by 6 mg/kg over a 30- to 90-minute IV infusion 
once every 3 weeks.  The dose can be adjusted for toxicity management, per commercial 
labeling.  The investigator may choose to interrupt, modify, or discontinue trastuzumab with 
medical monitor approval.  INCB054828 administration may continue during the toxicity break 
of trastuzumab. 
5.1.6. 
Treatment Regimen for INCMGA00012 (Part 3 Only) 
INCMGA00012 will be administered as an open-label product at an initial dose of 500 mg over a 
60-minute IV infusion.  It will be administered once Q4W on a 28-day cycle.  Table 5 shows the 
different dose level options for each cohort. 
Table 5: 
Dose Levels for INCMGA00012 in Combination With INCB054828 
Cohort 
INCB054828 
INCMGA00012 
1 
9 mg QD, continuous 
500 mg Q4W 
2 
13.5 mg QD, continuous 
500 mg Q4W 
5.2. 
Treatment Compliance 
Subjects should be counseled by the investigator to maintain strict adherence to the study 
regimen as prescribed and to keep a record of any missed doses.  The subject will be instructed 
to bring all unopened, empty, and opened/partially used bottles of study drug to each study visit, 
at which time compliance will be assessed. 
5.3. 
Randomization and Blinding 
Not applicable. 
5.4. 
Duration of Treatment and Subject Participation 
Subjects will be treated in continuous cycles indefinitely; this may include temporary 
interruptions.  If INCB054828 is permanently discontinued, the subject will be withdrawn from 
the study.  All subjects will attend study visits weekly during the first 6 cycles.  Treatment 
duration will vary significantly between subjects, but is expected to average approximately 
6 months. 






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• In the opinion of the investigator, the subject does not have any concurrent condition 
or circumstance that would complicate the dose escalation, PK sampling, or pose 
increased risk to the subject. 
• The intrasubject dose escalation has been approved by the sponsor. 
Any subject treated at 13.5 mg should be titrated up to 18 mg QD using their current dose 
regimen with approval from the medical monitor if they meet the following criteria: 
• have been on study drug for at least 1 cycle, 
• have been compliant with taking study drug, 
• have no ongoing Grade 2 or higher treatment-related AE, 
• have not achieved hyperphosphatemia defined as a serum phosphate level of 
> 5.5 mg/dL. 
Subjects who are titrated up to 18 mg QD will begin the next cycle at the new dose level and 
must agree to all Cycle 1 assessments (PK and safety assessments [hematology and blood 
chemistry]).  Up-titration may occur no earlier than Cycle 2 Day 1, so that subjects are observed 
for phosphate level and AEs for at least 1 cycle. 
5.8.2. 
Criteria and Procedures for Interruption of INCB054828 
Treatment with INCB054828 may be delayed up to 2 weeks (14 days), including the planned 
dose hold to allow for resolution of toxicity.  It is recommended that subjects with suspected or 
documented serous retinal detachment be discussed with the Incyte medical monitor before 
adjusting the study drug regimen. 
Subjects may resume treatment if no medical condition or other circumstance exists that, in the 
opinion of the investigator, would make the subject unsuitable for further participation in the 
study.  The treating investigator should contact the sponsor's medical monitor to discuss the case 
of any subject whose treatment has been delayed for more than 14 days before restarting 
treatment with INCB054828. 
Day 1 of each study cycle will correspond with the first day of INCB054828 administration in 
that cycle; thus, study cycles may become out of sync with the originally planned schedule if 
treatment is delayed for safety.  In this event, tumor assessments will remain on the original 
schedule.  All other assessments will shift to coincide with the revised treatment (cycle) 
schedule.  The treating investigator should contact the sponsor's medical monitor to discuss any 
case in which a subject's study drug was interrupted to determine the best place to restart the 
subject's study drug. 
For subjects who present with possible or confirmed serous retinal detachment/retinal pigmented 
epithelium detachment (SRD/RPED) based on optic coherence tomography, the guidelines in 
Table 7 should be followed.  It is recommended to discuss the findings with the Incyte medical 
monitor before making changes to the subject's treatment. 
Per CTCAE v4.03, there is a grading for retinal detachment; however, this refers to 
rhegmatogenous retinal detachment (when a hole occurs in the retina) or exudative detachment 
(fluid accumulation due to inflammatory diseases).  There is no exact CTCAE grading term for 
SRD/RPED secondary to FGFR inhibition (there is no hole in the macula, just fluid 






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Table 8: 
Recommended Approach for Hyperphosphatemia Management 
Serum Phosphate 
Level 
Supportive Care 
Guidance for 
Interruption/Discontinuation  
of INCB054828 
Guidance for 
Restarting 
INCB054828 
> 5.5 mg/dL and 
≤ 7 mg/dL 
Initiate a low-phosphate diet  
No action. 
Not applicable. 
> 7 mg/dL and 
≤ 10 mg/dL  
First occurrence:  Initiate 
low-phosphate diet and 
phosphate-binding therapy until 
return to ≤ 7 mg/dL. 
Second/continued occurrence:  
initiate/continue low-phosphate 
diet and start/adjust phosphate 
binding therapy until return to 
≤ 7 mg/dL. 
Monitor serum phosphate at 
least twice a week. 
If serum phosphate level 
continues to be > 7 mg/dL and 
≤ 10 mg/dL with concomitant 
phosphate-binding therapy for 
2 weeks, interrupt study drug for 
up to 2 weeks (including the 
planned dose interruptions per 
treatment cycle for subjects 
receiving the interval regimen). 
Restart at the same dose 
when serum phosphate is 
≤ 7 mg/dL. 
If, after restarting, serum 
phosphate level recurs at 
> 7 mg/dL, study drug 
dose should be reduced. 
> 10 mg/dL 
First occurrence:  Initiate a 
low-phosphate diet, 
phosphate-binding therapy, and 
phosphaturic agent until return 
to normal range. 
Second/continued occurrence:  
start/continue low-phosphate 
diet and start/adjust phosphate-
binding therapy and 
phosphaturic agent until return 
to ≤ 7 mg/dL. 
Continue to monitor serum 
phosphate at least twice a week. 
If serum phosphate level 
continues to be > 10 mg/dL for 1 
week after supportive measures, 
interrupt study drug for up to 2 
weeks (including the planned 
dose interruptions per treatment 
cycle for subjects receiving the 
interval regimen).   
If there is recurrence of serum 
phosphate level in this range 
after 2 dose reductions, 
permanently discontinue 
study drug. 
Restart study drug at 
reduced dose with 
phosphate binders when 
serum phosphate is 
≤ 7 mg/dL. 
If, after restarting, serum 
phosphate level recurs at 
> 10 mg/dL, study drug 
dose should be reduced. 
5.8.4. 
Criteria for Permanent Discontinuation of INCB054828 
The occurrence of unacceptable AEs will require that the study drug be permanently 
discontinued.  Unacceptable AEs are defined as: 
• Occurrence of an AE, which in the judgment of the investigator or the sponsor's 
medical monitor, compromises the subject's ability to continue study-specific 
procedures or is considered to not be in the subject's best interest. 
• AEs requiring more than 2 dose reductions (unless dose was increased) below the 
starting dose of INCB054828 or PAD of INCB054828 if the PAD has been 
established. 
• Persistent AEs (including hyperphosphatemia) requiring a delay of therapy for more 
than 2 weeks (14 days), including the planned dose hold, unless a greater delay has 
been approved by the medical monitor. 
• Serum phosphate levels in line with Table 6 and Table 8. 
• Concurrent elevation of ALT > 3 × ULN and total bilirubin > 2 × ULN in subjects 
who do not have evidence of biliary obstruction or other causes that can reasonably 
explain the concurrent elevations. 
If study drug is permanently discontinued, see Sections 6.3 and 6.4 for follow-up assessments. 


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5.8.5. 
Dose Modifications and Management of Adverse Events Associated With 
Gemcitabine + Cisplatin, Docetaxel, Pembrolizumab, or Trastuzumab 
If an AE or safety issue is considered to be associated with gemcitabine, cisplatin, docetaxel, 
pembrolizumab, or trastuzumab, then institutional guidelines for its management should be 
followed, and/or each drug label should be consulted, and if needed, the sponsor's medical 
monitor should be consulted. 
5.8.6. 
Dose Modification and Management of Adverse Events for INCMGA00012 
Pre-treatment criteria that should be met prior to treatment from Cycles 2 and onward include: 
• Hemoglobin ≥ 8 g/dL. 
• ANC ≥ 1.0 × 109/L. 
• Platelet count ≥ 75 × 109/L. 
• ALT/AST/bilirubin ≤ Grade 2. 
• Resolution of all immune-related toxicity to ≤ Grade 1 (with the exception of 
endocrinopathy that is controlled on hormonal replacement). 
• Resolution of all non–immune-related toxicity to Grade ≤ 1 or baseline (with the 
exception of alopecia or non–transfusion-dependent anemia). 
Note:  Transient asymptomatic laboratory elevations ≤ Grade 3 do not require dose 
interruption or reduction if the subject is asymptomatic and the elevation is clinically 
insignificant and has been discussed with the medical monitor (eg, amylase, lipase). 
• Daily dose of corticosteroid ≤ 10 mg prednisone or equivalent. 
Subjects unable to restart study drug treatment ≤ 12 weeks from the start of the treatment delay 
due to toxicity will be permanently discontinued from receiving INCMGA00012.  However, 
INCB054828 may continue if the investigator believes the subject is receiving benefit and 
obtains medical monitor approval to continue monotherapy of INCB054828. 
Treatment breaks of greater than 12 weeks for reasons other than toxicity (eg, for targeted 
radiotherapy) will be considered on a case-by-case basis by the medical monitor. 
INCB054828 can continue during any toxicity break that is considered related to 
INCMGA00012. 
5.8.6.1. 
Management of Suspected Infusion Reactions 
Premedication prophylaxis for infusion reactions is not required for INCMGA00012 but should 
follow institutional preferences.  Guidelines for management of suspected infusion reactions are 
provided in Table 9.  Grade 3 or 4 infusion reactions should be reported within 24 hours to the 
study medical monitor regardless of whether criteria for reporting as an SAE are met. 


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Table 9: 
Guidelines for Management of Suspected Infusion Reactions 
Grade 
Descriptiona 
Treatment 
Subsequent Infusions 
1 
Mild reaction; infusion 
interruption not indicated; 
intervention not indicated. 
Monitor vital signs closely until 
medically stable. 
Additional prophylaxis not 
required. 
2 
Requires infusion interruption but 
responds promptly to 
symptomatic treatment 
(eg, antihistamines, NSAIDS, 
narcotics, IV fluids); prophylactic 
medications indicated for 
≤ 24 hours. 
First occurrence:  Stop infusion 
and initiate appropriate medical 
measures (eg, IV fluids, 
antihistamines NSAIDS, 
acetaminophen/paracetamol, 
narcotics, per institutional 
preferences). 
Monitor vital signs until medically 
stable. 
If symptoms resolve within 1 hour, 
infusion may be resumed at 50% of 
the original infusion rate. 
Subsequent occurrences (after 
recommended prophylaxis):  
Permanently discontinue treatment. 
Premedicate at least 
30 minutes before infusion 
with antihistamines 
(eg, diphenhydramine 
50 mg PO) and 
acetaminophen/paracetamol 
(500-1000 mg PO). 
Additional supportive 
measures may be acceptable 
(per institutional preference) 
but should be discussed with 
medical monitor. 
3 or 4 
Grade 3:  Prolonged (ie, not 
rapidly responsive to symptomatic 
medication and/or brief 
interruption of infusion); 
recurrence of symptoms following 
initial improvement; 
hospitalization indicated for other 
clinical sequelae (eg, renal 
impairment, pulmonary 
infiltrates). 
Grade 4:  Life-threatening; 
pressor or ventilatory support 
indicated. 
Stop infusion and initiate 
appropriate medical therapy 
(eg, IV fluids, antihistamines 
NSAIDS, 
acetaminophen/paracetamol, 
narcotics, oxygen, pressors, 
epinephrine, corticosteroids, per 
institutional preferences). 
Monitor vital signs frequently until 
medically stable.  Hospitalization 
may be indicated. 
Discontinue study drug. 
a Per NCI CTCAE v4.03, appropriate resuscitation equipment should be available at the bedside and a physician readily 
available during the period of study drug administration. 
5.8.6.2. 
Management of Suspected Immune-Related Adverse Events 
Adverse events of a potential immunologic etiology or irAEs may be defined as an AE of 
unknown etiology, associated with drug exposure, and consistent with an immune phenomenon.  
Immune-related AEs may be predicted based on the nature of the compounds, their mechanism 
of action, and reported experience with immunotherapies that have a similar mechanism of 
action.  Special attention should be paid to AEs that may be suggestive of potential irAEs.  An 
irAE can occur shortly after the first dose or several months after the last dose of treatment. 
If an irAE is suspected, efforts should be made to rule out neoplastic, infectious, metabolic, 
toxin, or other etiologic causes before labeling an AE as an irAE.  Algorithms for evaluation of 
selected immune toxicities that have previously been attributed to PD-1 inhibitors 
(Brahmer et al 2018) are provided in the Study Procedures Manual. 


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Recommendations for management of specific immune-mediated AEs known to be associated 
with other PD-1 inhibitors (eg, pembrolizumab, nivolumab) are detailed in the sections below. 
Management guidance for irAEs not detailed elsewhere in the Protocol should follow the 
established guidelines (Brahmer et al 2018). 
5.8.6.3. 
Immune-Mediated Pneumonitis 
Subjects with symptomatic pneumonitis should immediately stop receiving study drug and have 
an evaluation.  The evaluation may include bronchoscopy and pulmonary function tests to rule 
out other causes such as infection.  If the subject is determined to have study drug–associated 
pneumonitis, the suggested treatment plan is detailed in Table 10. 
Table 10: 
Recommended Approach to Handling Pneumonitis 
Study Drug–Associated 
Pneumonitis 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 (asymptomatic) 
No action. 
Intervention not indicated. 
Grade 2 
Withhold study drug. 
Systemic corticosteroids are 
indicated (initial dose of 1-2 mg/kg 
per day of prednisone or 
equivalent).  Taper as appropriate. 
Grades 3 and 4 or recurrent Grade 2 
Permanently discontinue study drug. 
Systemic corticosteroids are 
indicated. 
a Criteria for restarting study drug are in Section 5.8.6. 
5.8.6.4. 
Immune-Mediated Colitis 
Subjects should be carefully monitored for signs and symptoms of colitis (such as diarrhea, 
abdominal pain, mucus, or blood in stool, with or without fever).  In symptomatic subjects, 
infectious etiologies should be ruled out, and endoscopic evaluation should be considered for 
persistent or severe symptoms.  Recommendations for management of enterocolitis are shown in 
Table 11. 
Table 11: 
Recommended Approach for Handling Enterocolitis/Diarrhea 
Study Drug–Associated 
Enterocolitis/Diarrhea 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action. 
All subjects who have diarrhea should be 
advised to drink liberal quantities of clear 
fluids.  If sufficient oral fluid intake is not 
feasible, fluid and electrolytes should be 
substituted via IV infusion.  An 
antidiarrheal can be started. 
Grade 2 
Withhold study drug. 
Systemic corticosteroids are indicated 
(initial dose of 1-2 mg/kg per day of 
prednisone or equivalent).  Taper as 
appropriate.  Treatment with infliximab is 
acceptable per institutional guidelines. 
Grade 3  
Withhold study drug. 
Treatment with systemic corticosteroids 
should be initiated.  Treatment with 
infliximab is acceptable per institutional 
guidelines. 
Grade 4 or recurrent Grade 3 
Permanently discontinue study drug. 
a Criteria for restarting study drug are located in Section 5.8.6. 


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5.8.6.5. 
Immune-Mediated Hepatitis 
Liver chemistry testing (hepatic transaminase and bilirubin levels) should be monitored and 
subjects assessed for signs and symptoms of hepatotoxicity before each dose of INCMGA00012.  
In subjects with hepatotoxicity, infectious or malignant causes should be ruled out, and 
frequency of liver chemistry monitoring should be increased until resolution.  Recommendations 
for management of hepatitis are shown in Table 12. 
Table 12: 
Recommended Approach for Handling Hepatitis 
Study Drug–Associated 
Hepatitis 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action. 
Increase frequency of liver chemistry 
monitoring to twice per week until liver 
chemistry tests return to baseline. 
Grade 2 
Withhold study drug. 
Systemic corticosteroids are indicated 
(initial dose of 0.5-1 mg/kg per day of 
prednisone or equivalent).  Taper as 
appropriate. 
Grades 3 and 4 
Permanently discontinue study drug. 
Treatment with systemic corticosteroids 
should be initiated (initial dose of 1-2 mg/kg 
per day of prednisone or equivalent).  Taper 
as appropriate. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.6.6. 
Immune-Mediated Endocrinopathies 
5.8.6.6.1. Hypophysitis 
Monitor for signs and symptoms of hypophysitis (including hypopituitarism and adrenal 
insufficiency).  Recommendations for management of hypophysitis are shown in Table 13. 
Table 13: 
Recommended Approach for Handling Hypophysitis 
Study Drug–Associated 
Hypophysitis 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action. 
Administer corticosteroids and hormone 
replacement as clinically indicated. 
Grade 2 
Withhold study drug. 
Grade 3 
Withhold or discontinue study drug. 
Grade 4 
Permanently discontinue study drug. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.6.6.2. Thyroid Disorders 
Monitor subjects for changes in thyroid function (at the start of treatment, periodically during 
treatment, and as indicated based on clinical evaluation) and for clinical signs and symptoms of 
thyroid disorders.  Recommendations for management of thyroid disorders are shown in 
Table 14. 


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Table 14: 
Recommended Approach for Handling Thyroid Disorders 
Study Drug–Associated 
Thyroid Disorders 
Withhold/Discontinue Study Druga 
Supportive Care 
Grades 1 and 2 
No action. 
Administer replacement hormones for 
hypothyroidism and manage 
hyperthyroidism with thionamides and 
beta-blockers as appropriate. 
Grade 3 
Withhold or discontinue study drug. 
Grade 4 
Permanently discontinue study drug. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.6.6.3. New Onset Diabetes Mellitus 
Monitor subjects for hyperglycemia or other signs and symptoms of diabetes.  Recommendations 
for management of diabetes mellitus are shown in Table 15. 
Table 15: 
Recommended Approach for Handling New Onset Diabetes Mellitus 
Study Drug–Associated 
Diabetes Mellitus 
Withhold/Discontinue Study Druga 
Supportive Care 
Grades 1 and 2 
No action. 
Intervention not indicated. 
Grade 3 
Withhold study drug. 
Administer insulin for Type 1 diabetes and 
administer antihyperglycemics in subjects 
with severe hyperglycemia. 
Grade 4 
Permanently discontinue study drug. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.6.7. 
Immune-Mediated Nephritis and Renal Dysfunction 
Monitor subjects for changes in renal function.  Recommendations for management of nephritis 
and renal dysfunction are shown in Table 16. 
Table 16: 
Recommended Approach for Handling Nephritis and Renal Dysfunction 
Study Drug–Associated 
Nephritis and Renal 
Dysfunction 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action. 
Intervention not indicated. 
Grade 2 
Withhold study drug. 
Treatment with systemic corticosteroids 
should be initiated (initial dose of 1-2 mg/kg 
per day of prednisone or equivalent).  Taper 
as appropriate. 
Grades 3 or 4 
Permanently discontinue study drug. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.6.8. 
Immune-Mediated Hematologic Toxicities 
Monitor subjects for changes in hematology.  Recommendations for management of 
hematological toxicities are shown in Table 17. 


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Table 17: 
Immune-Mediated Hematologic Toxicities 
Study Drug–Associated 
Hematologic Toxicities 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action 
Intervention not indicated 
Grade 2 
Withhold study drug 
Systemic corticosteroids are indicated 
(initial dose of 0.5-1 mg/kg per day of 
prednisone or equivalent).  Taper as 
appropriate. 
Grade 3 or 4 
Permanently discontinue study drug 
Treatment with systemic corticosteroids 
should be initiated (initial dose of 1-2 mg/kg 
per day of prednisone or equivalent).  Taper 
as appropriate. 
a Criteria for restarting study drug are in Section 5.8.6. 
5.8.6.9. 
Immune-Mediated Skin Reactions 
Immune-mediated rashes, including Stevens-Johnson syndrome, toxic epidermal necrolysis 
(some cases with fatal outcome), exfoliative dermatitis, and bullous pemphigoid, can occur.  
Monitor subjects for suspected severe skin reactions and exclude other causes.  
Recommendations for management of skin reactions are shown in Table 18. 
Table 18: 
Recommended Approach for Handling Skin Reactions 
Study Drug–Associated 
Skin Reactions 
Withhold/Discontinue Study Druga 
Supportive Care 
Grade 1 
No action. 
Intervention not indicated. 
Grade 2 
Withhold study drug. 
Treatment with systemic corticosteroids 
should be initiated (initial dose of 1-2 mg/kg 
per day of prednisone or equivalent).  Taper 
as appropriate. 
Note:  May consider IV immunoglobulin or 
cyclosporine as an alternative or in 
corticosteroid-refractory cases, for Grade for 
SCARs, DIHS/DRESS. 
Grade 3 or suspected 
Stevens-Johnson syndrome 
or toxic epidermal 
necrolysis 
Withhold study drug. 
Grade 4 or confirmed 
Stevens-Johnson syndrome 
or toxic epidermal 
necrolysis 
Permanently discontinue study drug. 
DIHS/DRESS = drug-induced hypersensitivity syndrome/drug reaction with eosinophilia and systemic symptoms; 
SCARs = severe cutaneous adverse reactions syndrome. 
a Criteria for restarting study drug are located in Section 5.8.6. 
5.8.7. 
Permanent Discontinuation of INCMGA00012 Due to Toxicity 
The occurrence of unacceptable toxicity not caused by the underlying disease will require that 
the study treatment be permanently discontinued.  Unacceptable toxicity is defined as follows: 
• Occurrence of a treatment-related AE that, in the judgment of the investigator or the 
sponsor's medical monitor, compromises the subject's ability to continue 
study-specific procedures or is considered to not be in the subject's best interest. 
• Persistent treatment-related AE requiring a delay of therapy for more than 12 weeks. 
• Any AE defined in the dose modifications management guidelines (see Section 5.8.6) 
requiring the study treatment be discontinued. 


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5.9. 
Withdrawal of Subjects From Study Treatment 
5.9.1. 
Withdrawal Criteria 
Subjects must be withdrawn from study treatment for the following reasons: 
• Further treatment would be injurious to the subject's health or well-being, in the 
investigator's medical judgment.  Subject should still be followed for disease 
progression and survival. 
• The subject becomes pregnant. 
• Consent is withdrawn.  NOTE:  Subjects may choose to discontinue study treatment 
and remain in the study to be followed for disease progression and survival. 
• The study is terminated by the sponsor. 
• The study is terminated by the local health authority, IRB, or IEC. 
• Unacceptable toxicity (Section 5.8.4) has occurred. 
• Disease progression has occurred.  NOTE:  A subject may be allowed to continue 
receiving study drug if the investigator believes that the subject is receiving clinical 
benefit and no other treatment options are available for the subject. 
A subject may be withdrawn from the study as follows: 
• If, during the course of the study, a subject is found not to have met eligibility 
criteria, the medical monitor, in collaboration with the investigator, will determine 
whether the subject should be withdrawn from the study.  See Section 11.3, Protocol 
Adherence.  This includes cases where the local genomic testing results are positive 
for an FGF/FGFR alteration, but the central genomic testing is not. 
• If a subject is noncompliant with study procedures or study drug administration in the 
opinion of the investigator, the sponsor should be consulted for instruction on 
handling the subject. 
5.9.2. 
Withdrawal Procedures 
Once the decision is made to permanently discontinue the study drug, the following steps should 
be followed: 
• The study monitor or sponsor must be notified. 
• The reasons for withdrawal and the date of last dose of study drug must be 
documented in the subject's medical record and CRF (case report form). 
• The EOT visit should be performed. 
• Subjects must be followed for safety through the time of the follow-up visit or until 
study drug–related toxicities resolve, return to baseline, or are deemed irreversible, 
whichever is longer. 
Reasonable efforts should be made to have the subject return for a follow-up visit.  These visits 
are described in Section 6. 


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5.10. 
Concomitant Medications and Measures 
The following must be recorded in the subject's medical record and CRF from the time of 
signing consent through and including the 30 days from date of last dose of study drug: 
• All concomitant medications and treatments. 
• Any prior medication received up to 30 days before enrollment (Cycle 1 Day 1). 
• Concomitant treatments and/or procedures that are required to manage a subject's 
medical condition during the study. 
5.11. 
Restricted Medications and Measures 
The use of mild or moderate CYP inhibitors or mild inducers should involve careful monitoring.  
It is recommended that additional PK samples be obtained when such agents are coadministered 
with INCB054828, using the same PK sampling schedule as in Cycle 1 Day 14. 
Calcium-based phosphate-binding medications are not recommended due to a concern for 
potential of soft tissue mineralization.  Aluminum-based phosphate binders are not recommended 
due to potential toxicities associated with use. 
5.12. 
Prohibited Medications and Measures 
The following medications and measures are prohibited: 
• The concomitant administration of potent CYP3A4 inhibitors and inducers and 
moderate CYP3A4 inducers is prohibited.  Based on the low overall bioavailability of 
topical ketoconazole, there are no restrictions on topical ketoconazole. 
• Any concomitant use of a selective FGFR inhibitor is prohibited. 
• Investigational study drug for any indication is prohibited. 
• Use of any anticancer medications other than the study medication from 21 days 
before Day 1 is prohibited. 
• Subjects receiving pembrolizumab and INCMGA00012:  Live vaccines within 
28 days before first administration of study drug, throughout the treatment phase of 
the study, and for a duration of 90 days after the last dose of study drug. 
6. 
STUDY ASSESSMENTS 
For instructions on study assessments, see Section 7.  All study assessments will be performed as 
outlined in Table 19 and Table 20.  Required analytes are shown in Table 21 (all indications) and 
Table 22 (multiple myeloma). 


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Table 19: 
Schedule of Assessments 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Post-Treatment 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
Safety 
Follow-Up 
Disease 
Status 
Follow-Up 
Survival 
Follow-Up 
D1 D2 D8 D14 D15 D16 D1 
D8 
D15 
Food Effect 
(Part 2 Only) 
D1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
57 Days 
(± 5 Days) 
After D/C 
Every 
12 Weeks 
(± 7 Days) 
Informed 
consent 
7.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Contact IRT  
7.2 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Inclusion/ 
exclusion criteria 
3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/cancer 
history 
7.3.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications 
7.3.2, 7.3.3 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
INCB054828 in 
clinic 
5.1.1 
 
X X 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Gem + CIS in 
clinic 
5.1.2 
 
X 
 
X 
 
 
 
X 
X 
 
 
 
X 
 
 
 
 
 
Docetaxel in 
clinic 
5.1.3 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
Pembrolizumab 
in clinic 
5.1.4 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
Trastuzumab in 
clinic 
5.1.5 
 
X 
 
 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
 
INCMGA00012 
in clinic 
5.1.6 
 
X 
 
 
 
 
 
X* 
 
 
 
 
X* 
 
 
 
 
*Based on 
Q4W regimen 
New anticancer 
therapy  
6.4.2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Survival status 
6.4.3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
Comprehensive 
PE  
7.4.2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
 
Targeted PE 
7.4.3 
 
X 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 


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Table 19: 
Schedule of Assessments (Continued) 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Post-Treatment 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
Safety 
Follow-Up 
Disease 
Status 
Follow-Up 
Survival 
Follow-Up 
D1 D2 D8 D14 D15 D16 D1 
D8 
D15 
Food Effect 
(Part 2 Only) 
D1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
57 Days 
(± 5 Days) 
After D/C 
Every 
12 Weeks 
(± 7 Days) 
ECOG 
7.6.1 
X 
X X 
X 
X 
 
 
X 
 
 
X 
 
X 
X 
 
 
 
 
Vital 
signs/weight  
7.4.4 
X 
X X 
X 
X 
X 
 
X 
 
 
X 
 
X 
X 
X 
 
 
 
12-lead ECG 
(triplicate) 
(anytime) 
7.4.5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
12-lead ECG 
(triplicate) 
(predose) 
7.4.5 
Table 23 
 
X 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Approximately 
5 minutes 
before the 
predose PK 
blood draw 
12-lead ECG 
(triplicate) 
(postdose) 
7.4.5 
Table 23 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
1, 2, and 
4 hours 
postdose 
approximately 
5 minutes 
before the PK 
blood draw 
Echo/MUGA  
7.4.6 
X 
 
 
 
 
 
 
X 
 
 
 
 
X 
X 
 
 
 
Only subjects 
taking 
trastuzumab. 


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Table 19: 
Schedule of Assessments (Continued) 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Post-Treatment 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
Safety 
Follow-Up 
Disease 
Status 
Follow-Up 
Survival 
Follow-Up 
D1 D2 D8 D14 D15 D16 D1 
D8 
D15 
Food Effect 
(Part 2 Only) 
D1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
57 Days 
(± 5 Days) 
After D/C 
Every 
12 Weeks 
(± 7 Days) 
Eye examination 
(including slit 
lamp, visual 
acuity, 
fundoscopy with 
digital imaging, 
and optic 
coherence 
tomography) 
7.4.7 
X 
 
 
 
 
 
 
X* 
 
 
 
 
X* 
X 
 
 
 
*Every 
3 cycles 
starting with 
Cycle 3 
(± 14 days). 
Adverse events 
7.4.1 
X 
X X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
Tumor tissue 
7.5, 7.8.4 
X 
 
 
 
 
 
 
X* 
 
 
 
 
 
X* 
 
 
 
*Refer to 
Section 7.8.4 
for details. 


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Table 19: 
Schedule of Assessments (Continued) 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Post-Treatment 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
Safety 
Follow-Up 
Disease 
Status 
Follow-Up 
Survival 
Follow-Up 
D1 D2 D8 D14 D15 D16 D1 
D8 
D15 
Food Effect 
(Part 2 Only) 
D1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
57 Days 
(± 5 Days) 
After D/C 
Every 
12 Weeks 
(± 7 Days) 
Disease 
assessment 
6.4.2, 7.5, 
Appendix D, 
Appendix E 
X* 
 
 
 
 
 
 
X** 
 
 
 
 
X** 
X 
 
X 
 
*Multiple 
myeloma 
subjects; 
initial 
assessment 
28 days before 
C1D1. 
**Solid 
tumors:  every 
3 cycles 
starting at the 
end of 
Cycle 3. 
Skeletal survey 
(multiple 
myeloma only) 
Appendix D 
X 
 
 
 
 
 
 
X* 
 
 
 
 
 
 
 
 
 
*Every 
8 weeks after 
baseline. 
D/C = discontinuation; PE = physical examination. 


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Table 20: 
Laboratory Assessments 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Safety 
Follow-Up 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
D1 
D2 
D8 
D14 D15 D16 
D1 
D8 
D15 
Food Effect 
(Part 2 
Only) 
Day 1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
± 3 
Days 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
Comprehensive serum 
chemistry 
7.4.8.1 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
Hematology with differential 
7.4.8.1 
X 
X 
X 
X 
 
X 
 
X 
X 
X 
 
X 
X 
X 
X 
 
Coagulation panel 
7.4.8.1 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Lipid panel 
7.4.8.1 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
 
Parathyroid hormone 
7.4.8.1 
X 
X 
 
 
 
 
 
X 
 
 
 
 
X 
X 
X 
 
Urinalysis 
7.4.8.2 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Serum or urine pregnancy 
test 
7.4.8.3 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Serology 
7.4.8.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Total urine  
7.7.3 
 
 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Cytogenetics (MPN only) 
Appendix E 
X 
 
 
 
 
 
 
X* 
 
 
 
 
 
X 
 
*As needed. 
Serum protein 
electrophoresis, urine 
protein electrophoresis, 
quantitative 
immunoglobulins, serum 
free light chains (multiple 
myeloma only) 
Appendix D 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
Beta-2 microglobulin 
(multiple myeloma only) 
Appendix D 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
 
 
JAK-2 mutation (MPN only) Appendix E 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pharmacokinetic sampling 
7.7 
 
X 
X 
X 
X 
X 
X 
 
 
 
X* 
X* 
 
 
 
*Part 2 food 
effect only. 


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Table 20: 
Laboratory Assessments (Continued) 
Procedure 
Protocol 
Section 
Screening 
Treatment Phase 
EOT 
Safety 
Follow-Up 
Notes 
Cycle 1 
Cycles 2-6 
Cycle 2 
Cycles 
7+ 
D1 
D2 
D8 
D14 D15 D16 
D1 
D8 
D15 
Food Effect 
(Part 2 
Only) 
Day 1 
D14 
D15 
Days -28 
to -1 
 
 
± 3 
Days 
 
 
 
± 3 
Days 
± 3 
Days 
± 3 
Days 
 
 
± 3 
Days 
+ 5 
Days 
30 Days 
(+ 5 Days) 
After EOT 
PK plasma protein binding 
(postdose) 
7.7.3 
 
X 
 
 
X 
 
 
X* 
X* 
X* 
 
 
 
 
 
Renally impaired 
subjects; PK 
blood sample for 
determination of 
plasma protein 
binding will be 
obtained at 
4 hours postdose. 
*BID dosing:  
testing Days 1, 8, 
and 15 through 
end of  Cycle 3. 
Tissue biopsy 
7.8.4 
X 
 
 
 
 
 
 
X* 
 
 
 
 
X 
X** 
 
*At least 
1 on-treatment 
biopsy. 
**EOT biopsy 
requested but not 
required. 
 


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Table 21: 
Laboratory Tests:  Required Analytes for All Indications 
Serum Chemistry 
Hematology 
Other  
Albumin 
Amylase 
Alkaline phosphatase 
ALT 
AST 
Bicarbonate 
Blood urea nitrogen or urea 
Calcium 
Chloride 
Creatinine 
Glucose 
Lactate dehydrogenase 
Lipase 
Phosphate 
Potassium 
Sodium 
Total bilirubin 
Direct bilirubin (if total 
bilirubin is elevated above 
ULN) 
Total protein 
Uric acid 
Vitamin D (25-
hydroxyvitamin D and 
1,25-dihidroxyvitamin D) 
Complete blood count, 
including the following: 
Hemoglobin 
Hematocrit 
Platelet count 
Red blood cell count 
White blood cell count 
 
Differential count, including 
the following: 
Basophils 
Eosinophils 
Lymphocytes 
Monocytes 
Neutrophils 
 
Absolute values must be 
provided for the following: 
WBC differential laboratory 
results: 
Lymphocytes 
Neutrophils 
Serology: 
Hepatitis B surface antigen/antibody 
Hepatitis B core antibody 
HCV antibody 
NOTE:  If any of the above are positive, 
HBV-DNA, HCV-RNA to assess risk of 
reactivation. 
Pregnancy test:   
Female subjects of childbearing potential only 
require a serum test at screening and a urine 
pregnancy test before the first dose on Cycle 1 
Day 1 and at EOT. 
Pregnancy tests (serum or urine) should be 
repeated if required by local regulations. 
Urinalysis with microscopic examination: 
Color and appearance 
pH and specific gravity 
Bilirubin 
Glucose 
Ketones 
Leukocytes 
Nitrite 
Occult blood 
Protein 
Urobilinogen (optional) 
Coagulation: 
PT 
PTT or aPTT 
INR 
Endocrine Monitoring 
Lipid Panel 
Subjects With Myeloproliferative Neoplasm 
Parathyroid hormone 
Total Cholesterol 
Triglycerides 
LDL 
HDL 
Bone marrow aspirate and biopsy 
JAK-2 mutation status 
Cytogenetics 
aPTT = activated partial thromboplastin time. 
Table 22: 
Laboratory Tests:  Required Analytes for Multiple Myeloma Subjects 
Laboratory Test 
Serum protein electrophoresis and immunofixation (M protein quantification) 
Urine protein electrophoresis (M protein quantification) 
Quantitative immunoglobulins 
Serum-free light chains 
Beta-2 microglobulin 
Bone marrow aspirate and biopsy 
FISH 
Cytogenetics 


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6.1. 
Screening Phase 
Prescreening is allowed for subjects without genomic testing results (Part 2 and Part 3).  For 
subjects not requiring a genomic testing report (Part 1) or having a genomic testing report for 
Part 2 or 3, the screening phase will be up to 28 days.  The screening phase is the interval 
between the signing of the informed consent form (ICF) and the first dose of study drug (Cycle 1 
Day 1).  Informed consent must be obtained before performing any study-specific procedures.  
Assessments that are required to demonstrate eligibility may be performed over the course of 
1 or more days during this phase. 
Results from the screening visit evaluations will be reviewed to confirm subject eligibility before 
randomization or the administration of study drug.  Tests with results that fail eligibility 
requirements may be repeated once during the screening phase if the investigator believes the 
results to be in error.  Additionally, a subject who fails screening may repeat the screening 
process 1 time if the investigator believes that there has been a change in eligibility status 
(eg, following recovery from an infection). 
Additionally, the screening phase will be utilized to determine the baseline assessments of 
clinical condition and disease status.  Tumor assessments appropriate to the type of malignancy 
will be performed and recorded in the CRF. 
6.2. 
Treatment Phase 
The treatment begins on the day the subject receives the first dose of study drug; this is defined 
as Cycle 1 Day 1 through the point at which the PI determines the subject will be permanently 
discontinued from study drug.  Dates for subsequent study visits will be determined based upon 
this day and should occur within 3 days (+/-) of the scheduled date unless delayed for safety 
reasons.  At Cycle 1 Day 1, results from screening visit evaluations should be reviewed to 
determine if the subject continues to meet the eligibility requirements as specified in the 
Protocol. 
During the treatment phase, regular study visits (physician visits) will occur during the first 
6 treatment cycles (ie, Days 1, 2, 8, 14, 15, and 16 of Cycle 1) and thereafter at the beginning of 
each 21-day treatment cycle, provided that subjects do not have more than a stable Grade 2 
toxicity and have obtained approval from the medical monitor. 
At certain study visits as indicated in Table 20, subjects will attend the study visit having fasted, 
having recorded the time of the prior study drug administration and time of last meal, and having 
withheld the dose of the study drug.  At these visits, PK and/or PD sampling will be conducted. 
6.3. 
End of Treatment 
Once a decision is made that the subject will permanently discontinue study drug, the EOT visit 
should be conducted.  If the EOT visit coincides with a regular study visit, the EOT evaluations 
will supersede those of that scheduled visit, and the data should be entered in the EOT page in 
the CRF.  The subject should be encouraged to return for the follow-up visit. 


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6.4. 
Follow-Up Phase 
6.4.1. 
Safety Follow-Up 
The safety follow-up phase is the interval between the EOT visit and the scheduled safety 
follow-up visit.  Adverse events and SAEs must be reported up until at least 30 days after the last 
dose of study drug, the date of the safety follow-up visit, or until study drug–related toxicities 
resolve, return to baseline, or are deemed irreversible, death, or initiation of a new anticancer 
treatment, whichever occurs first.  Reasonable efforts should be made to have the subject return 
for the follow-up visit and report any AEs that may occur during this phase.  If the subject is 
unable to return to the site for the 30-day safety follow-up visit, a follow-up phone call can be 
conducted by the site at the time of the scheduled 30-day safety follow-up visit to collect any 
new safety information that occurred between EOT and the safety visit.  If a subject is planned to 
start new anticancer therapy before the end of the 30-day safety follow-up period, the safety 
follow-up visit should be performed before the initiation of the new anticancer therapy.  Once 
new anticancer therapy has been initiated, the subject will move into the survival follow-up 
phase. 
6.4.2. 
Disease Status Follow-Up 
Subjects who discontinue study treatment for a reason other than disease progression will move 
into the disease status follow-up phase and should be assessed every 57 ± 5 days by radiologic 
imaging (or by the relevant disease response assessment) to monitor disease status.  Every effort 
should be made to collect information regarding disease status until: 
• The start of new antineoplastic therapy 
• Disease progression 
• Death 
• End of the study 
6.4.3. 
Survival Follow-Up 
Once a subject has confirmed disease progression or starts a new anticancer therapy, the subject 
moves into the survival follow-up phase and should be contacted by telephone, email, or visit at 
least every 12 weeks to assess for survival status until death, withdrawal of consent, or the end of 
the study, whichever occurs first. 
6.5. 
Unscheduled Visits 
Unscheduled visits may occur at any time as medically warranted.  Any assessments performed 
during those visits should be recorded in the CRF. 
6.6. 
Beginning and End of Study 
The study begins when the first subject signs the informed consent.  The end of the study may be 
designated as the timepoint when all subjects have discontinued the study or the sponsor 
terminates the study. 


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7. 
CONDUCT OF STUDY ASSESSMENTS AND PROCEDURES 
7.1. 
Administration of Informed Consent Form 
Valid informed consent must be obtained from the study subject before conducting any 
study-specific procedures.  The granting of informed consent for study participation must be 
documented in writing, using an ICF that contains all the elements required by ICH E6 and 
describes the nature, scope, and possible consequences of the study in a form understandable to 
the study subject.  Local and institutional guidelines for ICF content and administration must be 
followed; a copy of the signed ICF must be provided to the study subject.  Subjects of 
childbearing potential must agree to take appropriate measures to avoid pregnancy in order to 
participate in the study (Appendix A). 
7.2. 
Interactive Response Technology Procedure 
The Interactive Response Technology (IRT) will be contacted by the site to obtain a subject ID 
number when a subject enters the screening phase.  Upon determining that the subject is eligible 
for study entry, IRT will be contacted to obtain study drug assignment.  Additionally, IRT will 
be contacted on Day 1 of each regular study visit to register the subject visit and update the study 
drug supply. 
7.3. 
Demography and History 
7.3.1. 
Demographics and Medical History 
Demographic data and a complete medical and medication history will be collected at screening 
by the investigator or qualified designee and will include date of birth, race, ethnicity, medical 
and surgical history, and concurrent illnesses assessed using the NCI CTCAE v4.03 (NCI 2010).  
Medical history should include all active conditions and any condition diagnosed within the prior 
10 years that are considered to be clinically significant by the investigator.  Details regarding 
the disease for which the subject has enrolled in this study (eg, date of diagnosis, primary 
tumor histology, prior systemic therapies, surgeries, radiation therapy, and stage of cancer) will 
be recorded separately and not listed in medical history. 
7.3.2. 
Prior Medications 
Prior and ongoing medications will be reviewed to determine study eligibility.  The investigator 
or qualified designee will review prior medication use, including any Protocol-specified washout 
requirement, and record prior medication taken by the subject within 28 days before starting the 
study.  Treatment for the disease for which the subject has enrolled in this study will be recorded 
separately and not listed as a prior medication. 
7.3.3. 
Concomitant Medications 
The investigator or qualified designee will record medication, if any, taken by the subject during 
the study.  Concomitant medications include any prescription, over-the-counter, or natural/herbal 
preparations taken or administered during the study period.  All medications related to reportable 
SAEs should be recorded as defined in Section 8.1.1. 


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7.4. 
Safety Assessments 
7.4.1. 
Adverse Events 
Adverse events will be monitored from the time the subject signs the ICF.  Subjects will be 
instructed to report all AEs during the study and will be assessed for the occurrence of AEs 
throughout the study.  In order to avoid bias in eliciting AEs, subjects will be asked general, 
nonleading questions such as "How are you feeling?"  All AEs (serious and nonserious) must be 
recorded on the source documents and CRFs regardless of the assumption of a causal 
relationship with the study drug or the combination agents.  The definition, reporting, and 
recording requirements for AEs are described in Section 8. 
7.4.2. 
Comprehensive Physical Examination 
Physical examinations must be performed by a medically qualified individual such as a licensed 
physician, Physician's Assistant, or an advanced Registered Nurse Practitioner, as local law 
permits. 
The comprehensive physical examination should include the following organ or body system 
assessments:  skin; head, eyes, ears, nose, and throat; thyroid; lungs; cardiovascular system; 
abdomen (liver, spleen); extremities; lymph nodes; and a brief neurological examination.  Before 
the first dose of study treatment, clinically significant abnormal findings should be recorded as 
medical history.  After the first dose of study treatment, new clinically significant abnormal 
findings should be recorded as AEs.  
7.4.3. 
Targeted Physical Examination 
A targeted physical examination will be a symptom-directed evaluation conducted by the 
investigator or designee.  The targeted physical examination will include assessment(s) of the 
body systems or organs, as indicated by subject symptoms, AEs, or other findings.  If the subject 
does not report any symptoms, then a targeted physical examination is not required. 
7.4.4. 
Vital Signs 
Vital sign measurements (blood pressure, heart rate, respiratory rate, and body temperature) will 
be taken with the subject in the recumbent, semirecumbent, or sitting position after 
approximately 5 minutes of rest.  Height will be measured at screening only. 
7.4.5. 
Twelve-Lead Electrocardiograms 
Triplicate 12-lead ECGs will be obtained on the days and times noted in the schedule of 
assessments (Table 19) and Table 23 below.  All timed 12-lead triplicate ECGs will be 
conducted predose and then at 1, 2, and 4 hours postdose, approximately 5 minutes before the 
PK blood draw at the corresponding timepoint.  The specified postdose timepoint may be 
adjusted based on emerging PK data.  All 12-lead ECGs will be performed with the subject in a 
recumbent or semirecumbent position after approximately 5 minutes of rest.  Baseline ECG 
intervals will be equal to the average of all ECG intervals obtained before the first study drug 
dose administration.  All 12-lead ECGs obtained at subsequent timepoints during the study will 
be compared with these baseline 12-lead ECG intervals.  For ECG morphology, the ECG 
performed closest to the time of administration on Day 1 of Cycle 1 will be used as the baseline. 


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Twelve-lead ECGs will be acquired using an ECG analysis system with analysis and printing 
capabilities, as well as digital transmission capabilities to a central capture module at the central 
ECG laboratory.  The investigator and research staff will receive adequate training by a qualified 
person on the use and operation of the analysis system.  The successful digital submission of a 
12-lead ECG, meeting quality standards, to the central ECG laboratory by the site must be 
ensured before enrollment of the first subject.  The study manual for procedures that must be 
followed for the recording and transmission of ECGs and the operator's manual with instructions 
for operating the digital capture module will be shipped to the site along with the device.  The 
12-lead ECGs will be interpreted by the investigator at the site and will be used for immediate 
subject management.  The decision to include or exclude a subject or discontinue a subject's 
participation in the study based on an ECG flagged as "Abnormal, Clinically Significant" is the 
responsibility of the investigator, in consultation with the sponsor's medical monitor, as 
appropriate.  Twelve-lead ECGs that are identified by the investigator as "Abnormal, Clinically 
Significant" will be sent to the sponsor's medical monitor for review. 
The overall ECG interpretation will be indicated by a flagging system that will help distinguish 
between a normal ECG, ECG abnormalities where no further investigation is required, and ECG 
abnormalities where study exclusion, further cardiovascular investigation, and/or prompt action 
may be necessary depending on the clinical context.  A suitable flag will be included in the 
"Overall ECG Interpretation" section of the report when an ECG is considered to be technically 
unacceptable or uninterpretable.  If several different abnormalities exist corresponding to 
different levels of flagging, the label will reflect the most severe level.  Flagging by the central 
expert cardiologist of these significant abnormalities should only be regarded as a suggestion.  
This service is intended to assist the investigator in his/her interpretation of the ECG and 
decision-making.  It is not intended to replace the investigator's expert judgment and knowledge 
of the subject's medical condition. 
Table 23: 
Electrocardiogram Timed Measurements 
Study Time 
Timing of ECG 
Cycle 1, Day 1 
• 
Predosea 
• 
1, 2, and 4 hours postdoseb 
Cycle 1, Day 8 
• 
Predosea 
Cycle 1, Day 14 
• 
Predosea 
• 
1, 2, and 4 hours postdoseb 
a Approximately 5 minutes before the predose PK blood draw. 
b Approximately 5 minutes before the respective postdose PK blood draw. 
7.4.6. 
Echocardiogram/Multigated Acquisition Scan 
An echocardiogram/MUGA scan will be required only for subjects enrolling in the Part 3 
trastuzumab group.  Subjects will need this completed before enrollment (screening) and then on 
Day 1 of every cycle and at EOT. 


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7.4.7. 
Comprehensive Eye Examination 
A comprehensive eye examination should be performed by a qualified ophthalmologist at 
screening, once every 3 cycles (± 14 days, starting at Cycle 3), at EOT, and as clinically 
indicated.  The eye examination should include a visual acuity test, slit-lamp examination, 
funduscopy with digital imaging, and optic coherence tomography.  Every effort should be made 
to ensure that all subsequent examinations are performed by the same ophthalmologist. 
7.4.8. 
Laboratory Assessments 
A laboratory local to the study site and subject may perform all clinical laboratory assessments 
for safety (eg, serum chemistry, hematology assessments, and urinalysis).  The investigative site 
will enter the local laboratory results and laboratory normal ranges into the CRF.  All local 
laboratory assessments should be performed using standard procedures on the days indicated in 
Table 20.  Table 22 lists the required laboratory tests for multiple myeloma subjects, and 
Table 21 lists the required laboratory tests for all other indications.  Additional tests may be 
performed if clinically indicated.  Subjects who have abnormal on-study calcium and phosphorus 
levels should have their levels monitored at least twice a week. 
Laboratory tests for screening should be performed within 14 days before the first dose of 
treatment.  Predose laboratory procedures can be conducted up to 72 hours before study drug 
administration.  Results must be reviewed by the investigator or qualified designee and found to 
be acceptable before starting study treatment. 
7.4.8.1. 
Chemistry, Hematology, Coagulation Panel, Fertility, Serology, and Endocrine 
Function Testing 
Chemistry, hematology, coagulation panel, serology, and endocrine function will all be analyzed 
by the local site laboratory. 
7.4.8.2. 
Urinalysis 
Urinalysis will be analyzed by the local site laboratory. 
7.4.8.3. 
Pregnancy Testing 
Serum pregnancy tests will be analyzed by the site laboratory at screening.  Subsequently, 
pregnancy tests (either serum or urine) may be conducted as medically indicated or as required 
per local guidelines. 
If a subject inadvertently becomes pregnant while on treatment with INCB054828, the subject 
will immediately be withdrawn from the study.  The site will contact the subject at least monthly 
and document the subject's status until the pregnancy has been completed or terminated.  The 
outcome of the pregnancy will be reported to the sponsor without delay and within 24 hours if 
the outcome is an SAE (eg, death, abortion, congenital anomaly, or other disabling or 
life-threatening complication to the mother or newborn).  The study investigator will make every 
effort to obtain permission to follow the outcome of the pregnancy and report the condition of 
the fetus or newborn to the sponsor.  If a male subject impregnates his female partner, the study 
personnel at the site must be informed immediately and the pregnancy reported to the sponsor 
and followed as described above and in Section 8. 


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7.4.9. 
Evaluation of FGF and FGFR Genetic Alterations 
Subjects may be evaluated for FGF and FGFR alterations by the investigational site's local 
sequencing laboratory (eg, FISH, immunohistochemistry, sequencing, next-generation 
sequencing, or gene expression analyses).  All subjects will have a retrospective analysis 
conducted by the sponsor's designated central laboratory assay if it was not utilized initially for 
confirmation of study eligibility in Part 2 and Part 3 (dose expansion).  If the FGFR/FGF genetic 
alteration cannot be confirmed in subjects in Part 2 and Part 3 (dose expansion), additional 
subjects may be enrolled as replacements.  The continuation of the treatment in subjects with 
discordant tumor genetic information will be at the investigator's discretion. 
7.5. 
Efficacy Assessments 
Objective assessment of tumor status is required using appropriate disease-specific techniques 
and the investigator's assessment will be used to determine responses and will be logged into the 
CRF.  For solid tumors, the RECIST 1.1 (Eisenhauer et al 2009) will be used and the 
recommended method for measuring and following tumor burden will be computed tomography 
(CT) scan, to include the thorax, abdomen, pelvis, and neck if needed.  Alternative modalities 
may be substituted for a CT scan at the discretion of the investigator, provided that the same 
modality is used throughout the study and the methodology is consistent with RECIST 1.1. 
For subjects with multiple myeloma, the assessments will be based on the IMWG Multiple 
Myeloma response criteria, see Appendix D (Durie et al 2006). 
For subjects with MPNs, the response criteria in Appendix E will be used to assess response. 
The schedule for efficacy assessments will be at screening (this will be considered the baseline 
scan) and every 3 cycles (starting with Cycle 3) throughout the study.  Efficacy assessments 
should occur at the end of the cycle.  Multiple myeloma subjects should have response 
assessments performed around Day 14 of every cycle (± 2 days).  Subjects with MPN should 
have a bone marrow aspirate and biopsy performed approximately 3, 6, and 12 months after 
Day 1 and then every 12 months on the nearest Cycle Day 14 (± 2 days) after the first dose of 
treatment and as clinically indicated.   
For subjects who discontinue treatment for reasons other than disease progression, every effort 
should be made to continue monitoring disease status until (1) start of new antineoplastic 
therapy, (2) documented disease progression, (3) death, or (4) the end of study, whichever occurs 
first. 
7.6. 
Performance and Quality of Life Assessments 
7.6.1. 
Eastern Cooperative Oncology Group Performance Status 
The investigator or qualified designee will assess ECOG performance status (Appendix C) at 
screening and before the administration of each cycle of study treatment in the clinic and EOT as 
specified in the schedule of assessments (Table 19).  No quality-of-life instrument will be used in 
this study. 


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7.7. 
Pharmacokinetic Assessments 
7.7.1. 
Blood Sample Collection 
Pharmacokinetic samples will be obtained at the visits indicated in Table 20, and collection times 
and windows are described in Table 24 and Table 25.  The exact date and time of the PK blood 
draws will be recorded in the CRF along with the date and time of the last dose of study drug 
preceding the blood draw and the time of the most recent meal.  Instructions for sample 
preparation and shipping will be provided in the Laboratory Manual.  Subjects will receive 
reminder cards/diaries in advance of the study visit providing instruction to hold the dose of 
study drug on the day of the visit, a place to record the time of the prior dose of study drug, and a 
place to record the time of the most recent meal or snack consumed. 
During Cycle 1, PK samples will be obtained on Days 1, 2, 8, 14, 15, and 16.  On these 
designated days, study subjects will refrain from eating 8 hours prior to arriving at the research 
unit.  A trough (predose) PK sample will be drawn early in the study visit; the sample must be 
drawn approximately 1 hour prior to study drug administration.  Subjects then need to fast for 
1 additional hour after taking study medication.  Once the subject takes the study drug, any 
subsequent timed samples will be taken. 
Subjects on the BID dosing schedule will have PK sampling performed as indicated above 
during Cycle 1, but additional PK samples will be drawn on Day 1, Day 8, and Day 15 of Cycles 
2 and 3 (predose only). 
7.7.2. 
Food-Effect Study (Part 2 Only) 
This cohort is closed to enrollment, as of Protocol Amendment 8. 
On Cycle 2 Day 14, only study subjects who are selected to participate in the food-effect study in 
the expansion (Part 2, n ≈ 8) will be required to undergo PK testing in a fed state. 
• Pharmacokinetic testing conducted on Cycle 2 Day 14 will be similar to that on 
Cycle 1 Day 14 with respect to the timing of sample collection and evaluations.  
Subjects may be excused from the food-effect part of the study if they are unable to 
consume the meal or feel they are unable to consume the meal. 
• Subjects receiving INCB054828 in the fed state will have been fasted from food 
(not including water) overnight for at least 8 hours.  A standardized high-fat, 
high-calorie breakfast will be given to these subjects approximately 30 minutes 
before administration of study drug.  Subjects must consume the entire breakfast 
within 25 minutes, and study drug administration will begin 5 minutes after 
completing breakfast. 
• The high-fat, high-calorie breakfast (50% kcal from fat) will consist of: 
− 2 eggs fried in butter 
− 2 strips of bacon 
− 1 English muffin with butter 
− 4 oz hash brown potatoes 
− and 8 oz whole milk 








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7.8.4. 
Tumor Biopsy 
Subjects must have an archival tumor biopsy sample (obtained within the last 2 years) available 
or be willing to undergo a pretreatment tumor biopsy at baseline.  For Part 1 subjects, fresh 
tumor biopsies for the purpose of determining study eligibility should be limited to tumors where 
tissue can be safely accessed.  The medical monitor should be contacted to determine the 
potential risk of a tumor biopsy.  Details and methods for obtaining, processing, and shipping the 
fresh tumor biopsy samples and for processing and shipping the archived tumor tissue samples 
will be provided in the Laboratory Manual for the study. 
Tumor lesions used for biopsy should not be selected as RECIST target lesions, unless there are 
no other lesions suitable.  If a RECIST target lesion is used for biopsy, the lesion must be ≥ 2 cm 
in the longest diameter. 
The constituents of the tumor as well as the tumor microenvironment may be examined by 
histology, immunohistochemistry (using markers of cell populations, growth, signaling, cell 
cycling, apoptosis, etc.), and other exploratory methods, including analysis of RNA-based 
transcriptional profiles and somatic mutations to identify characteristics that may be associated 
with safety, response, or resistance to treatment with the study drug.  Potential somatic mutations 
in tumor samples may be confirmed by assessing the specific sequence change in a normal 
sample obtained by buccal swab.  These analyses will be conducted by Incyte Corporation 
(Wilmington, DE) or Incyte's designee. 
Optional tumor biopsy specimens:  May be obtained while the subject is receiving study drug 
in subjects with accessible tumors to assess intratumoral changes that might be associated with 
safety, response, or resistance to treatment. 
Mandatory tumor biopsy specimens:  Biopsies are mandatory for any subjects enrolled a lower 
dose level cohort in Part 1 or Part 3 or Part 2 (tumor-specific cohorts).  A baseline biopsy 
(performed any time after last treatment) and at least 1 on-treatment biopsy (recommended at 
Cycle 2 Day 14, but allowed to be performed at any cycle; must be performed on a study drug 
administration day, preferably between Day 8 and Day 14).  Additionally, an EOT/at time of 
progression biopsy is requested but not required.  
 
  NOTE:  Subjects who withdraw consent for mandatory biopsy after enrollment will 
be reported as a Protocol deviation. 
7.9. 
Other Study Procedures 
7.9.1. 
Administration of INCB054828 
Subjects will self-administer INCB054828 orally, with water, QD on a 2-week on-therapy and 
1-week off therapy schedule, as directed by the investigator.  Study drug can be taken with or 
without food. 
Subjects enrolled in the continuous administration cohort(s) will take INCB054828 orally with 
water QD for the 21-day administration cycle, as directed by the investigator. 
Study drug will be administered in the study clinic on days as indicated in Table 19, and 
Section 7.7.1; subjects will attend the study visit having fasted, having recorded the time of the 
prior administration of study drug and prior meal, and having withheld the dose of study drug.  
At this visit, PK and PD sampling will be conducted. 


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7.9.2. 
Dispensing of INCB054828 
An initial bulk supply of INCB054828 will be provided to investigative sites prior to enrollment 
of the first subject.  Thereafter, the site staff will contact the sponsor for resupply of 
INCB054828.  When dispensing to subjects, the investigator or designee will remove the 
appropriate quantity of study drug from their stock, dispense the medication, and enter the 
amount dispensed into the CRF and drug accountability log.  Full details will be provided in the 
Study Manual. 
7.9.3. 
Assessment of Compliance With INCB054828 
The study subject will return all full, empty, and opened/partially used bottles of study drug at 
the beginning of each treatment cycle, and a compliance check (tablet count) will be performed 
by the clinic staff at each visit; therefore, appropriate steps should be taken to optimize 
compliance. 
7.9.4. 
Distribution of Subject Reminder Cards 
Subjects will be provided with subject reminder cards at each visit.  The subject reminder cards 
will indicate the date and time of the next visit.  The reminder cards will have a field for the 
subject to enter the date and time of the last dose taken before the visit and to record the time of 
the last meal.  Reminder cards will include instructions specific to study visits when the PK/PD 
sample is collected, at which time the subject will refrain from taking the study drug at home in 
the morning prior to the clinic visit.  All necessary instructions, such as those for study drug 
administration, concomitant medications, and laboratory tests should be provided to the subject 
in writing on this reminder card or on accompanying written materials. 
8. 
SAFETY MONITORING AND REPORTING 
8.1. 
Adverse Events 
8.1.1. 
Definitions and Reporting 
For the purposes of this Protocol, an adverse event (AE) is defined as the appearance of 
(or worsening of any pre-existing) undesirable sign(s), symptom(s), or medical condition(s) that 
occur after a subject provides informed consent.  Abnormal laboratory values or test results 
occurring after informed consent constitute AEs only if they induce clinical signs or symptoms, 
are considered clinically meaningful, require therapy (eg, hematologic abnormality that requires 
transfusion), or require changes in the study drug(s). 
Adverse events that begin or worsen after informed consent should be recorded on the Adverse 
Events page of the CRF.  Conditions that were already present at the time of informed consent 
should be recorded on the Medical History page of the CRF.  Adverse event monitoring should 
be continued for at least 30 days after the last dose of study drug.  Adverse events (including 
laboratory abnormalities that constitute AEs) should be described using a diagnosis whenever 
possible rather than by individual underlying signs and symptoms.  When a clear diagnosis 
cannot be identified, each sign or symptom should be reported as a separate AE. 


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Adverse events will be assessed according to the CTCAE version 4.03.  The CTCAE severity 
Grade 5 (death) will not be used in this study; rather, information about deaths will be collected 
as an outcome of the event.  The occurrence of AEs should be sought by nondirective 
questioning of the subject during the screening process after signing the ICF and at each visit 
during the study.  Adverse events may also be detected when they are volunteered by the subject 
during the screening process or between visits, or through physical examination, laboratory test, 
or other assessments. 
Note that a grading scale for hyperphosphatemia (elevated serum phosphate) is not included in 
CTCAE v 4.03.  Grading should be applied using the table below and referencing the 
"investigations-other, specify" category in CTCAE v 4.03.  Hyperphosphatemia should be 
graded based on clinical severity (eg, symptoms) and medical intervention measures taken 
(eg, phosphate binders) and not on phosphate levels. 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention 
not indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
activities of daily living. 
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or 
prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
As far as possible, each AE should be evaluated to determine: 
•
The severity grade (CTCAE Grade 1 to 4).
•
Reasonable possibility that the AE is related to the study treatment:  unrelated (no) or
related (yes).
•
Start and end dates, unless unresolved at final examination.
•
Action taken with respect to study drug (eg, none, dose adjusted, temporarily
interrupted, permanently discontinued, unknown, not applicable).
•
Outcome (eg, not recovered/not resolved, recovered/resolved, recovering/resolving,
recovered/resolved with sequelae, fatal, unknown).
•
Whether it is serious, as per SAE definition provided in Section 8.3.1.
Unlike routine safety assessments, SAEs are monitored continuously and have special reporting 
requirements, see Section 8.3.2. 
All AEs should be treated appropriately.  If a concomitant medication or nondrug therapy is 
given, this action should be recorded on the AE and Prior/Concomitant medications pages of the 
CRF. 
Once an AE is detected, it should be followed until it has resolved or until it is judged to be 
permanent; assessment should be made at each visit (or more frequently if necessary) of any 
changes in severity, the suspected relationship to the study drug, the interventions required to 
treat it, and the outcome. 
Disease progression should not be regarded or reported as an AE itself, unless it is associated 
with a separate AE. 


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8.2. 
Laboratory Test Abnormalities 
8.2.1. 
Definitions and Reporting 
Laboratory abnormalities that constitute an AE in their own right (are considered clinically 
meaningful, induce clinical signs or symptoms, require concomitant therapy, or require changes 
in study drug), should be recorded on the AE page of the CRF.  Whenever possible, a diagnosis 
rather than a symptom should be provided (eg, anemia instead of low hemoglobin).  Laboratory 
abnormalities that meet the criteria for AEs should be followed until they have returned to 
normal or an adequate explanation of the abnormality is found.  When an abnormal laboratory 
test result corresponds to a sign or symptom of a previously reported AE, it is not necessary to 
separately record the laboratory test result as an additional event. 
Laboratory abnormalities that do not meet the definition of an AE should not be reported as AEs.  
A Grade 3 or 4 (severe) AE, as per CTCAE, does not automatically indicate an SAE unless it 
meets the definition of serious, as defined in Section 8.3.1, and/or per the investigator's 
discretion.  A dose interruption or adjustment for the laboratory abnormality may be required 
(see Section 5.8) and should not contribute to the designation of a laboratory test abnormality as 
an SAE. 
8.3. 
Serious Adverse Events 
8.3.1. 
Definitions 
A SAE is defined as an event that meets 1 of the following criteria: 
• Is fatal or life-threatening (ie, immediate risk of dying). 
• Results in persistent or significant disability or incapacity. 
• Constitutes a congenital anomaly or birth defect. 
• Is clinically meaningful (ie, defined as an event that jeopardizes the subject or 
requires potential medical or surgical intervention to prevent 1 of the outcomes listed 
above).  Considered meaningful by the investigator as an important medical event 
that may not result in death, be life-threatening, or require hospitalization, but may be 
considered a SAE when, based upon appropriate medical judgment, it may jeopardize 
the subject or may require medical or surgical intervention to prevent 1 of the 
outcomes listed in this definition. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is a result of: 
− Routine treatment or monitoring of the studied indication not associated with any 
deterioration in condition. 
− Elective or preplanned treatment for a pre-existing condition that is unrelated to 
the indication under study and has not worsened since signing the ICF. 
− Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 


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− Social reasons and respite care, in the absence of any deterioration in the subject's 
general condition. 
− Any SAEs that are expected due to the condition being treated, including if the 
SAE is a primary outcome measure, or where there has been a clear agreement 
with regulators not to consider these as SAEs, provided the information is 
collected elsewhere. 
8.3.2. 
Reporting 
To ensure subject safety, every SAE, regardless of suspected causality, occurring after the 
subject has signed the ICF and up to the last study visit, or up to 30 days after the subject has 
stopped study treatment, whichever is later, must be reported to the sponsor (or designee) within 
24 hours of learning of its occurrence.  Any SAEs experienced after this period should be 
reported to the sponsor (or designee) only if the investigator suspects a causal relationship to the 
study drug.  Recurrent episodes, complications, or progression of the initial SAE must be 
reported as the follow-up to the original episode within 24 hours of the investigator receiving the 
follow-up information.  An SAE occurring at a different time interval or otherwise considered 
completely unrelated to a previously reported one should be reported separately as a new event.  
Previously planned (before providing informed consent) surgeries should not be reported as 
SAEs unless the underlying medical condition worsens over the course of the study. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form.  The investigator must assess and record the relationship of each SAE to each specific 
study drug (if there is more than 1), complete the SAE Report Form in English, and send the 
completed, signed form by fax within 24 hours to the sponsor or its designee.  The investigator 
must assess if there is a reasonable possibility that the SAE is related to the study 
treatment:  unrelated (no) or related (yes). 
Serious AEs related to unblinded comparator drugs or concomitant medications/drug delivery 
systems are reported directly to the manufacturers of those drugs/devices in accordance with the 
package insert. 
The telephone and facsimile number of the sponsor's contact persons, specific to the study, are 
listed in the investigator folder provided to each site.  The original copy of the SAE Report Form 
and the fax confirmation sheet must be kept with the CRF documentation at the study site. 
Follow-up information is sent to the same person to whom the original SAE Report Form was 
sent, using a new SAE Report Form stating that this is a follow-up to the previously reported 
SAE and giving the date of the original report.  Each recurrence, complication, or progression of 
the original event should be reported as a follow-up to that event regardless of when it occurs.  
The follow-up information should describe whether the event has resolved or continues, if and 
how it was treated, and whether the subject continued or withdrew from study participation, or if 
study drug was interrupted or discontinued. 
If the SAE is not previously documented in the IB for the study drug (new occurrence) and is 
thought to be related to the sponsor's study drug, a sponsor's associate may urgently require 
further information from the investigator for reporting to health authorities. 


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The sponsor or its designee may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same drug that this SAE has been reported.  
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with 
Directive 2001/20/EC, or as per national regulatory requirements in participating countries. 
8.4. 
Emergency Unblinding of Treatment Assignment 
Not applicable. 
8.5. 
Pregnancy 
Pregnancy, in and of itself, is not regarded as an AE unless there is suspicion that study drug may 
have interfered with the effectiveness of a contraceptive medication or method.  When a 
pregnancy has been confirmed, the following procedures should occur: 
• The investigator must notify the sponsor or its designee immediately. 
• The study drug must be discontinued immediately. 
• The subject must be withdrawn from the study. 
• The EOT visit evaluations must be performed. 
• The investigator must complete and submit the Pregnancy Initial and Follow-Up 
Report forms to the sponsor or its designee. 
• A serum pregnancy test must be performed to confirm the urine pregnancy test result.  
(The serum test should be performed at the investigative site to ensure that the test 
will be performed promptly and the result available immediately for review.) 
If a negative serum test does not confirm the urine pregnancy test result, then: 
• The investigator will use his or her expert judgment, based on an assessment of the 
potential benefit/risk to the subject, to determine if it is in the subject's best interest to 
resume study drug and continue participation in the study. 
To ensure subject safety, each pregnancy in a subject during maternal or paternal 
exposures to study drug must be reported within 24 hours of learning of its occurrence.  
Data on fetal outcome and breastfeeding are collected for regulatory reporting and drug safety 
evaluation.  Follow-up to each pregnancy should be conducted to determine outcome, including 
spontaneous or voluntary termination, details of the birth, and the presence or absence of any 
birth defects, congenital abnormalities, or maternal and/or newborn complications, by following 
until the first well-baby visit.  Pregnancy should be recorded on a Clinical Study Pregnancy 
Form and reported by the investigator to the sponsor or its designee.  Pregnancy follow-up 
should be recorded on the same form and should include an assessment of the possible 
relationship to the sponsor's study drug of any pregnancy outcome and follow-up to the first 
well-baby visit.  Any SAE experienced during pregnancy must be reported on the SAE 
Report Form and to the sponsor or its designee. 


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8.6. 
Warnings and Precautions 
No evidence available at the time of the approval of this study Protocol indicated that special 
warnings or precautions were appropriate, other than those noted in the provided IB.  Additional 
safety information collected between IB updates will be communicated in the form of 
Investigator Notifications (INs).  Any important new safety information should be discussed with 
the subject during the study as needed.  If new, significant risks are identified, they will be added 
to the ICF. 
8.7. 
Data Monitoring Committee 
Not applicable. 
8.8. 
Adverse Events of Special Interest 
Not applicable. 
8.9. 
Product Complaints 
The sponsor collects product complaints on study drugs and drug delivery systems used in 
clinical studies in order to ensure the safety of study participants, monitor quality, and facilitate 
process and product improvements. 
All product complaints associated with material packaged, labeled, and released by the sponsor 
or its designee will be reported. 
The investigator or his/her designee is responsible for reporting a complete description of the 
product complaint and any associated AEs via email or other written communication to the 
Incyte contact. 
If the investigator is asked to return the product for investigation, he/she will return a copy of the 
product complaint communication with the product. 






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Table 27: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38°C 
< 35.5°C 
Respiratory rate 
> 24/min 
< 8/min 
9.4.4.4. 
Electrocardiograms 
Descriptive statistics and mean change from baseline will be determined for each ECG parameter 
at each assessment time.  Electrocardiogram results will be reviewed for clinically notable 
abnormalities according to predefined criteria (see Table 28).  Subjects exhibiting clinically 
notable ECG abnormalities will be listed.  Adverse events will be reported for clinically notable 
abnormalities that are considered clinically significant in the judgment of the investigator. 
Table 28: 
Criteria for Clinically Notable ECG Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 460 msec 
< 295 msec 
PR 
> 220 msec 
< 75 msec 
QRS 
> 120 msec 
< 50 msec 
QT 
> 500 msec 
< 300 msec 
RR 
> 1330 msec 
< 600 msec 
QTcF = Fridericia correction. 
9.4.5. 
Pharmacokinetic Analysis 
The PK parameters of Cmax, tmax, Cmin, AUC0-t, and Cl/F (INCB054828) will be calculated from 
the blood plasma concentrations of INCB054828 using standard noncompartmental 
(model-independent) PK methods.  Pharmacokinetic calculations will be performed, if 
appropriate, using commercial software such as WinNonlin® (Pharsight Corporation, Mountain 
View, CA).  Nominal times will be used in all cases, except when the difference between the 
actual time and nominal time is greater than 15 minutes for samples collected up to 4 hours after 
administration and greater than 30 minutes for samples collected more than 4 hours after 
administration; in these cases, actual time will be used for PK analysis. 
If there is a sufficient amount of plasma concentration data from this study, the data will be 
analyzed by standard population PK methods using appropriate software (eg, NONMEM). 
9.4.5.1. 
Food Effect and Renal Impairment 
The log-transformed PK parameters will be compared between the fasted and fed study drug 
administration groups in the food-effect cohort and between the renal impairment cohort and the 
normal renal function group using a 1-factor ANOVA.  The geometric mean ratio and 90% 
confidence intervals for INCB054828 Cmax, AUC0-t, and AUC0-∞ will be calculated to assess the 
magnitude of the effect of food or renal impairment on the PK of INCB054828. 


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9.5. 
Data Monitoring Committee 
Not applicable. 
9.6. 
Interim Analysis 
Not applicable. 
10. 
STUDY DRUG MATERIALS AND MANAGEMENT 
In Part 3, commercially available and commercially packaged gemcitabine, cisplatin, docetaxel, 
pembrolizumab, or trastuzumab will be utilized for this study.  See Section 10.3 for information 
on INCMGA00012. 
10.1. 
Investigational Product Description:  INCB054828 
10.1.1. 
Packaging, Labeling, and Preparation of INCB054828 
All medication labels will be in the local language and will comply with the legal requirements 
of each country. 
10.1.2. 
Formulation and Chemical Properties of INCB054828 
INCB054828 is formulated as 0.5-mg, 2.0-mg (free base equivalent), and 4.5-mg tablets.  Each 
tablet contains the active ingredient and commonly used compendial excipients such as 
microcrystalline cellulose, sodium starch glycolate, and magnesium stearate. 
10.1.3. 
Storage and Stability of INCB054828 
INCB054828 drug product should be stored at room temperature, 15°C to 30°C (59°F-86°F). 
10.2. 
Accountability, Handling, and Disposal of INCB054828 
Responsibility for drug accountability at the study site rests with the investigator; however, the 
investigator may assign some of the drug accountability duties to an appropriate pharmacist or 
other designee.  Inventory and accountability records must be maintained and readily available 
for inspection by the study monitor and are open to inspection at any time by any applicable 
regulatory authorities. 
The investigator or designee will be expected to collect and retain all used, unused, and partially 
used containers of study drug until the end of the study.  The investigator or designee must 
maintain records that document: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Subject use of the study drug including pill or unit counts from each supply 
dispensed. 
• Return of study drug to the investigator or designee by subjects. 


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These records should include dates, quantities, batch or serial numbers (if available), and the 
unique code numbers (if available) assigned to the investigational product and study subjects. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the correct 
study drug specified. 
Completed accountability records will be archived by the site.  At the completion of the study, 
the investigator or designee will oversee shipment of any remaining study drug back to the 
sponsor or its designee for destruction according to institutional standard operating procedures.  
If local procedures mandate site destruction of investigational supply, prior written approval 
must be obtained from Incyte. 
10.3. 
Investigational Product Description:  INCMGA00012 
10.3.1. 
Packaging, Labeling, and Preparation of INCMGA00012 
INCMGA00012 will be provided in a 250-mg vial.  All medication labels will be in the local 
language and will comply with the legal requirements of each country.  INCMGA00012 will be 
administered at 500 mg, diluted in 100 mL of 0.9% sodium chloride injection USP (normal 
saline), and given as an IV infusion, over 60 minutes through a filter.  Further guidance and 
information can be found in the Pharmacy Manual. 
10.3.2. 
Formulation and Chemical Properties of INCMGA00012 
INCMGA00012 drug product is provided as a sterile, preservative-free, clear to slightly 
opalescent, colorless to pale yellow or pale brown solution with a protein concentration of 
25 mg/mL.  The product is formulated in 0.95 mg/mL sodium acetate trihydrate, 0.18 mg/mL 
acetic acid, 90 mg/mL sucrose, and 0.1 mg/mL polysorbate 80 in sterile water for injection, USP, 
at a pH of 5.1. 
10.3.3. 
Storage and Stability of INCMGA00012 
INCMGA00012 drug product should be stored upright under refrigeration at 2°C to 8°C 
(36°F-46°F) and protected from light. 
10.3.4. 
Accountability, Handling, and Disposal of INCMGA00012 
Responsibility for drug accountability at the study site rests with the investigator; however, the 
investigator may assign some of the drug accountability duties to an appropriate pharmacist or 
other designee.  Inventory and accountability records must be maintained and readily available 
for inspection by the study monitor and are open to inspection at any time by any applicable 
regulatory authorities. 


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The investigator or designee will be expected to collect and retain all used, unused, and partially 
used containers of study drug until the end of the study.  The investigator or designee must 
maintain records that document the following: 
• Delivery of study drug to the study site. 
• Inventory of study drug at the site. 
• Subject use of the study drug vial counts from each supply dispensed. 
These records should include dates, quantities, batch or serial numbers (if available), and the 
unique code numbers (if available) assigned to the investigational product and study subjects. 
The investigational product must be used only in accordance with the Protocol.  The investigator 
will also maintain records adequately documenting that the subjects were provided the correct 
study drug specified. 
Completed accountability records will be archived by the site.  At the completion of the study, 
the investigator or designee will oversee shipment of any remaining study drug back to the 
sponsor or its designee for destruction according to institutional standard operating procedures.  
If local procedures mandate site destruction of investigational supply, prior written approval 
must be obtained from Incyte. 
11. 
STUDY ADMINISTRATION 
11.1. 
Data Management 
11.1.1. 
Data Collection 
The investigator will be provided with access to an electronic CRF; a set of forms will be 
completed for each subject.  Entries made in the CRF must be verifiable against source 
documents; any discrepancies should be explained and documented.  The investigator will be 
responsible for reviewing all data and CRF entries and will sign and date the designated pages in 
each subject's CRF, verifying that the information is true and correct.  The investigator is 
responsible for the review and approval of all responses. 
11.1.2. 
Data Management 
Data management will be performed from CRFs.  All CRF data are entered directly into a 
validated database by the study site.  All data entry, verification, and validation will be 
performed in accordance with the current standard operating procedures of the Data Management 
Department at the sponsor or its designee.  The database will be authorized for lock once all 
defined procedures are completed. 


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11.2. 
Study Monitoring 
Qualified representatives of the sponsor or its designee, "study monitors," will monitor the study 
according to a predetermined monitoring plan.  Monitoring visits provide the sponsor with the 
opportunity to: 
• Evaluate the progress of the study. 
• Verify the accuracy and completeness of CRFs. 
• Assure that all Protocol requirements, applicable laws and/or regulations, and 
investigator's obligations are being fulfilled. 
• Resolve any inconsistencies in the study records. 
The investigator must allow the study monitors to periodically review, at mutually convenient 
times during the study and after the study has been completed, all CRFs and office, hospital, and 
laboratory records supporting the participation of each subject in the study.  The CRFs and other 
documentation supporting the study must be kept up-to-date by the investigator and the research 
staff at the investigative site.  These study materials must be available for review by the study 
monitor, and/or other qualified representatives of the sponsor or its designee, at each monitoring 
visit. 
The study monitor will review the various records of the study (CRFs, subject medical and 
laboratory records, and other pertinent data).  The study monitor will verify the CRF data against 
original source documentation for accuracy and completeness.  The study monitor will identify 
data discrepancies and collaborate with the investigator and research staff to resolve the 
discrepancies in a timely manner.  Protocol deviations will also be identified and recorded on a 
"Protocol Deviation Log."  The study monitor will follow an "Issue Escalation" plan in order to 
ensure that each issue identified during a monitoring visit is appropriately documented, reported, 
and resolved in a timely manner in accordance with the plan's requirements. 
11.3. 
Protocol Adherence 
The principal investigator must obtain IRB or IEC approval for the investigation.  Initial IRB or 
IEC approval and all materials approved by the IRB or IEC for this study including the subject 
ICF and recruitment materials must be maintained by the investigator and made available for 
inspection. 
Each investigator must adhere to the Protocol as described in this document and agree that 
changes to the Protocol, with the exception of medical emergencies, must be discussed and 
approved, firstly, by the sponsor or its designee and, secondly, by the IRB or IEC.  Each 
investigator is responsible for enrolling subjects who have met the Protocol inclusion and 
exclusion criteria.  The IRB or IEC that granted original approval, or the IRB or IEC currently 
responsible for overseeing the conduct of the study, must be notified of all changes in and 
deviations from the Protocol that may increase risk to the subject, and/or that may adversely 
affect the rights of the subject or validity of the investigation.  The investigator must send a copy 
of the approval letter from the IRB or IEC to the sponsor or its designee and retain the original in 
the site study regulatory file. 


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Major eligibility deviations must be reported to the IRB or IEC in accordance with the IRB or 
IEC requirements.  During the course of the study, the monitor must notify the sponsor or its 
designee of subjects found not to have met eligibility criteria.  The medical monitor, in 
collaboration with the investigator, will determine if the subject should be withdrawn from the 
study. 
11.4. 
Financial Disclosure 
All clinical investigators participating in clinical studies subject to FDA Regulation Title 21 
Code of Federal Regulations (CFR) Part 54 – Financial Disclosure by Clinical Investigators, are 
required before study initiation to submit a completed Clinical Investigator Financial Disclosure 
Request Form that sufficiently details any financial interests and arrangements that apply.  For 
the purpose of this regulation, clinical investigator is defined as any investigator or 
subinvestigator who is directly involved in the treatment or evaluation of research subjects, 
including the spouse and each dependent child of the clinical investigator.  These requirements 
apply to both US and foreign clinical investigators conducting covered clinical studies. 
Any new investigators or subinvestigators added to the covered clinical study during its conduct 
must also submit a completed Clinical Investigator Financial Disclosure Request Form.  During a 
covered clinical study, any changes to the financial information previously reported by a clinical 
investigator must be reported to the sponsor or its designee.  At the conclusion of the covered 
clinical study, the clinical investigators will be reminded of their obligation to report to the 
sponsor or its designee any changes to the financial information previously reported.  The 
clinical investigators will also be reminded that they must report any changes in their financial 
information for a period of 1 year after completion of the covered clinical study. 
12. 
QUALITY CONTROL AND QUALITY ASSURANCE 
12.1. 
Sponsor Audits 
At some point during the study, individuals from the sponsor's Quality Assurance department 
and/or their authorized representative may visit the investigator's site to conduct an audit of the 
study.  The purpose of this visit will be to determine the investigator's adherence to the Protocol, 
applicable regulations, and the sponsor's procedures, in addition to assessing the accuracy of the 
study data.  Before initiating this audit, the investigator will be contacted by the sponsor to 
arrange a convenient time for this visit.  The investigator and staff are expected to cooperate with 
the auditors and allow access to all subject records supporting the CRFs and other study-related 
documents. 
12.2. 
Inspection by Regulatory Authorities 
At some point during the investigational product's development program, a regulatory authority 
may visit the investigator to conduct an inspection of the study and the site.  The investigator and 
staff are expected to cooperate with the inspectors and allow access to all source documents 
supporting the CRFs and other study-related documents.  The investigator must immediately 
notify the sponsor when contacted by any regulatory authority for purposes of conducting an 
inspection. 


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13. 
ETHICS 
13.1. 
Ethical Conduct of the Study 
This study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and conducted in adherence to the study Protocol, GCPs as defined in 
Title 21 of the US CFR Parts 50, 54 56, 312, and Part 11, as well as ICH GCP consolidated 
guidelines (E6) and applicable regulatory requirements. 
13.2. 
Written Informed Consent 
Informed consent documentation that includes both information about the study and the ICF will 
be prepared and given to the subject.  This document will contain all elements required by the 
ICH E6 Guideline for GCP and any additional elements required by local regulations.  The 
document must be in a language understandable to the subject and must specify who informed 
the subject.  Where required by local law, the person who informs the subject must be a 
physician. 
The principal investigator at each center will ensure that the subject is given full and adequate 
verbal and written information about the nature, purpose, and the possible risk and benefit of the 
study.  Subjects must also be notified that they are free to discontinue study drug and withdraw 
from the study at any time.  The subject should be given the opportunity to ask questions and 
allowed time to consider the information provided. 
The subject's signed and dated ICF must be obtained before conducting any study procedures.  
The principal investigator must maintain the original, signed ICF.  A copy of the signed ICF 
must be given to the subject.  The investigator should inform the subject's primary physician 
about the subject's participation in the study if the subject has a primary physician and if the 
subject agrees to the primary physician being informed. 
Preparation of the ICF is the responsibility of the investigator and must include all elements 
required by the ICH GCP, and applicable regulatory requirements, and must adhere to the ethical 
principles that have their origin in the Declaration of Helsinki.  A template will be provided by 
the sponsor or its designee.  The sponsor or its designee must review and approve all changes to 
site-specific ICFs.  The ICF must include a statement that the sponsor or its designee and 
regulatory authorities have direct access to subject records.  Before the beginning of the study, 
the IRB or IEC must provide the investigator with written approval/favorable opinion of the 
written ICF and any other information to be provided to the subjects. 
13.3. 
Ethics Review 
It is the responsibility of the investigator to assure that all aspects of the ethics review are 
conducted in accordance with the Declaration of Helsinki as described in the ICH E6:  Guideline 
for GCP, and/or local laws, whichever provides the greatest level of protection for the study 
participants.  The Protocol and any information supplied to the subject to obtain informed 
consent, including written ICFs, subject recruitment procedures (eg, advertisements), and written 
information to be provided to subjects (information leaflets), must be reviewed and approved by 
a qualified IRB/IEC before enrollment of participants in the study.  Before initiation of the study, 


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the sponsor or its designee must receive documentation of the IRB or IEC approval, which 
specifically identifies the study/protocol, and a list of the committee members. 
The principal investigator is responsible for informing the IRB or IEC of any amendment to the 
Protocol in accordance with local requirements.  Protocol amendments and revisions to the ICF 
must be submitted to and approved by the IRB or IEC. 
Investigators must submit progress reports to the IRB or IEC in accordance with the IRB or IEC 
requirements and local regulations.  Annual re-approval of the study must be obtained.  Copies 
of progress reports and annual re-approvals must be sent to the sponsor or its designee. 
The principal investigator is also responsible for providing the IRB or IEC with reports of any 
reportable serious adverse drug reactions from any other study conducted with the investigational 
product.  The sponsor or its designee will provide this information to the principal investigator. 
When the sponsor or its designee provides the investigator with a safety report, the investigator 
must promptly forward a copy to the IRB or IEC. 
After completion or termination of the study, the investigator must submit a final report to the 
IRB or IEC and to the sponsor or its designee. 
The investigator, as part of the records retention requirements for the study, must maintain 
documentation of all submissions, correspondence, and approvals to and from the IRB or IEC. 
Each clinical investigator is responsible to conduct the study in accordance with the Protocol, all 
applicable laws, regulations, and GCP according to ICH guidelines. 
13.4. 
Data Privacy 
The investigator and the sponsor or its designee must adhere to applicable data privacy laws and 
regulations.  The investigator and the sponsor (or its designee) are responsible for ensuring that 
sensitive information is handled in accordance with local requirements (eg, HIPAA).  
Appropriate consent and authorizations for use and disclosure and/or transfer (if applicable) of 
protected information must be obtained. 
14. 
DATA HANDLING AND RECORDKEEPING 
14.1. 
Inspection of Records 
The sponsor or its designee will be allowed to conduct site visits to the investigation facilities for 
the purpose of monitoring any aspect of the study.  The investigator agrees to allow the monitor 
to inspect the drug storage area, study drug stocks, drug accountability records, subject charts 
and study source documents, and other records relative to study conduct. 
The investigator must ensure that all records pertaining to the conduct of the clinical study 
(as listed above) are adequately maintained for a period of 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated marketing 
applications in an ICH region, or at least 2 years have elapsed since the formal termination of 
clinical development of the investigational product. 


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14.2. 
Retention of Records 
The principal investigator must maintain all documentation relating to the study for a period of 
2 years after the last marketing application approval, or if not approved, 2 years following the 
termination of the test article for investigation.  If it becomes necessary for the sponsor or the 
regulatory authority to review any documentation relating to the study, the investigator must 
permit access to such records. 
The investigator must not destroy any records associated with the study without receiving 
approval from Incyte.  The investigator must notify the sponsor or its designee in the event of 
accidental loss or destruction of any study records.  If the investigator leaves the institution 
where the study was conducted, the sponsor or its designee must be contacted to arrange 
alternative record storage options. 
Whenever possible, an original recording of an observation must be retained as the source 
document.  However, a photocopy of a record is acceptable, provided it is legible and is a 
verified copy of the original document. 
All CRF data entered by the site (including audit trail), as well as computer hardware and 
software (for accessing the data), will be maintained or made available at the site in compliance 
with applicable record retention regulations.  The sponsor will retain the original CRF data and 
audit trail. 
14.3. 
Confidentiality 
Subject names will not be supplied to the sponsor or its designee if applicable.  Only the subject 
number and subject's initials will be recorded in the CRF, where permitted; if the subject's name 
appears on any other document (eg, laboratory report), it must be obliterated on the copy of the 
document to be supplied to the sponsor or its designee.  Study findings stored on a computer will 
be stored in accordance with local data protection laws.  The subjects will be informed that 
representatives of the sponsor or its designee, IRB or IEC, or regulatory authorities may inspect 
their medical records to verify the information collected, and that all personal information made 
available for inspection will be handled in strictest confidence and in accordance with local data 
protection laws. 
15. 
PUBLICATION POLICY 
By signing the study Protocol, the investigator and his or her institution agree that the results of 
the study may be used by the sponsor, Incyte Corporation (Incyte), for the purposes of national 
and international registration, publication, and information for medical and pharmaceutical 
professionals.  If necessary, the authorities will be notified of the investigator's name, address, 
qualifications, and extent of involvement.  The terms regarding the publication of study results 
are contained in the agreement signed with the sponsor or its designee.  The signed agreement is 
retained by the sponsor or its designee. 


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16. 
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Docetaxel [USPI]. Lake Forest, IL: Hospira, Inc.; 2014. 
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Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple 
myeloma. Leukemia 2006;20:1467-1473. 
Dutt A, Salvesen HB, Chen TH, et al. Drug-sensitive FGFR2 mutations in endometrial 
carcinoma. Proc Natl Acad Sci U S A 2008;105:8713-8717. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-224. 
Elbauomy Elsheikh S, Green AR, Lambros MB, et al. FGFR1 amplification in breast 
carcinomas: a chromogenic in situ hybridisation analysis. Breast Cancer Res 2007;9:R23. 
Eswarakumar VP, Lax I, Schlessinger J. Cellular signaling by fibroblast growth factor receptors. 
Cytokine Growth Factor Rev 2005;16:139-149. 
Farrow EG, White KE. Recent advances in renal phosphate handling. Nat Rev Nephrol 
2010;6:207-217. 
FDA. Pharmacology Review; BLA No. 125514 for KEYTRUDA (pembrolizumab). FDA CDER 
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FDA. Pharmacology Review; BLA No. 125554 for OPDIVO (nivolumab). FDA CDER 2014 
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Liao RG, Jung J, Tchaicha J, et al. Inhibitor-sensitive FGFR2 and FGFR3 mutations in lung 
squamous cell carcinoma. Cancer Res 2013;73:5195-5205. 
Mehnert J, Joshua A, Lakhani N, et al. First-in-human Phase 1 study of INCMGA00012 in 
patients with advanced solid tumors: interim results of the cohort expansion phase. Abstract 
P669 presented at: The Society for Immunotherapy of Cancer; November 7-11, 2018; 
Washington, DC. 
National Cancer Institute (NCI). Common Terminology Criteria for Adverse Events (CTCAE) 
Version 4.03. 2010. http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-
14_QuickReference_5x7.pdf. Accessed October 14, 2014. 
Oken MM, Creech RH, Tormey DC, et al. Toxicity and response criteria of the Eastern 
Cooperative Oncology Group. Am J Clin Oncol 1982;5:649-655. 
Pai R, French D, Ma N, et al. Antibody-mediated inhibition of fibroblast growth factor 19 results 
in increased bile acids synthesis and ileal malabsorption of bile acids in cynomolgus monkeys. 
Toxicol Sci 2012;126:446-456. 
Paik P, Shen R, Ferry D, et al. A Phase 1b open-label multicenter study of AZD4547 in patients 
with advanced squamous cell lung cancers: preliminary antitumor activity and 
pharmacodynamics data. J Clin Oncol 2014;32:5s abstract 8035. 
Pardo OE, Arcaro A, Salerno G, Raguz S, Downward J, Seckl MJ. Fibroblast growth factor-2 
induces translational regulation of Bcl-XL and Bcl-2 via a MEK-dependent pathway: correlation 
with resistance to etoposide-induced apoptosis. J Biol Chem 2002;277:12040-12046. 
Pembrolizumab [USPI]. Whithouse Station, NJ: Merck Sharp & Dohme Corp; 2016. 
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71b91a02b287. Accessed August 25, 2016. 
Pembrolizumab [SmPC]. Hoddesdon, UK: Merck Sharp & Dohme Limited; 2015. 
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t(4;14)-positive multiple myeloma in mice. J Clin Invest 2009;119:1216-1229. 
Quezada SA, Peggs KS. Exploiting CTLA-4, PD-1 and PD-L1 to reactivate the host immune 
response against cancer. Br J Cancer 2013;108:1560-1565. 
Rades D, Setter C, Dahl O, Schild SE, Noack F. Fibroblast growth factor 2--a predictor of 
outcome for patients irradiated for stage II-III non-small-cell lung cancer. Int J Radiat Oncol Biol 
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Robert C, Ribas A, Wolchok JD, et al. Anti-programmed-death-receptor-1 treatment with 
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Sequist L, Cassier P, Varga A, et al. Phase I study of BGJ398, a selective pan-FGFR inhibitor in 
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APPENDIX A. INFORMATION REGARDING EFFECTIVENESS OF 
CONTRACEPTIVE METHODS 
For Subjects Participating in the Study: 
The following methods that can achieve a failure rate of less than 1% per year when used 
consistently and correctly are considered as highly effective birth control methods.  
Such methods include: 
• Combined (estrogen and progestogen containing) hormonal contraception associated 
with inhibition of ovulation1 
− oral 
− intravaginal 
− transdermal 
• Progestogen-only hormonal contraception associated with inhibition of ovulation1 
− oral 
− injectable 
− implantable2 
• Intrauterine device (IUD)2 
• Intrauterine hormone-releasing system (IUS)2 
• Bilateral tubal occlusion2 
• Vasectomised partner2,3 
• Sexual abstinence4 
 
1  Hormonal contraception may be susceptible to interaction with the IMP, which may reduce the efficacy of the 
contraception method. 
2  Contraception methods that in the context of this guidance are considered to have low user dependency. 
3  Vasectomised partner is a highly effective method provided of avoiding pregnancy that partner is the sole sexual 
partner of the WOCBP trial participant and that the vasectomised partner has received medical assessment of the 
surgical success.  
4  In the context of this guidance, sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study treatments.  The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the 
preferred and usual lifestyle of the subject. 
Source: CTFG 2014. 


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APPENDIX B. PHARMACOKINETIC ANALYTICAL PARAMETERS 
Cave 
Average steady-state plasma concentration (AUC0-12h/12h or 
AUC0-24h/24h) 
Cmax 
Maximum observed plasma concentration 
Cmin 
Minimum observed plasma concentration during the dosing interval 
Tmax 
Time to maximum plasma concentration 
AUC0-t 
Area under the single-dose plasma concentration-time curve from Hour 0 
to the last quantifiable measurable plasma concentration, calculated by the 
linear trapezoidal rule for increasing concentrations and the log 
trapezoidal rule for decreasing concentrations 
AUC0-τ (ie, 
AUC0-12h or 
AUC0-24h) 
Area under the steady-state plasma concentration-time curve over 
1 dosing interval (ie, from Hour 0 to 12 for BID administration or from 
Hour 0 to 24 for QD administration), calculated by the linear trapezoidal 
rule for increasing concentrations and the log trapezoidal rule for 
decreasing concentrations 
λz 
Apparent terminal phase disposition rate constant, where λz is the 
magnitude of the slope of the linear regression of the log concentration 
versus time profile during the terminal phase 
t½ 
Apparent plasma terminal phase disposition half-life (whenever possible), 
where t½ = (ln2) / λz 
Cl/F 
Oral dose clearance 
Vz/F 
Apparent oral dose volume of distribution 
Fluctuation 
Steady-state fluctuation ([Cmax – Cmin]/Cave) 
In addition, the following PK parameters may be calculated, whenever possible, for each subject 
based on the urine INCB054828 concentrations: 
Ae 
Amount of drug excreted in the urine over sampling interval 
CLR 
Renal clearance, where CLR = Ae/AUC 
% Excreted or fe 
percent excreted in the urine, where % Excreted = 100 (Ae/dose) 
Pharmacokinetic calculations will be performed, if appropriate, using commercial software such 
as WinNonlin® (Pharsight Corporation, Mountain View, CA).  Additional details of analyses will 
be described in the data analysis plan. 


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APPENDIX C. EASTERN COOPERATIVE ONCOLOGY GROUP 
PERFORMANCE STATUS 
Grade 
Performance Status 
0 
Fully active, able to carry on all predisease performance without restriction. 
1 
Restricted in physically strenuous activity but ambulatory and able to carry out work of a light 
or sedentary nature, eg, light house work, office work. 
2 
Ambulatory and capable of all selfcare but unable to carry out any work activities.  Up and 
about more than 50% of waking hours. 
3 
Capable of only limited self-care, confined to bed or chair more than 50% of waking hours. 
4 
Completely disabled.  Cannot carry on any self-care.  Totally confined to bed or chair. 
5 
Dead. 
Source:  Oken et al 1982. 


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APPENDIX D. RESPONSE ASSESSMENT CRITERIA FOR MULTIPLE 
MYELOMA 
 


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Source:  Durie et al 2006. 


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APPENDIX E. RESPONSE ASSESSMENT CRITERIA FOR SUBJECTS 
WITH MYELOPROLIFERATIVE NEOPLASMS  
Response Criteria for Myeloproliferative Neoplasms With Genetic Alterations in FGF or 
FGFR Gene 
Complete Response 
Criteria 
Hematologic 
Durable peripheral blood count remission, defined as:  absence of circulating blasts, 
hemoglobin ≥ 100 g/L and < ULN, platelet count ≥ 100 × 109/L and < ULN, WBC and 
neutrophil count within institutional normal range. 
For subjects with baseline eosinophilia:  eosinophils < 1.5 × 109/L. 
Bone marrow 
Cellularity appropriate for age, resolution of abnormal morphology, blasts ≤ 5%. 
Spleen 
For subjects with splenomegaly at baseline:  < 25% increase in spleen size by palpation 
or imaging if baseline spleen is < 10 cm or < 50% if baseline spleen is ≥ 10 cm. 
Lymph nodes 
For subjects with lymph node disease:  target nodes/nodal masses must regress to 
≤ 1.5 cm in longest transverse diameter of lesion, no extralymphatic sites of disease, no 
new lesions present.  Must be PET negative, if positive at baseline. 
Cytogenetic CR 
Meets above criteria and MPN-associated cytogenetic abnormalities are no longer 
detected (requires that abnormalities were found at baseline). 
Molecular CR 
Meets above criteria and MPN-associated molecular abnormalities (eg, by PCR) are no 
longer detected (requires that abnormalities were found at baseline) 
Partial Response  
 
Hematologic 
Hemoglobin ≥ 100 g/L and < ULN, 50% reduction in WBC and neutrophil count, 
50% reduction in circulating blasts.  
For subjects with eosinophilia:  > 50% reduction in eosinophil count. 
Bone marrow 
> 50% reduction in blasts. 
Spleen 
For subjects with splenomegaly:  < 25% increase in spleen size by palpation or imaging if 
baseline spleen is < 10 cm or < 50% if baseline spleen is ≥ 10 cm. 
Lymph nodes 
For subjects with lymph node disease:  ≥ 50% decrease in the sum of the product of the 
perpendicular diameters of up to 6 target measureable nodes and extranodal sites, no new 
lesions present. 
Cytogenetics 
No new abnormalities detected. 
Molecular markers 
No new abnormalities detected. 
Stable Disease 
 
 
Failure to achieve at least Partial Remission, but no evidence of progression for at least 
9 weeks. 
Progressive Disease 
 
Hematologic  
WBC:  > 2 times increase compared with baseline count in the absence of a concurrent 
acute or subacute medical illness. 
For subjects with circulating blasts:  ≥ 50% increase in circulating blasts. 
Bone marrow 
≥ 50% increase in blasts. 
Spleen 
For subjects with splenomegaly:  > 25% increase in spleen size by palpation or imaging if 
baseline spleen is < 10 cm and > 50% if baseline spleen is ≥ 10 cm or appearance of new 
splenomegaly. 
Lymph nodes 
If lymph node disease is present:  a single node must be abnormal with the longest 
transverse diameter > 1.5 cm and  ≥ 50% increase in the sum of measureable lesions or 
new or clear progression of pre-existing nonmeasured lesions. 
CR = complete response; MPN = myeloproliferative neoplasm; PCR = polymerase chain reaction; PET = positron emission 
tomography; ULN = upper limit of normal; WBC = white blood cell. 


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APPENDIX F. PROTOCOL AMENDMENT SUMMARY OF CHANGES 
Document 
Date 
Amendment (Version) 1: 
19 NOV 2014 
Amendment (Version) 2: 
11 JUN 2015 
Amendment (Version) 3: 
02 NOV 2015 
Amendment (Version) 4: 
09 MAR 2016 
Amendment (Version) 5: 
27 SEP 2016 
Amendment (Version) 6: 
26 JUN 2017 
Amendment (Version) 7: 
10 AUG 2018 
Amendment (Version) 8: 
11 DEC 2018 
Amendment (Version) 9: 
02 JUL 2019 
Amendment (Version) 10: 
27 MAR 2020 
Amendment 10 (27 MAR 2020) 
Overall Rationale for the Amendment:  To incorporate administrative changes and include 
updated language for comprehensive eye examination, per FDA feedback. 
1. Section 5.8.2, Criteria and Procedures for Interruption of INCB054828  
Description of change:  Added guidance for dose reduction and for . treatment 
associated with SRD/RPED. 
Rationale for change:  To provide specific guidance. 
2. Section 5.8.4, Criteria for Permanent Discontinuation of INCB054828 
Description of change:  Dose reduction language was revised. 
Rationale for change:  For clarification. 
3. Section 5.8.3, Management of Hyperphosphatemia  
Description of change:  Updated to include information on diet modification and 
phosphate binders. 
Rationale for change:  To provide more specific guidance on the management of 
hyperphosphatemia. 
4. Section 6, Study Assessments (Table 19: Schedule of Assessments); Section 7.4.7, 
Comprehensive Eye Examination 
Description of change:  Language added to include  optic coherence tomography as part 
of the regularly scheduled eye examinations. 
Rationale for change:  Per FDA requirement. 
5. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 9 (02 JUL 2019) 
Overall Rationale for the Amendment:  To add a BID dosing regimen and update the clinical 
experience section. 
1. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Added language to hemoglobin exclusion criteria regarding 
transfusion allowance with appropriate washout before enrollment. 
Rationale for change:  To allow transfusions to elevate low hemoglobin but requiring 
washout to ensure durable hemoglobin levels and not transient following transfusion. 
2. Synopsis; Section 4.1, Overall Study Design; Section 9.2, Selection of Sample Size 
Description of change:  Updated the number of subjects per study. 
Rationale for change:  Added another cohort to Part 1 and Part 2. 
3. Synopsis; Section 1.5,  Justification of Route, Dose Regimen, and Treatment Period; 
Section 3.1, Subject Inclusion Criteria; Section 4.1, Overall Study Design (including 
Figure 3: Study Design); Section 5.1.1, Treatment Regimen for INCB054828; 
Section 6, Study Assessments (Table 20: Laboratory Assessments); Section 7.7, 
Pharmacokinetic Assessments (including Table 25: Pharmacokinetic Blood 
Sampling [Part 2]) 
Description of change:  Added BID dosing regimen for INCB054828 and amended the 
PK assessment schedule for BID dosing. 
Rationale for change:  To Increase dose exposure with BID dosing. 
4. Section 1.4.2, Potential Risks of INCB054828 Based on Clinical Experience 
Description of change:  Updated the clinical experience section. 
Rationale for change:  To provide updated information from the current IB. 
5. Section 5.8.2, Criteria and Procedures for Interruption of INCB054828 
Description of change:  Added recommendation to discuss suspected or documented 
serous retinal detachment with the medical monitor before modifying the INCB054828 
dose. 
Rationale for change:  To allow conversation with an Incyte representative before 
treatment is modified. 
6. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 8 (11 DEC 2018) 
Overall Rationale for the Amendment: 
Changes were made to the Protocol based on FDA feedback after review of Amendment 7.  
Additional changes include the modification of ECG sampling times and the addition of a 
4.5-mg tablet across all sites/countries. 
1. Synopsis; Section 1.5.1, INCB054828; Section 4.1.2, Part 2 Dose Expansion; 
Section 4.4, Number of Subjects; Section 9.2, Selection of Sample Size 
Description of change:  The number of subjects in Part 2 and the total sample size have 
been increased. 
Rationale for change:  Additional treatment groups have been added. 
2. Synopsis; Section 3.1, Subject Inclusion Criteria; Section 3.2, Subject Exclusion 
Criteria 
Description of change:  Inclusion criterion 8 and exclusion criterion 19 have been 
revised to indicate that subjects enrolled in Part 3 combination with INCMGA00012 
should avoid pregnancy or fathering a child through 6 months after the last dose of 
INCMGA00012.  Exclusion criterion 9 has been revised to indicate the minimum 
washout period for subjects enrolled in Part 3 (pembrolizumab or INCMGA00012). 
Rationale for change:  Additional time is needed for contraception for subjects receiving 
INCMGA00012 and pembrolizumab due to the half-life of the product. 
3. Synopsis; Section 3.2, Subject Exclusion Criteria; Section 5.12, Prohibited 
Medications and Measures 
Description of change:  Language has been added to indicate that the use of live 
vaccines is prohibited for subjects receiving pembrolizumab or INCMGA00012. 
Rationale for change:  The restriction is standard for immune-modulating drugs. 
4. Synopsis; Section 5.1.1, Treatment Regimen for INCB054828; Section 7.9.1, 
Administration of INCB054828 
Description of change:  Language has been added regarding the administration of 
INCB054828 regardless of food. 
Rationale for change:  The food effect study has shown no impact of food on 
INCB054828; therefore, restrictions have been lifted. 
5. Synopsis; Section 10.1.2, Formulation and Chemical Properties of INCB054828 
Description of change:  The specification that the 4.5-mg tablet will be for Denmark 
only has been removed. 
Rationale for change:  The 4.5-mg tablet will be available in all regions of the study. 


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6. Section 1.3.3, INCMGA00012 
Description of change:  Updated safety data from study INCMGA 0012-102 were 
added. 
Rationale for change:  New information for INCMGA00012 is available. 
7. Section 1.4.7, Potential Risks of INCMGA00012 
Description of change:  Language has been added to specify potentially serious irAEs 
and other reactions. 
Rationale for change:  Updated information from the INCMGA00012 program is 
available. 
8. Section 3.2, Subject Exclusion Criteria; Section 5.11, Restricted Medications and 
Measures; Section 5.12, Prohibited Medications and Measures 
Description of change:  Language has been modified to allow or restrict different 
medications. 
Rationale for change:  Based on recent information, the use proton pump inhibitors is 
unrestricted and administration of moderate CYP inducers is prohibited. 
9. Section 5.1.2, Treatment Regimen for Gemcitabine + Cisplatin (Part 3 Only); 
Section 5.1.3, Treatment Regimen for Docetaxel (Part 3 Only); Section 5.1.4, 
Treatment Regimen for Pembrolizumab (Part 3 Only); Section 5.1.5, Treatment 
Regimen for Trastuzumab (Part 3 Only) 
Description of change:  Language has been added for dosing delays and restarting of 
drug. 
Rationale for change:  Based on FDA feedback after review of Amendment 7. 
10. Section 5.6, Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose 
for INCB054828 (Table 6:  Definition of Dose-Limiting Toxicity and Maximum 
Tolerated Dose of INCB054828) 
Description of change:  The reference to INCMGS00012 and immune-related toxicity 
has been deleted and Hy's Law criteria have been added. 
Rationale for change:  The FDA provided feedback to add Hy's Law criteria.  
INCMGA00012 and immune-related toxicity were deleted because they are not 
applicable to INCB054828. 
11. Section 5.8.1, Planned Dose Modifications for INCB054828 
Description of change:  The criteria were updated to provide instructions for 
up-titration. 
Rationale for change:  To allow up-titration for subjects without hyperphosphatemia 
due to possible low drug exposure. 


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12. Section 5.8.5, Dose Modifications and Management of Adverse Events Associated 
with Gemcitabine + Cisplatin, Docetaxel, Pembrolizumab, Trastuzumab; 
Section 5.8.6, Planned Dose Modification and Management of Adverse Events for 
INCMGA00012 (including Table 9 through Table 18); Section 5.8.7, Permanent 
Discontinuation of INCMGA00012 Due to Toxicity 
Description of change: Language regarding toxicity management has been modified. 
Rationale for change:  The language has been updated based on FDA feedback on 
INCB 54828-101 Protocol Amendment 7 and changes to INCMGA00012 Protocols. 
13. Section 6, Study Assessments (Table 19:  Schedule of Assessments); Section 7.4.5, 
Twelve-Lead Electrocardiograms (including Table 23:  Electrocardiogram Timed 
Measurements) 
Description of change:  The testing schedule for ECGs has been modified. 
Rationale for change:  To pair ECG testing with PK draws. 
14. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 7 (10 AUG 2018) 
Overall Rationale for the Amendment: 
The Protocol has been updated to include 1) a new combination treatment arm, 2) a renally 
impaired treatment arm, and 3) mandatory biopsies.  Additional revisions are noted below. 
1. Synopsis; Section 1.3.1, Rationale for Evaluating Safety and Pharmacokinetics in 
Subjects With Renal Impairment; 
 Section 3.1, 
Subject Inclusion Criteria; Section 3.2, Subject Exclusion Criteria; Section 4.1, 
Overall Study Design; Section 4.1.1, Part 1 Dose Escalation; 
 
 Section 6, Study Assessments (Table 20:  Laboratory 
Assessments); Section 7.7.3, Renal Impairment Cohort; Section 9.4.5.1, Food Effect 
and Renal Impairment 
Description of change:  Language has been added to include in Part 1 a subset of 
subjects with moderate and severe renal impairment.  Pharmacokinetic assessments will 
be conducted on these subjects and overall analysis of the data will be done. 
Rationale for change:  The change allows for the inclusion of renally impaired subjects 
for treatment and analysis in this study. 
2. Synopsis; Section 4.1, Overall Study Design; Section 4.1.2, Part 2 Dose Expansion; 
Section 6, Study Assessments (Table 20:  Laboratory Assessments); Section 7.8.4, 
Tumor Biopsy 
Description of change:  Language has been added to indicate that all subjects entered 
into the tumor-specific cohorts in Part 2 and Part 3 must undergo mandatory biopsies. 
Rationale for change:  To adjust the mandatory biopsy requirement for any subject 
enrolled in the tumor-specific cohort. 
3. Synopsis; Section 1, Introduction; Section 3, Subject Eligibility; Section 4.1, Overall 
Study Design; Section 4.1.3, Part 3 Combination Dose Finding and Expansion; 
Section 5, Treatment of Subjects; Section 6, Study Assessments (Table 19:  Schedule 
of Assessments); Section 10.3, Investigational Product Description:  INCMGA00012 
Description of change:  Sections and corresponding tables and figures have been added 
or updated to include a new combination therapy (INCMGA00012) to Part 3 of this 
study. 
Rationale for change:  A new combination therapy (INCMGA00012) has been added to 
Part 3 of this study. 
4. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Language for several of the exclusion criteria have been 
modified. 
Rationale for change:  To update the inclusion and exclusion criteria to match recent 
clinical experience or updated preclinical experience or new guidance in industry 
(ie, ASCO). 


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5. Synopsis; Section 4.4, Number of Subjects; Section 9.2, Selection of Sample Size 
Description of change:  Total sample size has been increased. 
Rationale for change:  Total sample size was increased due to changes in cohort sizes. 
6. Section 1.2.2, Nonclinical Drug Metabolism and Pharmacokinetics of INCB054828; 
Section 1.4.2.1, Pharmacokinetic/Pharmacodynamic Summary 
Description of change:  Revised with updated data. 
Rationale for change:  To provide updated PK data. 
7. Section 1.4.2, Potential Risks of INCB054828 Based on Preliminary Clinical 
Experience 
Description of change:  Revised with updated clinical data. 
Rationale for change:  To provide updated risk language based on new clinical data. 
8. Section 4.1.2, Part 2 Dose Expansion 
Description of change:  Adding a specific cholangiocarcinoma with FGFR2 
translocation cohort with required biopsies. 
Rationale for change:  To enroll subjects in a target population in order to obtain tissue 
samples for analysis. 
9. Section 6, Study Assessments (Table 19:  Schedule of Assessments); Section 7.4.5, 
Twelve-Lead Electrocardiograms 
Description of change:  Updated postdose ECG times to include 4 hours and added 
timing details to Table 19. 
Rationale for change:  Clarification. 
10. Section 6, Study Assessments (Table 19:  Schedule of Assessments); Section 7.4.7, 
Comprehensive Eye Examination 
Description of change:  Language has been added to list additional required assessments 
and optical coherence tomography for clinical symptoms. 
Rationale for change:  Based on clinical data generated to date, the need for more 
comprehensive eye toxicity monitoring is required. 
11. Section 
 
Description of change:  Language has been added to specify analyses to be completed 
on samples. 
Rationale for change:  To provide a comprehensive list of analyses on samples 
collected. 


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12. Section 8.1.1 Definitions and Reporting 
Description of change:  Language has been added to specify how hyperphosphatemia 
should be reported. 
Rationale for change:  The current CTCAE v 4.03 does not list hyperphosphatemia; 
therefore, guidance has been added to the Protocol for hyperphosphatemia since it is an 
on-target event. 
13. Appendix F, Inhibitors of CYP3A; Appendix G, Inducers of CYP3A 
Description of change:  These appendices have been deleted. 
Rationale for change:  These lists will no longer be provided as part of the Protocol. 
14. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 6 (26 JUN 2017) 
The primary purpose of this amendment is to increase the number of subjects in Part 2 and make 
changes to clarify and/or simplify the current study design.  
1. Synopsis; Section 1.5.1, INCB054828; Section 3.1, Subject Inclusion Criteria; 
Section 4.1, Overall Study Design (including Figure 1, Study Design); Section 4.1.2, 
Part 2 Dose Expansion; Section 4.4, Number of Subjects; Section 9.2, Selection of 
Sample Size 
Description of change:  Part 2 was revised to include approximately 15 subjects with 
specific tumor types (5 bladder cancer, 5 lung cancer, and 5 HPV-positive with 
FGFR-alteration tumors); approximately 6 of these subjects (2 per tumor type) will have 
mandatory biopsies.  The number of subjects was updated accordingly. 
Rationale for change:  Additional on-treatment tissue required to assess impact of 
INCB054828 on specific tumor types. 
2. Synopsis; Section 4.1.1, Part 1 Dose Escalation; Section 5.1.1, Treatment Regimen 
for INCB054828; Section 7.9.1, Administration of INCB054828 
Description of change:  Updated to reflect that a continuous study drug administration 
regimen will be explored and added language to explain required dosing completion for 
an evaluable subject and how INCB054828 should be administered in that regimen. 
Rationale for change:  To clarify evaluability of subjects receiving the continuous study 
drug administration regimen. 
3. Synopsis; Section 4.1.1.3, Lower Dose Level Expansion; Section 4.1.2, Part 2 Dose 
Expansion; Section 4.1.3, Part 3 Combination Dose Finding and Expansion; 
Section 7.8.4, Tumor Biopsy 
Description of change:  Added language to specify requirements for mandatory biopsy 
tissue collection. 
Rationale for change:  To simplify the process and provide clarity to timepoints. 
4. Section 1.4.2, Potential Risks of INCB054828 Based on Preliminary Clinical 
Experience 
Description of change:  Updated section with more recent clinical experience data. 
Rationale for change:  Updated to match the Investigator's Brochure. 
5. Synopsis; Section 3.2, Subject Exclusion Criteria 
Description of change:  Adjustment was made to criterion regarding previous receipt of 
anticancer medication to 28 days (criterion 1).  Added language to adjust serum 
phosphorus and parathyroid hormone requirements (criterion 3).  Added language for 
ectopic mineralization/calcification to exclude certain circumstances that do not apply to 
this criterion (criterion 6).  A new criterion was added to exclude previous anti-PD1 
therapy in subjects in the Part 3 pembrolizumab group (criterion 24). 


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Rationale for change:  To minimize the window of previous exposure to anticancer 
medications and to adjust the exclusion criterion for laboratory parameters and ectopic 
mineralization/calcification.  New criterion was added to exclude previous exposure to 
anti-PD1 treatments. 
6. Synopsis; Section 6.1, Screening Phase 
Description of change:  Added language to allow prescreening for subjects without 
genomic testing results (Part 2 and Part 3). 
Rationale for change:  Subjects in Part 2 and Part 3 require documentation of genomic 
sequencing results.  Subjects who do not have this may be sequenced prior to signing the 
study informed consent and are subjected to the 28-day screening window. 
7. Section 5.1.2, Treatment Regimen for Gemcitabine + Cisplatin (Part 3 Only); 
Section 5.1.3, Treatment Regimen for Docetaxel (Part 3 Only); Section 5.1.4, 
Treatment Regimen for Pembrolizumab (Part 3 Only); Section 5.1.5, Treatment 
Regimen for Trastuzumab (Part 3 Only)  
Description of change:  Added language to allow discontinuation of 
chemotherapy/immunotherapy. 
Rationale for change:  Chemotherapy/immunotherapy may be administered for a finite 
period of time, but INCB054828 may be given indefinitely.  The added language allows 
investigators to stop chemotherapy/immunotherapy based on their discretion. 
8. Section 3.1, Study Population 
Description of change:  Section 3.1 was deleted. 
Rationale for change:  Section was redundant with the inclusion/exclusion criteria 
sections. 
9. Section 5.7.3, Management of Hyperphosphatemia (Table 6, Recommended 
Approach for Hyperphosphatemia Management) 
Description of change:  Added language specifically for subjects in the continuous study 
drug administration cohorts. 
Rationale for change:  Subjects in the continuous study drug administration cohorts do 
not have planned dose holds; therefore, the language needed to include statements for 
interruption and reductions for this group of subjects. 
10. Section 5.8, Withdrawal of Subjects From Study Treatment 
Description of change:  Added language to provide more clarity. 
Rationale for change:  To provide more clarity on the withdrawal process and 
follow-up. 
11. Section 5.10, Restricted Medications and Measures; Section 5.11, Prohibited 
Medications and Measures 
Description of change:  Moved calcium-based binders from Section 5.11 to Section 5.10 
and added aluminum-based phosphate binders to Section 5.10. 




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Amendment 5 (27 SEP 2016) 
The primary purpose of this amendment is to revise the study design in order to add a continuous 
dosing cohort, a trastuzumab combination cohort in Part 3, and a lower dose level cohort in 
Part 1 and Part 3 with mandatory biopsies, and to increase the number of subjects in this study. 
1. Synopsis; Section 1.5.2, Rationale for Continuous Administration of INCB054828; 
Section 4.1, Overall Study Design; Section 4.1.1.3, Lower Dose Level Expansion; 
Section 4.1.3, Part 3 Combination Dose Finding and Expansion; Section 4.4, 
Number of Subjects; Section 5.1.1, Treatment Regimen for INCB054828; Section 6, 
Study Assessments (Table 7); Section 7.8.4, Tumor Biopsy 
Description of change:  A continuous study drug administration regimen has been 
added to Part 1.  Lower dose level cohorts have been added to Part 1 and Part 3, with 
paired biopsies required.  The number of subjects in Part 1 and Part 3 have been 
increased. 
Rationale for change:  The continuous administration regimen is being added to allow 
for an additional dose regimen option.  The lower dose level cohorts were added to 
obtain more data at the dose level below the RP2D and allow paired biopsies to be 
collected. 
2. Synopsis; Section 1.3.1, Rationale for Combining INCB054828 with Chemotherapy, 
Programmed Cell Death-1 Inhibitor and Trastuzumab; Section 1.4.6, Potential 
Risks of Trastuzumab; Section 1.4.7, Potential Risks Related to the Combination 
Regimens; Section 1.5.6, Trastuzumab; Section 3, Subject Eligibility; Section 4.4, 
Number of Subjects; Section 5.1.5, Treatment Regimen for Trastuzumab (Part 3 
Only); Section 5.7.5, Management of Adverse Events Associated with Gemcitabine 
+ Cisplatin, Docetaxel, Pembrolizumab, or Trastuzumab; Section 6, Study 
Assessments (Table 7); Section 7.4.6, Echocardiogram/Multigated Acquisition 
Scan; Section 10, Study Drug Materials and Management 
Description of change:  A trastuzumab combination cohort was added to Part 3.  
Relevant sections have been updated accordingly, including background information and 
dose regimen for trastuzumab (Part 3 only).  An exclusion criterion was added for 
subjects being considered for treatment in the trastuzumab combination arm (left 
ventricular ejection fraction < 50% on echocardiogram or MUGA scan). 
Rationale for change:  A trastuzumab combination cohort was added for exploration of 
an additional combination therapy, and relevant sections were updated accordingly.  
Exclusion criterion added per labeled criterion for subjects receiving trastuzumab. 
3. Synopsis; Section 3.1, Study Population; Section 4.1, Overall Study Design  
Description of change:  Specific tumor types for Part 2 have been deleted and the 
inclusion criterion outlining the different tumor types allowed in Part 2 have been 
removed. 
Rationale for change:  All subjects with a documented FGF/FGFR alteration will be 
allowed to enroll. 


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4. Synopsis; Section 3.3, Exclusion Criteria; Section 6, Study Assessments (Table 11)  
Description of change:  Separated the HIV and hepatitis language into 2 criteria; 
revised language for hepatitis. 
Rationale for change:  Revision of HIV and hepatitis language to be clearer for 
selection of subjects. 
5. Synopsis; Section 9.2, Selection of Sample Size 
Description of change:  The effect size of this section was changed to account for the 
increase in number of subjects in each part. 
Rationale for change:  The number of subjects in Part 3 has increased.  Additionally, 
the tumor type "buckets" have been removed from Part 2. 
6. Section 1.4.2, Potential Risks of INCB054828 Based on Preliminary Clinical 
Experience 
Description of change:  Updated with clinical data as of 09 AUG 2016. 
Rationale for changes:  To provide investigators with current information. 
7. Section 1.5.3, Gemcitabine + Cisplatin; Section 5.1.2, Treatment Regimen for 
Gemcitabine + Cisplatin (Part 3 Only); Section 6, Study Assessments (Table 7) 
Description of change:  Gemcitabine dose regimen has been changed to administration 
on Days 1 and 8 only. 
Rationale for change:  The gemcitabine regimen is based on a 28-day cycle.  
INCB054828 is a 21-day cycle.  The additional dose on Day 15 did not allow subjects to 
have enough of a break in between cycles. 
8. Section 5.7.2, Criteria and Procedures for Interruption of INCB054828 (Table 5) 
Description of change:  In Table 5 (Guidelines for Interruption and Restart of 
INCB054828), guidance regarding restarting study drug at "25% reduction if in 
expansion, rounded down to the nearest tablet strength" has been deleted. 
Rationale for change:  Dose reductions are limited to doses tested (13.5 mg down to 
9 mg; 9 mg down to 6 mg). 
9. Section 5.7.3, Management of Hyperphosphatemia (Table 6) 
Description of change:  Language has been added to Table 6 (Recommended Approach 
for Hyperphosphatemia Management) for subjects receiving INCB054828 as a 
continuous dose. 
Rationale for change:  To provide guidance for subjects receiving the continuous 
administration regimen. 


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10. Section 5.8.1, Withdrawal Criteria 
Description of change:  Language has been added to allow subjects to continue 
receiving INCB054828 even after progressive disease is noted. 
Rationale for change:  In cases where the investigator believes the subject is receiving 
benefit and there are no other treatment options, this added language will allow subjects 
to continue to receive study drug, with medical monitor approval. 
11. Section 10.1, Investigational Product Description 
Description of change:  Language has been modified for INCB054828 labeling and 
storage requirements. 
Rationale for change:  Study is no longer US only and has been modified for rest-of-
world language requirements. 
12. Appendix A, Information Regarding Effectiveness of Contraceptive Methods 
Description of change:  Appendix A has been changed to include Clinical Trial 
Facilitation Group contraception methods. 
Rationale for change:  Updated with approved contraception language. 
13. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 4 (09 MAR 2016) 
The primary purpose of this amendment is to adjust language in the Protocol to allow more 
flexibility for enrollment based on accumulated safety data.  The secondary purpose is to adjust 
the management guidelines for hyperphosphatemia (HP). 
1. Synopsis; Section 3, Subject Eligibility; Section 4.1, Overall Study Design 
Description of change:  The Part 2 indications of gastric cancer and endometrial cancer 
were revised to gastric/cholangiocarcinoma cancer and endometrial/breast cancer. 
Rationale for change:  To allow more flexibility for enrollment. 
2. Synopsis; Section 4.1.1, Pharmacodynamic Target 
Description of change:  Revised as follows:  "The PAD is defined as the point where 
approximately 67% (2 out of 3) of subjects attain HP; in a cohort of 3 subjects, if 2 out of 
3 have HP, the cohort will be expanded to 6 (while dose escalation continues as 
described above).  Once the PADthis target is achieved in a cohort of 6 subjects…"  
Rationale for change:  To allow more flexibility for enrollment and management 
parameters associated with HP. 
3. Synopsis; Section 4.1.1.2, Recommended Part 2 Dose 
Description of change:  Revised to indicate that the recommended Phase 2 dose(s) 
(RP2D[s]) will be the lower of the maximum tolerated dose (MTD) or the 
pharmacologically active dose (PAD) with or without prophylactic concomitant 
phosphate binders. 
Rationale for change:  To allow more flexibility for enrollment and management 
parameters associated with HP. 
4. Synopsis; Section 4.1.2, Part 2 Dose Expansion; Section 5.7.3, Management of 
Hyperphosphatemia 
Description of change:  In the Synopsis and Section 4.1.2, specific guidelines for 
subjects who attain HP were replaced with a cross-reference to Section 5.7.3.  In 
Section 5.7.3, Table 3 (Recommended Approach for Hyperphosphatemia Management) 
was updated.  The serum phosphate level column was revised to include 3 levels:  
1) > 5.5 mg/dL and  ≤ 7 mg/dL, 2) > 7 mg/dL and ≤ 10 mg/dL, and 3) > 10 mg/dL, and 
the recommended approach for each was revised. 
Rationale for change:  To adjust the threshold for initiating phosphate binder use; this 
will allow more flexibility for the management parameters associated with HP. 


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5. Synopsis; Section 3.2, Subject Inclusion Criteria; Section 6, Study Assessments 
(Table 4) 
Description of changes:   
• Inclusion criterion 3 was revised to indicate that Part 2 subjects must have measurable 
disease with documented fibroblast growth factor/fibroblast growth factor receptor 
(FGF/FGFR) alteration in tumor types. 
• Inclusion criterion 7 was revised to indicate that subjects with archival tumor samples 
older than 2 years old and/or with sequencing report from Foundation Medicine 
require approval from the sponsor medical monitor for exemption from the need for 
tumor biopsy or tumor sample requirement.  This was also noted in Table 4, 
footnote h. 
Rationale for changes:  
• Inclusion criterion 3:  To state requirement for measurable disease in Part 2. 
• Inclusion criterion 7:  To provide biopsy sample flexibility for subjects who have 
existing Foundation Medicine genetic sequencing reports. 
6. Synopsis; Section 3.3, Subject Exclusion Criteria 
Description of changes: 
• Exclusion criterion 1 was clarified to indicate that subjects who have received 
treatment with other investigational study drug or anticancer medications may be 
eligible with the sponsor's medical monitor approval. 
• Exclusion criterion 3 (laboratory parameters outside Protocol-defined range) 
Part 1 Dose Escalation: 
− Criteria 3d-f revised to indicate total bilirubin, AST/ALT, and ALP parameters 
> upper limit of normal (ULN) excluded unless associated with subject's primary 
cancer and/or metastases and with medical monitor approval. 
− Criterion 3g revised to indicate creatinine clearance < 30 mL/min for urothelial 
carcinoma. 
− Criteria 3h and j (serum calcium and serum albumin) combined to indicate serum 
calcium outside of the institutional normal range, or serum albumin-corrected 
calcium outside of the institutional normal range if serum albumin is outside of 
the institutional normal range. 
Part 2 Expansion: 
− Criteria 3d-e revised to indicate total bilirubin, AST/ALT, and ALP > upper limit 
of normal (ULN), and excluded unless associated with subject's primary cancer 
and/or metastases and with medical monitor approval. 
− Criterion 3g revised to indicate creatinine clearance ≤ 40 mL/min (< 30 mL/min 
for multiple myeloma or urothelial carcinoma)  


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Part 3 Combination: 
− Criteria 3d-f revised to indicate total bilirubin, AST/ALT and ALP > upper limit 
of normal (ULN), and excluded unless associated with subject's primary cancer 
and/or metastases and with medical monitor approval. 
− Criterion 3g revised to indicate creatinine clearance ≤ 40 mL/min (< 30 mL/min 
for urothelial carcinoma). 
− Criterion 3h revised to indicated international normalized ratio or prothrombin 
time > 1.5 × ULN, unless on warfarin. 
Rationale for changes:   
• Exclusion criterion 1:  To provide more flexibility for enrollment. 
• Exclusion criterion 3:  To provide more flexibility for enrollment based on abnormal 
laboratory parameters that may be the result of the location of a subject's primary 
tumor or metastases. 
7. Section 1.4.2, Potential Risks of INCB054828 Based on Preliminary Clinical 
Experience 
Description of change:  Preliminary safety data have been updated. 
Rationale for change:  To provide investigators with current information. 
8. Section 3, Subject Eligibility  
Description of change:  Updated to indicate that deviations from eligibility criteria are 
not allowed because they can potentially jeopardize the scientific integrity of the study, 
regulatory acceptability, and/or subject safety.  Therefore, adherence to the criteria as 
specified in the Protocol is essential. 
Rationale for change:  New standard language in all Incyte Protocols regarding waivers. 
9. Section 5.6, Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose 
(Table 1) 
Description of change:  In Table 1 (Definition of Dose-Limiting Toxicity and Maximum 
Tolerated Dose of INCB054828), the nonhematologic toxicity section was updated to 
indicate "Asymptomatic changes in cholesterol and triglycerides," and "asymptomatic 
changes in lipid profiles" was deleted.  The hyperphosphatemia section was updated to 
indicate "Serum phosphorus ≥ 10 mg/dL recurrent or persistent for more than 1 week 
despite appropriate management." 
Rationale for change:  To refine the HP management guidelines based on revised 
criteria for initiating treatment with binders. 
10. Section 5.7.4, Criteria for Permanent Discontinuation of INCB054828 
Description of change:  The list of unacceptable AEs was updated to include serum 
phosphate levels in line with Table 3 (Recommended Approach for Hyperphosphatemia 
Management). 
Rationale for change:  To refine the criteria for discontinuation based on the revised HP 
management guidelines  


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11. Section 6, Study Assessments (Tables 4-7) 
Description of changes:  In Tables 4 and 6 (schedules of assessments for solid 
tumors/MPN and multiple myeloma), efficacy assessments (radiologic tumor assessments 
and IMWG multiple myeloma disease response assessment) were deleted from 
Cycles 2-6 Day 1 and moved to Cycles 2-6 Day 15.  In Tables 5 and 7 (laboratory 
assessments for solid tumors/MPN and multiple myeloma), total urine collection was 
deleted from Cycle 1 Day 1. 
Rationale for changes:  To ensure consistency between tables and Protocol text. 
12. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the redline version of the 
amendment. 


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Amendment 3 (02 NOV 2015) 
The primary purpose of Amendment 3 is to add Part 3, Combination Therapy.  In Part 3, 
INCB054828 will be paired with 3 different treatment regimens that are already being used for 
cancer treatment.  Amendment 3 also contains changes to the inclusion/exclusion criteria and 
corrections to the Schedule of Assessment tables. 
1. Synopsis; Section 3.1, Study Population; Section 4.1, Overall Study Design; 
Section 4.1.3, Part 3 Combination Dose Finding and Expansion; Section 4.4, 
Number of Subjects; Section 5.1.2, Treatment Regimen for Gemcitabine + Cisplatin 
(Part 3 Only);  Section 5.1.3, Treatment Regimen for Docetaxel (Part 3 Only); 
Section 5.1.4, Treatment Regimen for Pembrolizumab (Part 3 Only)  
Description of change:  Language was added to each section to describe Part 3, 
Combination Therapy.  Combination therapies include gemcitabine + cisplatin, docetaxel, 
and pembrolizumab.  Figure 1 (study design) was revised to include Part 3, and the 
number of subjects was updated. 
Rationale for change:  Early exploration of INCB054828 in combination with different 
therapies in the treatment of different tumor types. 
2. Synopsis; Section 4.1.2, Part 2 Dose Expansion 
Description of change:  The definition of hyperphosphatemia was revised to serum 
phosphate > 5.5 mg/dL or at least 1.5-fold change from baseline. 
Rationale for change:  Some subjects will have significant changes in serum phosphate 
baseline, while others will exceed the 5.5 mg/dL threshold.  The high degree of 
variability in serum phosphate requires flexibility in declaring the PAD. 
3. Synopsis; Section 4.1.1.1.  Pharmacodynamic Target 
Description of change:  The pharmacodynamic endpoint is now defined as 
approximately 67% (2 out of 3 subjects) instead of 80% (5 out of 6 subjects). 
Rationale for change:  Some subjects will have significant changes in serum phosphate 
baseline, while others will exceed the 5.5 mg/dL threshold.  The high degree of 
variability in serum phosphate requires flexibility in declaring the PAD. 
4. Section 1.3.1,  Rationale for Combining INCB054828 With Chemotherapy and 
Programmed Cell Death-1 Inhibitor 
Description of change:  This new section was added with information on combining 
targeted therapies such as INCB054828 and chemotherapeutic and immunotherapeutic 
agents. 
Rationale for change:  To provide a rationale for the combination of INCB054828 with 
the different agents proposed in Part 3. 


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5. Section 1.4, Potential Risks; Section 1.5, Justification of Route, Dose Regimen, and 
Treatment Period 
Description of change:  New sections were added to the Introduction to outline the risks 
associated with INCB054828, gemcitabine and cisplatin, docetaxel, and pembrolizumab 
independently as well in combination, and to include dose and administration information 
for gemcitabine and cisplatin, docetaxel, and pembrolizumab. 
Rationale for change:  New agents are being added to the study in Part 3, and the 
potential risks and dose and administration information must be included. 
6. Synopsis; Section 2, Study Objectives and Purpose 
Description of change:  The study objectives were updated to include the combination 
therapies. 
Rationale for change:  Additional analyses will be performed to include data generated 
from subjects treated with the combination therapies. 
7. Synopsis; Section 3.2, Subject Inclusion Criteria; Section 3.3, Subject Exclusion 
Criteria  
Description of change:  Modifications were made to some of the inclusion/exclusion 
criteria and criteria were added for Part 3 subjects. 
Rationale for change:  To allow more flexibility in the inclusion/exclusion criteria and 
to add parameters for Part 3 subjects. 
8. Section 5.7.5, Management of Adverse Events Associated With Gemcitabine + 
Cisplatin, Docetaxel, or Pembrolizumab 
Description of change:  New section has been added to outline the management of 
adverse events associated with gemcitabine, cisplatin, docetaxel, and pembrolizumab.  
Institutional guidelines should be followed and/or each drug label should be consulted, 
and if needed, the sponsor medical monitor should be consulted. 
Rationale for change:  To provide instructions on how to handle adverse events or 
safety issues associated with the therapies that will be used in combination with 
INCB054828 in Part 3. 
9. Section 6, Study Assessments, Table 4: Schedule of Assessments (Solid Tumors and 
MPN) 
Description of changes:   
a) Deleted 3-day window on Cycle 1 Day 15. 
b) Contact IRT:  X's added on Days 8, 14, and 16 of Cycle 1; X deleted for Disease 
Status Follow-Up. 
c) INCB054828 in clinic:  deleted X in Cycles 2-6 Day 15 and Cycle 7+ Day 1. 
d) Gem + Cis in clinic:  added to D1, D8 and D15 for all cycles. 
e) Docetaxel in clinic:  added to Day 1 for all cycles. 
f) Pembrolizumab in clinic:  added to Day 1 for all cycles. 








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Amendment 2 (11 JUN 2015) 
The objective of this Protocol Amendment is to refine procedural language regarding 
pharmacokinetics (PK) and food effect, ophthalmologic examination frequency, ECG 
monitoring, and biopsy requirements.  
1. Synopsis; Section 5.1.1, Treatment Regimen; Section 7.7.1, Blood Sample Collection 
Description of change:  Per Protocol Amendment 1, subjects self-administer study drug 
without regard to meals except on days when PK is assessed.  In Amendment 2, language 
was added to ensure that subjects administer study drug after a 2-hour fast and then fast 
for another hour after taking their dose of study drug.  On days when PK samples will be 
collected, subjects will be asked to fast for 8 hours prior to taking study drug and then 
1 hour after taking study drug. 
Rationale for change:  Per FDA request.  Standardized language has been added 
regarding meals with respect to study drug administration and overnight fasting prior to 
PK draws. 
2. Section 6, Study Assessments (Tables 4 and 6, Schedule of Assessments); Section 
7.4.6, Comprehensive Eye Examination 
Description of change:  The timing for ophthalmologic testing during the treatment 
phase has been changed from every 4 cycles on Day 1 (± 14 days) to every 3 cycles 
(± 14 days) starting at Cycle 3 Day 1.  Additional eye examinations are allowed when 
medically justified (eg, vision change). 
Rationale for change:  The FDA requested more frequent ophthalmologic testing.  The 
change from every 4 cycles to every 3 cycles shifts the testing from once every 12 weeks 
to once every 9 weeks (± 14 days). 
3. Section 6, Study Assessments (Tables 4 and 6, Schedule of Assessments); Section 
7.4.5, Twelve-Lead Electrocardiogram 
Description of change:  The single 12-lead ECG was changed to a triplicate 12-lead 
ECG at each planned timepoint and will be matched as closely to the PK sampling time 
as possible. 
Rationale for change:  The triplicate methodology is to maximize tracing quality and 
minimize intrasubject variability that may occur due to placement of electrodes, subject 
movement, etc. 
4. Synopsis; Section 1.5, Justification of Route, Dose Regimen, and Treatment Period; 
Section 2.2, Secondary Objectives; Section 4.1, Overall Study Design; Section 6, 
Study Assessments (Tables 4-7, Schedule of Assessments and Laboratory 
Assessments); Section 7.7.2, Food-Effect Study (Part 2 Only)  
Description of change:  A food-effect study will be performed on a subset of subjects 
(n = 8) enrolled into Part 2 of the study.  On Cycle 2 Day 14, the subset of subjects will 
ingest a high-fat meal within 25 minutes, and study drug administration will begin 
5 minutes after completion of the meal. 
Rationale for change:  To study the impact of food on the PK of INCB054828. 


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5. Synopsis; Section 6, Study Assessments (Tables 5 and 7, Laboratory Assessments); 
Section 7.7, Pharmacokinetic Assessments; Section 7.9.4, Distribution of Subject 
Reminder Cards 
Description of change:  Pharmacokinetic sampling times have been revised to refine the 
determination of the half-life of INCB054828.  Serial sampling will be performed on 
Cycle 1 Day 1 and Day 14.  One additional sample collection was added on Cycle 1 
Day 16.  Subjects will now have blood drawn on Days 1, 2, 8, 14, 15, and 16 in Cycle 1 
only. 
Rationale for change:  The purpose of the additional blood draws is to better 
characterize the PK profile for INCB054828. 
6. Synopsis; Section 3, Subject Eligibility; Section 4.1, Overall Study Design; 
Section 4.1, Number of Subjects; Section 7.4.8, Evaluation of FGF and FGFR 
Genetic Alterations 
Description of change:  Language has been added to clarify that for Part 2 (Dose 
Expansion), subjects will be allowed to enroll in the study based on sequencing data 
generated by the local institution in which they are being treated.  However, all subjects 
will be evaluated via a central laboratory.  Additional subjects may be enrolled if a 
subject has been enrolled based on a genetic alteration identified per a local assay, but it 
was not confirmed with the central laboratory assay.  In addition, more subjects with 
tumor types other than what is defined in the Protocol will be allowed to participate in the 
expansion cohort, with medical monitor approval. 
Rationale for change:  The purpose of this change is to minimize the number of 
potential screen failures.  While it is understood that due to possible discordance between 
the local intuition's procedures and Foundation Medicine that there will still be a fair 
number of screen failures but pulling already sequenced subjects from each institution's 
database will increase the chance of eligible subjects being enrolled from the start.  The 
addition of the cohort for subjects with FGFR/FGF alterations not fitting to one of the 
named tumor types will allow exploration of other tumor types with this alteration for 
potential future indications. 
7. Synopsis; Section 3.2, Subject Inclusion Criteria; Section 3.3, Subject Exclusion 
Criteria 
Description of change:  Modifications have been made to the inclusion/exclusion 
criteria:  a) adjustments have been made to several laboratory parameter requirements for 
Part 1 and Part 2 (ie, hemoglobin, creatine clearance, total bilirubin); b) medical monitor 
approval is needed to enroll tumor types other than what is specified in the Protocol; 
c) subjects who require hemodialysis will be excluded from the study. 
Rationale for change:  The purpose of these changes are to ensure that the inclusion and 
exclusion criteria are not too stringent as to restrict otherwise viable subjects, but also 
maintain proper guidance for the safe enrollment of the right subjects for this study.  No 
signals have been seen in the study to date, nor have there been issues noted in other 
FGFRi trials or INCB54828 preclinical data. 


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8. Synopsis; Section 1.5, Justification of Route, Dose Regimen and Treatment Period; 
Section 4.1.2, Part 2 Expansion; Section 4.4, Number of Subjects 
Description of change:  The number of sites participating in the study has increased to 
approximately 15 sites.  The number of subjects participating in Part 2 (expansion) has 
increased to 50, which increases the total number of subjects to 90. 
Rationale for change:  The integration of the central laboratory review of all subject 
tissue samples for FGFR alterations in Part 2 may result in discordance in results between 
a local laboratory (which will allow entry into the study) and the central laboratory 
(which will be confirmatory).  This may result in different outcomes and may require 
replacement of subjects.  As such, the number of subjects for Part 2 has been increased. 
9. Synopsis; Section 4.2.2, Secondary Endpoints 
Description of change:  Addition of t½ to PK parameters being evaluated. 
Rationale for change:  Due to intersubject variability, formal assessment of t½ is needed 
to fully illustrate the PK profile of INCB54828. 
10. Section 6, Study Assessments (Tables 5 and 7, Laboratory Assessments, and Table 8,  
Laboratory Tests:  Required Analytes for All Indications) 
Description of change:  A pregnancy test has been added at the end of treatment. 
Rationale for change:  To ensure that the female subject has not become pregnant 
during the course of the study. 
11. Section 7.8, Pharmacodynamic Assessments (Table 12, Sample Collection Times for 
Pharmacodynamic Assessments) 
Description of change:  Adjustments have been made to the collection of samples.  
A timeframe range has now been provided as well as a shift from Day 15 to Day 14. 
Rationale for change:  The purpose of the change is to align with the PK sampling 
schedule change. 
12. Section 7.5, Efficacy Assessments 
Description of change:  Efficacy assessments have been moved from Day 15 to Day 14 
of each cycle. 
Rationale for change:  The shift from Day 15 to Day 14 allows for alignment with the 
last day of study drug administration. 
13. Section 6.4.1, Safety Follow-Up 
Description of change:  Language has been added regarding the steps needed to 
complete a subject enrolled on this study if the subject is starting a new anticancer 
therapy. 
Rationale for change:  Once a subject discontinues or completes the study and begins a 
new anticancer therapy, steps need to be completed to ensure that the full complement of 
data is collected for the study prior to the initiation of the new therapy. 


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14. Section 5.7.2, Criteria and Procedures for Interruption (Table 2, Guidelines for 
Interruption and Restart of Study Drug) 
Description of change:  The guidelines for interruption have been refined (eg, Hy's 
Law). 
Rationale for change:  The additional guidelines and parameters will ensure subject 
safety and provide clearer instructions for interrupting and discontinuing study drug. 
15. Section 5.10, Restricted Medications and Measures 
Description of change:  A sentence has been added to limit the use of proton pump 
inhibitors (PPIs) due to the possible impact of study drug PK profile. 
Rationale for change:  The pH level of stomach may impact the dissolution of 
INCB54828; therefore, extensive use of PPIs might adverse effect the PK profile of study 
drug. 
16. Incorporation of administrative changes.  Other minor, administrative changes have 
been incorporated throughout the Protocol and are noted in the red-line/strike-out version 
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Amendment 1 (19 NOV 2014) 
The objective of this Protocol Amendment is to address FDA's November 17, 2014, clinical 
deficiencies.  
1. Synopsis; Section 1.5, Justification of Route, Dose Regimen, and Treatment Period; 
Section 4.1.1, Part 1 Dose Escalation; Section 4.1.2, Part 2 Expansion (Figure 1: 
Study Design)  
Description of change:  The Protocol was updated to remove the duration of ≥ 1 week 
from the definition of hyperphosphatemia, such that once a subject develops 
hyperphosphatemia of any duration, in the accelerated titration portion of the study 
cohorts will be expanded to at least 3 subjects and subsequent dose escalations will be 
limited to 50%. 
Rationale for change:  Required by FDA. 
2. Synopsis; Section 3.3, Subject Exclusion Criteria 
Description of change:  Exclusion criteria for subjects to be enrolled in Part 2 was 
updated to exclude subjects with a creatinine clearance ≤ 70 mL/min and also exclude 
subjects with serum calcium, serum phosphorus, and parathyroid hormone values outside 
of the institutional normal range.  The creatinine clearance criterion in Part 1 was updated 
to be ≤ 70 mL/min rather than < 70 mL/min to be in alignment with the Part 2 exclusion 
criterion. 
Rationale for change:  Required by FDA. 
3. Section 1.5, Justification of Route, Dose Regimen, and Treatment Period; 
Section 5.7.2, Criteria and Procedures for Interruption (Table 2: Guidelines for 
Interruption and Restart of Study Drug); Section 5.7.3, Management of 
Hyperphosphatemia (Table 3: Recommended Approach for Hyperphosphatemia 
Management); Section 6, Study Assessments (Table 5: Laboratory Assessments, and 
Table 7: Laboratory Assessments [Multiple Myeloma]); Section 7.4.7, Laboratory 
Assessments 
Description of change:  Protocol was updated to monitor calcium and phosphorus levels 
at least twice weekly in subjects who have abnormal levels on-study. 
Rationale for change:  Required by FDA. 
4. Section 3.1, Study Population 
Description of change:  Added clarification to state that in addition to progressing on at 
least 1 line of therapy, subjects should have no further effective standard anticancer 
therapy available to be consistent with wording elsewhere in the Protocol. 
Rationale for change:  Required by FDA. 


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5. Section 5.6, Dose-Limiting Toxicity and Determination of Maximum Tolerated Dose 
(Table 1: Definition of Dose-Limiting Toxicity and Maximum Tolerated Dose) 
Description of change:  Added Grade 3 thrombocytopenia with bleeding as a dose-
limiting toxicity.  Also, to be consistent with wording elsewhere in the Protocol, added a 
note in this table stating that transient (≤ 72 hours) abnormal laboratory values without 
associated clinically significant signs or symptoms based on investigator determination 
will not be considered a dose-limiting toxicity. 
Rationale for change:  Required by FDA. 
6. Section 5.7.4, Criteria for Permanent Discontinuation of Study Drug 
Description of change:  New criteria were added to require discontinuation of study 
drug upon evidence of disease progression or a concurrent elevation of ALT > 3 × ULN 
and total bilirubin > 2 × ULN in subjects who do not have evidence of biliary obstruction 
or other causes that can reasonably explain the concurrent elevations. 
Rationale for change:  Required by FDA. 
7. Section 5.11, Prohibited Medications and Measures 
Description of change:  Calcium-based phosphate-binding medications were added to 
the prohibited medication list. 
Rationale for change:  Required by FDA. 
8. Section 6, Study Assessments (Table 4:  Schedule of Assessments, and 
Table 6:  Schedule of Assessments [Multiple Myeloma]); Section 7.2, Interactive 
Response Technology Procedure 
Description of change:  An additional procedure was added to the study assessments 
tables to require sites to contact the IRT system.  Associated language was also added in 
Section 7.2. 
Rationale for change:  The Protocol was updated to include the use of IRT for the 
management of study drug supply. 
9. Section 6, Study Assessments (Table 4:  Schedule of Assessments, and 
Table 6:  Schedule of Assessments [Multiple Myeloma]) 
Description of change:  Comprehensive physical examinations were added at Cycle 2 
Day 1 and Day 1 of subsequent cycles. 
Rationale for change:  Required by FDA. 
10. Section 6, Study Assessments (Table 4:  Schedule of Assessments, footnote m); 
Section 6.4.2, Disease Status Follow-up 
Description of change:  Added clarification to state that the relevant disease response 
assessment should be performed in subjects who discontinue study treatment for a reason 
other than disease progression in the disease status follow-up phase. 
Rationale for change:  Clarification was needed to specify that the relevant disease 
response assessment should be used to continue to monitor disease status. 

SAP_001.pdf: 


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STATISTICAL ANALYSIS PLAN 
 
INCB 54828-101 
A Phase 1/2, Open-Label, Dose-Escalation, Safety and Tolerability 
Study of INCB054828 in Subjects With Advanced Malignancies 
(FIGHT-101) 
 
 
 
 
IND Number: 
 
EudraCT Number: 
2016-002831-14 
Sponsor: 
Incyte Corporation 
1801 Augustine Cut-Off 
Wilmington, DE 19803 
Protocol Version: 
Protocol Amendment 8 (11 DEC 2018) 
CRF Approval Date: 
05 FEB 2019 
SAP Version: 
Amendment 1 
SAP Author:  
 
 
Date of Plan: 
12 JUN 2019 
 
 
This study is being conducted in compliance with good clinical practice, 
including the archiving of essential documents. 
 


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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS ..........................................................................................................6 
1. 
INTRODUCTION ........................................................................................................8 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS.................................8 
2.1. 
Protocol and Case Report Form Version ......................................................................8 
2.2. 
Study Objectives ...........................................................................................................8 
2.2.1. 
Primary Objectives .......................................................................................................8 
2.2.2. 
Secondary Objectives ...................................................................................................8 
 
9 
2.3. 
Study Endpoints ............................................................................................................9 
2.3.1. 
Primary Endpoints ........................................................................................................9 
2.3.2. 
Secondary Endpoints ....................................................................................................9 
 
9 
3. 
STUDY DESIGN .......................................................................................................10 
3.1.1. 
Part 1 Dose Escalation ................................................................................................10 
3.1.1.1. 
Continuous Administration of INCB054828 ..............................................................11 
3.1.1.2. 
Renal Impairment .......................................................................................................11 
3.1.1.3. 
Pharmacodynamic Target ...........................................................................................11 
3.1.1.4. 
Recommended Part 2 Dose for Monotherapy.............................................................11 
3.1.1.5. 
Lower Dose Level Expansion .....................................................................................12 
3.1.2. 
Part 2 Dose Expansion ................................................................................................12 
3.1.3. 
Part 3 Combination Dose Finding and Expansion ......................................................12 
3.2. 
Randomization ............................................................................................................13 
3.3. 
Control of Type I Error ...............................................................................................13 
3.4. 
Sample Size Considerations........................................................................................14 
3.5. 
Schedule of Assessments ............................................................................................14 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS ..................................14 
4.1. 
Scheduled Study Evaluations and Study Periods .......................................................14 
4.1.1. 
Day 1 ...........................................................................................................................14 
4.1.2. 
Study Day ...................................................................................................................14 
4.1.3. 
Baseline Value ............................................................................................................15 
4.1.4. 
Cycle Length and Duration .........................................................................................15 


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4.1.5. 
Analysis Window........................................................................................................15 
4.1.6. 
Handling of Missing and Incomplete Data .................................................................15 
4.2. 
Variable Definitions....................................................................................................16 
4.2.1. 
Age ..............................................................................................................................16 
4.2.2. 
Body Mass Index ........................................................................................................16 
4.2.3. 
Body Surface Area ......................................................................................................16 
4.2.4. 
Prior and Concomitant Medication .............................................................................16 
5. 
STATISTICAL METHODOLOGY ...........................................................................17 
5.1. 
General Methodology .................................................................................................17 
5.2. 
Treatment Groups .......................................................................................................17 
5.3. 
Analysis Populations...................................................................................................17 
5.3.1. 
Efficacy Evaluable Population....................................................................................17 
5.3.2. 
Safety Population ........................................................................................................17 
5.3.3. 
Pharmacokinetic/Pharmacodynamic Population ........................................................18 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES................................................................................................................18 
6.1. 
Demographics and Baseline Characteristics, and Disease History.............................18 
6.1.1. 
Demographics and Baseline Characteristics ...............................................................18 
6.1.2. 
Disease History ...........................................................................................................18 
6.1.3. 
Prior Therapy ..............................................................................................................18 
6.1.4. 
Medical History ..........................................................................................................18 
6.2. 
Disposition of Subjects ...............................................................................................19 
6.3. 
Protocol Deviations.....................................................................................................19 
6.4. 
Exposure .....................................................................................................................19 
6.5. 
Study Drug Compliance..............................................................................................20 
6.6. 
Prior and Concomitant Medication .............................................................................20 
7. 
EFFICACY .................................................................................................................20 
7.1. 
Efficacy Hypotheses ...................................................................................................20 
7.2. 
Analysis of Efficacy Parameters .................................................................................20 
7.2.1. 
Response Assessment .................................................................................................20 
7.2.2. 
Best Overall Response and Overall Response Rate....................................................21 
7.2.3. 
Change in Target Lesion Size .....................................................................................21 
7.2.4. 
Other Efficacy Analyses .............................................................................................22 


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.22 
 
22 
7.2.4.3. 
ECOG Performance Status .........................................................................................23 
7.3. 
Pharmacokinetic Analyses ..........................................................................................23 
8. 
SAFETY AND TOLERABILITY ..............................................................................24 
8.1. 
General Considerations ...............................................................................................24 
8.2. 
Adverse Events ...........................................................................................................24 
8.2.1. 
Adverse Event Definitions ..........................................................................................24 
8.2.2. 
Dose-Limiting Toxicities ............................................................................................24 
8.2.3. 
Clinically Notable Treatment-Emergent Adverse Events ..........................................25 
8.2.4. 
Adverse Event Summaries ..........................................................................................25 
8.3. 
Clinical Laboratory Tests............................................................................................27 
8.3.1. 
Laboratory Value Definitions .....................................................................................27 
8.3.2. 
Laboratory Value Summaries .....................................................................................27 
8.4. 
Vital Signs...................................................................................................................28 
8.5. 
Electrocardiograms .....................................................................................................28 
9. 
INTERIM ANALYSES ..............................................................................................29 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN ........................29 
10.1. 
Changes to Protocol-Defined Analyses ......................................................................29 
10.2. 
Changes to the Statistical Analysis Plan .....................................................................29 
10.2.1. 
Amendment 1..............................................................................................................29 
11. 
REFERENCES ...........................................................................................................30 
APPENDIX A. RESPONSE ASSESSMENT CRITERIA FOR MULTIPLE 
MYELOMA ................................................................................................................31 
APPENDIX B. RESPONSE ASSESSMENT CRITERIA FOR SUBJECTS WITH 
MYELOPROLIFERATIVE NEOPLASMS...............................................................33 
APPENDIX C. PLANNED TABLES, FIGURES, AND LISTINGS.........................................34 
 


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LIST OF TABLES 
 
23 
Table 2: 
Laboratory Parameters to Be Summarized .................................................................27 
Table 3: 
Criteria for Clinically Notable Vital Sign Abnormalities ...........................................28 
Table 4: 
Criteria for Clinically Notable Electrocardiogram Abnormalities .............................28 
Table 5: 
Statistical Analysis Plan Versions ..............................................................................29 
 
LIST OF FIGURES 
Figure 1: 
Study Design ...............................................................................................................13 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Term 
AE 
adverse event 
ALT 
alanine aminotransferase 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase  
AUC(0-τ) 
AUC from time zero (predose) to time of last observed quantifiable concentration 
within a subject across all treatments 
BMI 
body mass index 
BOR 
best overall response 
BSA 
body surface area 
CL/F 
apparent oral dose clearance 
Cmax 
maximum observed concentration 
Cmin 
minimum observed concentration 
CR 
complete response 
CRF 
case report form 
CSR 
Clinical Study Report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DLT 
dose-limiting toxicity 
 
 
ECG 
electrocardiogram 
ECOG 
Eastern Cooperative Oncology Group 
EOT 
end of treatment 
FDA 
Food and Drug Administration 
FGF 
fibroblast growth factor 
FGFR 
fibroblast growth factor receptor 
IMWG 
International Myeloma Working Group 
LLN 
lower limit of normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
MPN 
myeloproliferative neoplasm 
MTD 
maximum tolerated dose 
NE 
not evaluable 
ORR 
overall response rate 
PAD 
pharmacologically active dose 
PD 
pharmacodynamics or progressive disease 
 
 
PK 
pharmacokinetics 
PR 
partial response 
QD 
once daily 


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Abbreviation 
Term 
RECIST 
Response Evaluation Criteria in Solid Tumors 
RP2D 
recommended Part 2 dose 
SD 
stable disease 
SAP 
Statistical Analysis Plan 
SI 
International System of Units 
TEAE 
treatment-emergent adverse event 
ULN 
upper limit of normal 


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1. 
INTRODUCTION 
This is a Phase 1, open-label, dose-escalation, safety and tolerability study of the FGFR inhibitor 
INCB054828 in subjects with advanced malignancies.  The study will be conducted in 3 parts.  
Part 1 (monotherapy dose escalation) will determine the MTD of INCB054828 and/or 
doses/regimen that produce substantial evidence of pharmacologic target inhibition (increased 
serum phosphate).  Approximately 20 subjects with moderate and severe renal impairment will 
be enrolled in Part 1 for safety and PK evaluation.  Part 2 (monotherapy dose expansion) will 
evaluate the dose(s) selected in Part 1 as a monotherapy in specific indications where activity of 
FGFR is particularly relevant.  Approximately 8 subjects enrolled in Part 2 will participate in a 
food-effect study.  Part 3 will begin with dose-finding to determine recommended expansion 
doses of INCB054828 in combination with gemcitabine + cisplatin, docetaxel, pembrolizumab, 
trastuzumab, or INCMGA00012 in subjects for which these treatments or PD-1–directed 
treatment is relevant.  Dose-expansion will further evaluate the dose(s) selected in these 
populations harboring FGF/FGFR alterations. 
A detailed description of the investigational product, target patient population, rationale for doses 
to be examined, and potential risks and benefits of treatment with INCB054828 is provided in 
the Protocol, Section 1.  The purpose of this SAP is to define the methodology for analyzing and 
summarizing the data collected during the conduct of Study INCB 54828-101. 
2. 
STUDY INFORMATION, OBJECTIVES, AND ENDPOINTS 
2.1. 
Protocol and Case Report Form Version 
This SAP is based on INCB 54828-101 Protocol Amendment 8 (11 DEC 2018) and CRFs 
approved on 05 FEB 2019.  Unless superseded by an amendment, this SAP will be effective for 
all subsequent Protocol amendments and CRF versions. 
2.2. 
Study Objectives 
2.2.1. 
Primary Objectives 
 To evaluate the safety, tolerability, and DLTs and to determine the PAD and MTD of 
INCB054828, alone as a monotherapy and in combination with other therapies. 
 To assess the pharmacodynamics of INCB054828.  
2.2.2. 
Secondary Objectives 
 To assess preliminary efficacy by assessing the ORR of INCB054828 in subjects with 
measurable disease, alone as a monotherapy and in combination with other therapies. 
 To evaluate the PK of INCB054828 and the effect of food and other therapies on the 
PK of INCB054828. 




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3. 
STUDY DESIGN 
This is an open-label, dose-escalation study of the FGFR inhibitor INCB054828 in subjects with 
advanced malignancies.  Subjects will receive QD doses of INCB054828 on a 2-weeks-on 
therapy and 1-week-off therapy schedule; a continuous administration regimen will also be 
explored.  The study will be conducted in 3 parts (see Figure 1).  Part 1 (monotherapy dose 
escalation) will determine the MTD of INCB054828 and/or doses/regimen that produce 
substantial evidence of pharmacologic target inhibition (increased serum phosphate).  Part 2 
(monotherapy dose expansion) will evaluate the dose(s) and/or regimen selected in Part 1 as a 
monotherapy in specific indications where activity of FGFR is particularly relevant and that have 
amplification, mutation, or translocation of FGFR 1, 2, or 3, or alteration of FGF 1 through 23.  
In Part 1, approximately 20 subjects with moderate (n ≈ 10) and severe (n ≈ 10) renal impairment 
will be enrolled for safety and PK evaluation, with subjects with moderate renal impairment 
enrolled first. 
Additionally, as part of the dose expansion (Part 2), all subjects enrolling in the tumor-specific 
cohorts (n = 20 total, n = 5 per cohort) will have mandatory biopsies, and approximately 
8 subjects will participate in a food-effect study.  Part 3 will begin with dose-finding to 
determine RP2Ds of INCB054828 in combination with gemcitabine + cisplatin, docetaxel, 
pembrolizumab, trastuzumab, or INCMGA00012 in subjects for which these treatments or PD-
1–directed treatment is relevant.  Dose-expansion will further evaluate the RP2Ds selected in 
these populations harboring FGF/FGFR alterations, including up to 6 subjects per combination 
for mandatory baseline and on-treatment biopsies. 
Treatment may continue as long as subjects are receiving benefit and have not met any criteria 
for study withdrawal.  Subjects who discontinue study drug will continue to be followed for 
subsequent anticancer treatments and survival. 
3.1.1. 
Part 1 Dose Escalation 
Approximately 40 subjects will be enrolled in Part 1.  The study will begin with an open-label 
dose escalation with an accelerated titration design based on observing each dose level for a 
period of 21 days before enrolling the next cohort and administering the next dose level.  In 
Part 1, subjects who receive at least 11 out of 14 doses of study drug at the level assigned to that 
cohort or have a DLT will be considered evaluable for determining tolerability of the dose.  
Subjects enrolling but not meeting these criteria may be replaced in order to fill the cohort. 
The starting dose of INCB054828 will be 1 mg QD.  The initial cohorts will consist of at least 
1 subject each, and the doses may be increased up to 2-fold in successive cohorts until a Grade 2 
or greater toxicity (excepting toxicities with a clear alternative explanation [eg, due to disease 
progression] or transient [≤ 72 hours] abnormal laboratory values without clinically significant 
signs or symptoms) or HP (serum phosphate > 5.5 mg/dL) is observed, at which time that cohort 
will be expanded to at least 3 subjects.  From the point where a single-subject cohort is first 
expanded to 3 subjects, subsequent cohorts will enroll at least 3 subjects, and increases to study 
drug dose will be limited to no more than 50% in successive cohorts.  If no DLTs are observed in 
the initial 3 subjects, the next cohort will begin enrollment.  If 1 DLT is observed in the first 
3 subjects, 3 additional subjects will be enrolled in the cohort.  If a DLT occurs in 2 or more 


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subjects in a cohort of 3 or 6, then the MTD will be deemed to have been exceeded, and the next 
lower dose level will be deemed to be the MTD.  Thus, the MTD will be defined as 1 dose level 
below that at which one-third or more of subjects in a particular cohort report a DLT.  If a DLT 
is observed at the initial dose of 1 mg QD, then a dose decrease to 0.5 mg may be considered.  
An intermediate dose level may also be explored.  If toxicities specifically relevant to a type of 
malignancy are observed, a separate dose escalation or de-escalation group will be initiated for 
subjects with this malignancy. 
3.1.1.1. 
Continuous Administration of INCB054828 
Continuous study drug administration will be tested in separate dose-escalation cohorts both in 
monotherapy cohorts and combination cohorts.  The starting dose of continuous administration 
will be lower than the MTD identified in the 2-weeks-on therapy/1-week-off therapy schedule.  
Subjects who receive at least 18 of 21 doses of study drug at the level assigned to that cohort or 
who have a DLT will be considered evaluable for determining tolerability of the dose.  Subjects 
enrolling but not meeting these criteria may be replaced in order to fill the cohort. 
3.1.1.2. 
Renal Impairment 
A subgroup of approximately 20 subjects (approximately 10 subjects with moderate renal 
impairment and 10 with severe renal impairment) will be enrolled in Part 1 at the 13.5 mg 
continuous administration regimen to assess the effect of renal impairment on the safety and PK 
of INCB054828. 
3.1.1.3. 
Pharmacodynamic Target 
Dose escalation will proceed in the absence of an MTD to a PAD.  The PAD is defined as the 
point where approximately 67% of subjects (2 out of 3) attain HP; in a cohort of 3 subjects, if 
2 out of 3 have HP, the cohort will be expanded to 6 (while dose escalation continues as 
described above).  Once the PAD is achieved, a new cohort will be enrolled where subjects will 
be treated with diet modification (decreased phosphate intake) and phosphate binders, and dose 
escalation will continue to determine the dose at which at least one-third of subjects attain HP 
and an MTD is identified.  Alternative PAD can be defined by molecular endpoint such as the 
inhibition of FGFR and/or at least a 1.5-fold increase of serum phosphate. 
3.1.1.4. 
Recommended Part 2 Dose for Monotherapy 
The RP2D (dose and/or regimen) will be the lower of the MTD or the PAD with or without 
concomitant phosphate binders; different RP2Ds may be determined for interval administration 
and continuous administration.  Multiple RP2Ds may be used going into Part 2 and Part 3. 


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3.1.1.5. 
Lower Dose Level Expansion  
Up to 3 additional subjects may be enrolled at any dose level for the interval and continuous 
administration monotherapy regimens, as well as the combination regimens, that is deemed to be 
pharmacodynamically active (HP observed in two-thirds of treated subjects) if that dose level is 
below the MTD.  Subjects must have FGF/FGFR alteration and are required to have a baseline 
and on-treatment tumor biopsy and at least 1 on-treatment biopsy (recommended at Cycle 2 
Day 14 but allowed to be performed at any cycle; must be performed on a study drug 
administration day, preferably between Day 8 and Day 14).  Additionally, an end of treatment 
(EOT)/at time of progression biopsy is requested but not required.  
 
 
3.1.2. 
Part 2 Dose Expansion 
When the recommended doses and/or regimen for the investigation in Part 2 have been 
determined, enrollment will proceed for Part 2.  It is possible that a different dose and/or regimen 
will be chosen for subjects with different types of malignancies. 
Approximately 140 subjects will be treated in expansion groups to further determine safety, 
tolerability, efficacy, PK, food effect (n ≈ 8), and PD in specific populations.  In addition, all 
subjects enrolling in the tumor-specific cohorts (n = 20 total, n = 5 per cohort) will have 
mandatory biopsies. 
Subjects who attain HP should follow guidelines for HP management guidelines as per Protocol.  
Subjects that do not attain HP or at least a 1.5-fold increase in serum phosphate after the first 
cycle of treatment should have their dose increased each cycle to the previously study assessed 
dose until HP or the maximum safely tested dose/MTD is reached. 
3.1.3. 
Part 3 Combination Dose Finding and Expansion   
Part 3 will comprise treatment groups evaluating INCB054828 when administered in 
combination with standard therapies for select solid tumors.  Part 3 will include dose finding and 
dose expansion.  Dose finding will be a 3 + 3 enrollment design that will evaluate different doses 
of INCB054828 in combination with agents utilized in the treatment of solid tumors.  The dose 
expansion is to further evaluate the safety and preliminary efficacy of the combination in select 
tumor types at the selected INCB054828 dose. 
Approximately 60 subjects will be enrolled in the dose-finding group.  The starting dose for 
Part 3 will be the RP2D(s). 
Initially, at least 3 subjects will be enrolled in each treatment group for dose finding.  The 
treatment groups include INCB054828 in combination with gemcitabine/cisplatin, docetaxel, 
pembrolizumab, trastuzumab, or INCMGA00012.  If in each group no DLTs are observed, then 
enrollment of the corresponding expansion will begin.  If 1 DLT is observed, then at least 
6 subjects will be enrolled in the dose-finding treatment group.  If DLTs are observed in 2 or 
more subjects in a 3- or 6-subject group, then the dose of INCB054828 will be reduced by 25% 
to 50%.  Dose assessment and de-escalation may be repeated once more.  The combination MTD 
will be the highest dose of INCB054828 in each combination at which ≤ 0/3 or 1/6 subjects 
experience DLTs.  The recommended combination expansion dose will be a dose less than or 
equal to the MTD/PAD dependent on emergent pharmacodynamics, PK, and safety data and may 




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3.4. 
Sample Size Considerations 
Approximately 325 subjects will be enrolled into this study.  Part 1 of the study is a standard 
dose-escalation design, and the sample size depends on the occurrence of safety findings such as 
DLTs.  Approximately 1 to 6 subjects will be enrolled in each dose level.  For Part 2, 
approximately 140 subjects will be enrolled, which will provide > 90% chance of detecting at 
least 17 responders if the underlying response rate is 30%.  For Part 3, approximately 3 to 
6 subjects will be enrolled per combination therapy for dose finding, and approximately 
24 subjects per combination therapy for dose expansion (except for the docetaxel and 
trastuzumab cohorts), which will provide > 90% chance of detecting at least 4 responders in 
expansion group if the underlying response rate is 30%. 
3.5. 
Schedule of Assessments 
See Protocol Amendment 8 (11 DEC 2018) for a full description of all study procedures and 
assessment schedules for this study. 
4. 
DATA HANDLING DEFINITIONS AND CONVENTIONS 
4.1. 
Scheduled Study Evaluations and Study Periods 
4.1.1. 
Day 1 
Day 1 is the date that the first dose of study drug (INCB054828 or combination agent) is 
administered to the subjects. 
4.1.2. 
Study Day 
If a visit/reporting date is on or after Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date + 1).  
If the visit/reporting date is before Day 1, then the study day at the visit/reporting date will be 
calculated as  
Day # = (Visit/Reporting Date – Day 1 date).  
A study day of -1 indicates 1 day before Day 1. 


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4.1.3. 
Baseline Value 
Baseline is the last non-missing measurement obtained before the first administration of 
INCB054828 or combination agent, unless otherwise defined.  When scheduled assessments and 
unscheduled assessments occur on the same day and time of the assessment or time of first dose 
is not available, use the following convention to determine baseline: 
 If both a scheduled and an unscheduled visit are available on the day of the first dose 
and the time is missing, use the scheduled assessment as baseline. 
 If all scheduled assessments are missing on the day of the first dose and an 
unscheduled assessment is available, use the unscheduled assessment as baseline. 
4.1.4. 
Cycle Length and Duration 
Cycle 1 Day 1 is defined as the day of the first dose of INCB054828.  One treatment cycle 
consists of 21 days, with first day of each cycle corresponding with the first day of INCB054828 
administration in that cycle.  
4.1.5. 
Analysis Window 
For parameters that will be summarized by visit, the nominal visit as recorded on the electronic 
CRF will be used.  There will be no additional analysis windowing done based on the assessment 
date. 
4.1.6. 
Handling of Missing and Incomplete Data  
In general, values for missing data will not be imputed unless methods for handling missing data 
are specified in this section or relevant sections.  
Partial disease/cancer diagnosis date will be handled as follows:  
 If only the day is missing, then the imputed day will be the first of the month.  
 If both the month and day are missing, then the imputed day and month will be 
01 JAN.  
 No imputation will be done if the date is completely missing.  
For relevant efficacy endpoints, partial death date will be imputed as follows:  
 If mmyyyy for the last contact date = mmyyyy for the death date, then the death date 
will be set to the day after the last contact date.  
 If mmyyyy for the last contact date < mmyyyy for the death date, then the death date 
will be set to the first day of the death month.  
 Otherwise, the partial death date will not be imputed.  


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4.2. 
Variable Definitions 
The following variables will only be calculated if not reported on the CRF.  
4.2.1. 
Age 
Subject age will be calculated as the integer part of the number of years from date of birth to the 
date of signing the ICF, using the following formula: 
Age = integer part of (date of informed consent – date of birth + 1) / 365.25 
4.2.2. 
Body Mass Index 
Body mass index will be calculated as follows: 
BMI (kg/m2) = [weight (kg)] / [height (m)]2 
4.2.3. 
Body Surface Area 
Body surface area will be calculated based on the Mosteller (1987) formula as follows: 
BSA (m2) = {[weight (kg)  height (cm)] / 3600}½ 
Sites will also record the BSA calculated per institutional standards. 
4.2.4. 
Prior and Concomitant Medication 
Prior medication is defined as any nonstudy medication started before the first dose of 
INCB054828 or combination agent. 
Concomitant medication is defined as any nonstudy medication that is started accordingly:  
 Before the date of first administration of INCB054828 or combination agent and is 
ongoing throughout the study or ends on/after the date of first study drug 
administration. 
 On/after the date of first administration of INCB054828 or combination agent and is 
ongoing or ends during the course of study drug. 
A prior medication could also be classified as "both prior and concomitant medication" if the end 
date is on or after first dose of INCB054828/combination agent.  In the listing, it will be 
indicated whether a medication is prior-only, concomitant-only, or both prior and concomitant 
medication. 
For the purposes of analysis, all medications will be considered concomitant medications unless 
the medications can unequivocally be defined as not concomitant. 


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5. 
STATISTICAL METHODOLOGY 
5.1. 
General Methodology 
Unless otherwise noted, SAS software (SAS Institute Inc, Cary, NC; v9.4 or later) will be used 
for the generation of all tables, graphs, and statistical analyses.  Descriptive summaries for 
continuous variables will include, but not be limited to, the number of observations, mean, 
standard deviation, median, minimum, and maximum.  Descriptive summaries for categorical 
variables will include the number and percentage of subjects in each category.  Analyses of PK 
endpoints are described in Section 7.3, and will be performed by the Incyte pharmacokineticist. 
5.2. 
Treatment Groups 
This is a Phase 1, open label, dose escalation and expansion study. 
Safety data from Part 1 and Part 2 will be combined and summarized overall and by dose 
levels/regimen based on actual treatment received on Day 1.  In the event that several dose levels 
tested are deemed substantially below the MTD, these doses may be combined for summary 
purposes. 
Safety data from Part 3a and Part 3b will be combined and summarized by dose 
levels/regimen/combination therapy based on actual treatment received on Day 1.  In the event 
that several dose levels tested are deemed substantially below the MTD, these doses may be 
combined for summary purposes. 
Efficacy data from Part 2 and Part 3b will be summarized separately. 
5.3. 
Analysis Populations 
5.3.1. 
Efficacy Evaluable Population 
The Efficacy Evaluable Population includes all subjects enrolled in the study who received at 
least 1 dose of INCB054828 or combination agent.  Treatment groups for this population will be 
determined according to the actual treatment the subject received on Day 1.  Demographics, 
baseline characteristics, subject disposition, and all the efficacy analyses will be conducted using 
the efficacy evaluable population. 
5.3.2. 
Safety Population 
The Safety Population includes all subjects enrolled in the study who received at least 1 dose of 
INCB054828 or combination agent.  Treatment groups for this population will be determined 
according to the actual treatment the subject received on Day 1.  All safety analyses will be 
conducted using the safety population. 


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5.3.3. 
Pharmacokinetic/Pharmacodynamic Population 
The PK/pharmacodynamics population will include all subjects who received at least 1 dose of 
INCB054828 or combination agent and provided at least 1 postdose plasma sample 
(1 PK/pharmacodynamics measurement).  The study pharmacokineticist will review data listings 
of subject dosing and sample records to identify subjects to be excluded from analyses of PK 
data.  The study research investigator will review data listings of pharmacodynamics data and 
sample records to identify subjects to be excluded from analyses of pharmacodynamics data. 
6. 
BASELINE, EXPOSURE, AND DISPOSITION VARIABLES AND 
ANALYSES 
Appendix C provides a list of planned tables, figures, and listings. 
6.1. 
Demographics and Baseline Characteristics, and Disease History 
Demographic and baseline characteristics, disease history, and prior therapy will be summarized 
for the efficacy evaluable population and listed. 
6.1.1. 
Demographics and Baseline Characteristics 
Demographic and baseline characteristics includes age, sex, race, ethnicity, weight, height, BMI, 
BSA, ECOG performance status, FGFR status, and baseline phosphate. 
6.1.2. 
Disease History 
Cancer type, time since initial diagnosis, and staging at diagnosis will be summarized. 
Time since diagnosis will be calculated as:  
Time since diagnosis (years) = (Day 1 – date of diagnosis + 1) / 365.25.  
6.1.3. 
Prior Therapy 
Number of subjects who received prior systemic therapy and number of prior systemic therapies 
will be summarized for the efficacy evaluable population.  Regimen name, component drugs, 
start and stop dates, purpose of the regimen, best response, reason for discontinuation, and date 
of relapse/progression will be listed.  
Number of subjects who received prior radiation will be summarized for the efficacy evaluable 
population.  Radiotherapy type, body site, start and stop dates, total dose, and best response will 
be listed.  
Number of subjects who had prior surgery or surgical procedure for the malignancies under 
study will be summarized for the efficacy evaluable population.  Date and description of the 
surgery/procedure will be listed. 
6.1.4. 
Medical History 
For subjects in the efficacy evaluable population, medical history will be summarized by SOC 
and PT and will be listed. 


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6.2. 
Disposition of Subjects 
The number and percentage of subjects who were treated, discontinued study treatment with a 
primary reason for discontinuation, and discontinued from the study with a primary reason for 
withdrawal will be summarized for the efficacy evaluable population. 
6.3. 
Protocol Deviations 
Protocol deviations collected on the CRFs will be summarized descriptively and listed. 
6.4. 
Exposure 
For subjects in the safety population, exposure to INCB054828 will be summarized descriptively 
as the following: 
 Number of treatment cycles with INCB054828:  The number of cycles with a 
nonzero dose of INCB054828. 
 Duration of treatment with INCB054828: 
Duration of treatment (days) = Date of last dose of INCB054828 – Date of first dose 
of INCB054828 + 1  
 Average daily dose of INCB054828:  
Average daily dose of INCB054828 (mg/day) = [total actual INCB054828 dose taken 
(mg)] / [duration of treatment with INCB054828] 
Combination agent gemcitabine, cisplatin, docetaxel, pembrolizumab, trastuzumab, and 
INCMGA00012 in part 3 will be summarized descriptively as the following: 
 Number of treatment cycles:  The number of cycles with a nonzero dose of study 
drug. 
 Average number of doses administered per cycle:  Total number of doses 
administered divided by number of cycles. 
 Relative dose intensity:  The ratio of the total actual dose administered to total 
assigned dose. 
Relative dose intensity (%) = 100 × [total actual dose] / [total assigned dose]  
Total actual dose (mg) administered is the sum of the dose that has been administered 
to the subject.  
Total assigned dose (mg) is the total dose expected if the subject had taken all doses 
as initially assigned. 


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6.5. 
Study Drug Compliance 
For subjects in the safety populations, overall compliance (%) for INCB054828 will be 
calculated for all subjects as: 
Overall Compliance (%) = 100  [total dose actually taken (mg)] / [total prescribed dose 
(mg)]. 
The total prescribed dose is defined as the sum of the doses prescribed by the investigator 
accounting for dose modifications. 
The total actual dose taken will be calculated based on information entered on the drug 
accountability CRF.  If there is dispensed drug that have not been returned yet, the actual dose 
taken starting from the dispense date of the unreturned drug will be imputed by the dose taken as 
reported on the dosing CRF. 
Compliance of INCB054828 will be summarized descriptively and listed. 
6.6. 
Prior and Concomitant Medication 
Prior medications and concomitant medications will be coded using the WHO Drug Dictionary.  
For subjects in the safety population, the number and percentage of subjects with prior and 
concomitant medications will be summarized by WHO drug class and WHO drug term.  In the 
data listing, each medication will be recorded as prior, concomitant, or both prior and 
concomitant. 
7. 
EFFICACY 
Appendix C provides a list of planned tables, figures, and listings. 
7.1. 
Efficacy Hypotheses 
Not applicable. 
7.2. 
Analysis of Efficacy Parameters 
7.2.1. 
Response Assessment 
Objective assessment of tumor status is required using appropriate disease-specific techniques, 
and the investigator's assessment will be used to determine responses and will be logged into the 
CRF.  For solid tumors, RECIST v1.1 will be used (Eisenhauer et al 2009). 
For multiple myeloma, the assessments will be based on the IMWG Multiple Myeloma response 
criteria (see Appendix A; Durie et al 2006). 
For subjects with MPNs, the response criteria in Appendix B will be used to assess response.  


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The schedule for efficacy assessments will be at screening (this will be considered the baseline 
scan) and every 3 cycles (starting with Cycle 3) throughout the study.  Efficacy assessments 
should occur at the end of the cycle.  Multiple myeloma subjects should have response 
assessments performed on Day 14 of every cycle (± 2 days).  Subjects with MPN should have a 
bone marrow aspirate and biopsy performed approximately 3, 6, and 12 months after Day 1 and 
then every 12 months on the nearest Cycle Day 14 (± 2 days) after the first dose of treatment and 
as clinically indicated.  
For subjects who discontinue treatment for reasons other than disease progression, every effort 
should be made to continue monitoring disease status until (1) start of new antineoplastic 
therapy, (2) documented disease progression, (3) death, or (4) the end of study, whichever occurs 
first.  
Response status per investigator's assessment will be recorded at each response assessment visit 
as CR, PR, SD, PD, NE for solid cancer and MPN; recorded as sCR, CR, VGPR, PR, SD, PD, 
and clinical relapse for myeloma.  
7.2.2. 
Best Overall Response and Overall Response Rate 
Best overall response is the best response postbaseline prior to and including the first PD, in the 
order of CR, PR, SD, PD, and NE for solid tumor and MPN, and in the order of sCR, CR, 
VGPR, PR, SD, and PD/relapse for myeloma.  In the case of SD for solid tumors, measurements 
must meet the SD criteria at least once on or after Day 42.  Subjects who fail to meet this 
criterion will have a BOR of PD if the next available tumor assessment after the initial scan 
indicates PD, or have a BOR of NE if there are no additional tumor assessments available.  
A subject with solid tumor or MPN is considered a responder if they have a BOR of CR or PR; a 
subject with myeloma is considered a responder if they have BOR of sCR, CR, VGPR, or PR. 
The ORR is the proportion of responders.  Subjects who do not have sufficient baseline or on-
study response assessment information to be adequately assessed for response status will be 
included in the denominators in the calculation of ORR. 
The ORR will be estimated with 95% CIs for the efficacy evaluable population.  Confidence 
intervals will be calculated based on the exact method for binomial distributions.  
The BOR will be summarized for the efficacy evaluable population.  Response assessment data 
on target and nontarget lesions and data leading to overall response assessment by visit will be 
listed. 
7.2.3. 
Change in Target Lesion Size  
For subjects with measurable lesions at baseline, target lesion sizes will be measured by sum of 
diameters.  The best percent change from baseline, defined as the largest decrease in target lesion 
size during the study, will also be summarized, and a waterfall plot of best percent change will 
be generated.  Note that for subjects who only have increases in target lesion size from baseline, 
the smallest increase will be considered as the best change from baseline. 


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Target lesions considered "too small to measure" will be assigned a default value of 5 mm for 
purposes of this analysis.  Likewise, target lesions identified as "not present" at postbaseline 
assessments will be assigned 0 mm for this analysis.  In the event a target lesion is unaccounted 
for in a particular postbaseline timepoint (ie, the assessment is missing or NE), then the overall 
sum of diameters for target lesions will not be evaluable for that postbaseline timepoint. 
 
 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
  
 
 
 


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7.2.4.3. 
ECOG Performance Status 
ECOG performance status at scheduled assessment times will be summarized. 
7.3. 
Pharmacokinetic Analyses 
The PK parameters of Cmax, tmax, Cmin, AUC0-t, t½, and Cl/F (INCB054828) will be calculated 
from the blood plasma concentrations of INCB054828 using standard noncompartmental 
(model-independent) PK methods and will be summarized by treatment group for the PK 
population.  Pharmacokinetic calculations will be performed, if appropriate, using commercial 
software such as WinNonlin® (Pharsight Corporation, Mountain View, CA).  Nominal times 
will be used in all cases, except when the difference between the actual time and nominal time is 
greater than 15 minutes for samples collected up to 4 hours after administration and greater than 
30 minutes for samples collected more than 4 hours after administration; in these cases, actual 
time will be used for PK analysis. 


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8. 
SAFETY AND TOLERABILITY 
Appendix C provides a list of planned tables, figures, and listings. 
8.1. 
General Considerations 
The analyses for this section will be provided for the safety population.  Summary tables may be 
replaced with listings when appropriate.  For instance, an AE frequency table may be replaced 
with a listing if it only contains a few unique preferred terms reported on relatively few subjects. 
8.2. 
Adverse Events 
8.2.1. 
Adverse Event Definitions 
A TEAE is any AE either reported for the first time or worsening of a pre-existing event after 
first dose of study drug and within 30 days of the last dose of study drug.  Analysis of AEs (as 
discussed below) will be limited to TEAEs, but data listings will include all AEs regardless of 
their timing to study drug administration. 
Adverse Events will be tabulated by the MedDRA preferred term and system organ class.  
Severity of AEs will be graded using the NCI CTCAE v4.03.  The CTCAE reporting guidelines 
and grading details are available on the Cancer Therapy Evaluation Program website.  
A grading (severity) scale is provided for each AE term.  If the toxicity is not included in the 
NCI CTCAE v4.03 criteria, it will be rated on a scale of 1 to 4 as follows:  1 = mild, 
2 = moderate, 3 = severe and 4 = life-threatening.  All toxicities will be graded based on the 
worst level reached, not the level they may have reached if they had not been treated.  When the 
intensity of an AE changes over time for a reporting period (eg, between visits), each change in 
intensity will be reported as an AE until the event resolves. 
The subset of AEs considered by the investigator to be related to study drug will be considered to 
be treatment-related AEs.  If the investigator does not specify the relationship of the AE to study 
drug, the AE will be considered to be treatment-related.  The incidence of AEs and treatment-
related AEs will be tabulated.   
Serious AEs will also be tabulated.  
Any missing onset date, causality, or severity must be queried for resolution.  Unsolved missing 
values will be handled according to the following rules: 
 An unsolved missing causality will be considered treatment related. 
 An unsolved missing severity will be identified as an unknown severity. 
For purposes of analysis, all AEs will be considered TEAEs unless the AE can unequivocally be 
defined as not treatment emergent. 
8.2.2. 
Dose-Limiting Toxicities 
The number of subjects with DLTs during the first cycle of study drug will be summarized, and 
DLTs will be listed by dose level. 


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8.2.3. 
Clinically Notable Treatment-Emergent Adverse Events 
Specific groupings of clinically notable TEAEs will be considered, and the number of subjects 
with at least 1 event will be reported.  Such groups consist of TEAEs for which there are specific 
clinical interests in connection with the study drug or TEAEs that are similar in nature (although 
not identical).  All clinically notable TEAEs are defined through reviewing preferred terms 
according to MedDRA v21.1. 
8.2.4. 
Adverse Event Summaries 
An overall summary of AEs by treatment group will include:   
 Number (%) of subjects reporting any TEAEs 
 Number (%) of subjects reporting any DLTs in Cycle 1 
 Number (%) of subjects reporting any serious TEAEs 
 Number (%) of subjects reporting any Grade 3 or Higher TEAEs 
 Number (%) of subjects reporting any TEAEs related to INCB054828 
 Number (%) of subjects reporting any TEAEs related to combination agent (for Part 3 
only) 
 Number (%) of subjects who temporarily interrupted INCB054828 due to TEAEs 
 Number (%) of subjects with INCB054828 dose reductions due to TEAEs  
 Number (%) of subjects who permanently discontinued INCB054828 due to TEAEs 
 Number (%) of subjects who withdrew from study due to TEAEs 
 Number (%) of subjects who had a fatal TEAE 
The following summaries will be produced by MedDRA term (if ≤ 10 subjects appear in a table, 
a listing may be appropriate): 
 Summary of TEAEs by SOC and PT 
 Summary of TEAEs by PT in decreasing order of frequency 
 Summary of TEAEs by SOC, PT, and maximum severity 
 Summary of Grade 3 or higher TEAEs by SOC and PT 
 Summary of Grade 3 or higher TEAEs by PT in decreasing order of frequency 
 Summary of INCB054828 treatment-related TEAEs by SOC and PT 
 Summary of INCB054828 treatment-related TEAEs by PT in decreasing order of 
frequency 
 Summary of INCB054828 treatment-related Grade 3 or higher TEAEs by PT in 
decreasing order of frequency 
 Summary of combination agent treatment-related TEAEs by SOC and PT 


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 Summary of combination agent treatment-related Grade 3 or higher TEAEs by SOC 
and PT 
 Summary of TEAEs with a fatal outcome by SOC and PT 
 Summary of serious TEAEs by SOC and PT 
 Summary of serious TEAEs by PT in decreasing order of frequency 
 Summary of INCB054828 treatment-related serious TEAEs by SOC and PT 
 Summary of TEAEs leading to INCB054828 dose interruption by SOC and PT 
 Summary of TEAEs leading to INCB054828 dose interruption by PT in decreasing 
order of frequency 
 Summary of TEAEs leading to INCB054828 dose reduction by SOC and PT 
 Summary of TEAEs leading to INCB054828 dose reduction by PT in decreasing 
order of frequency 
 Summary of TEAEs leading to discontinuation of INCB054828 by SOC and PT 
 Summary of TEAEs leading to discontinuation of INCB054828 by PT in decreasing 
order of frequency 
 Summary of TEAEs leading to withdrawal from the study by SOC and PT 
 Summary of TEAEs and Grade 3 or higher TEAEs by PT in decreasing order of 
frequency 
 Summary of INCB054828 treatment-related TEAEs and Grade 3 or higher TEAEs by 
PT in decreasing order of frequency 
 Summary of clinically notable TEAEs by category and PT 
 Summary of Grade 3 or higher clinically notable TEAEs by category and PT 
 Summary of clinically notable serious TEAEs by category and PT 
 Summary of clinically notable TEAEs leading to INCB054828 dose reduction by 
category and PT 
 Summary of clinically notable TEAEs leading to INCB054828 dose interruption by 
category and PT 
 Summary of clinically notable TEAEs leading to discontinuation of INCB054828 by 
category and PT 
 Summary of treatment-emergent nonserious TEAEs by SOC and PT 


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8.3. 
Clinical Laboratory Tests 
8.3.1. 
Laboratory Value Definitions 
For numeric laboratory results, the change and percentage change from baseline values will be 
summarized descriptively by visit.  Baseline will be determined according to Section 6.  If there 
are multiple values that meet the criteria for baseline, then the value from the central laboratory 
has priority over value from the local laboratory.  Thereafter, additional rules may be provided 
after consultation with the medical monitor to delineate which value will be defined as baseline. 
Laboratory test values outside the normal range will be assessed for severity based on CTCAE 
grade or similar criteria where clinical intervention is required for CTCAE grading.   
8.3.2. 
Laboratory Value Summaries 
Laboratory parameters identified in Table 2 will be summarized.  
Table 2: 
Laboratory Parameters to Be Summarized 
Panel 
Summary 
Serum chemistry 
Albumin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, 
bicarbonate, blood urea nitrogen, calcium, chloride, creatininea, direct bilirubin, 
glucose, lactate dehydrogenase, parathyroid hormonea, phosphatea, potassium, 
sodiuma, total bilirubin, total serum protein, uric acid, vitamin D (25-hydroxyvitamin 
 Da and 1,25-dihidroxyvitamin Da) 
Hematology 
Hematocrit, hemoglobin, platelet count, WBCs, red blood cells, basophils, 
eosinophils, lymphocytes, monocytes, neutrophils 
Coagulation  
PT, activated partial thromboplastin time, international normalized ratio  
Lipid 
Total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein 
Urinalysis  
pH and specific gravity 
a Line graph will be provided. 
All test results and associated normal ranges from central laboratories will be reported in SI 
units.  For numeric laboratory values, baseline value, postbaseline value, change from baseline, 
and percent change from baseline will be summarized by visit.  In addition, mean change from 
baseline will be plotted over time for selected laboratory parameters including but not limited to 
the following:  phosphate, sodium, calcium, 25-Hydroxyvitamin D, 1, 25-Dihydroxyvitamin D, 
parathyroid hormone, and creatinine. 
For the laboratory parameters that have CTCAE grading, shift tables will also be presented 
showing change in CTCAE severity grade from baseline to worst grade postbaseline.  Separate 
summaries for abnormally high and abnormally low laboratory values will be provided when the 
laboratory parameter has both high and low grading criteria.  The denominator for the percentage 
calculation will be the number of subjects in the baseline category. 
Categorical laboratory data will be tabulated by visit at baseline and postbaseline visits where 
appropriate. 


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8.4. 
Vital Signs 
Values at each scheduled visit, change, and percent change from baseline for vital signs, 
including systolic blood pressure, diastolic blood pressure, pulse, respiratory rate, body 
temperature, and body weight will be summarized descriptively. 
Criteria for clinically notable vital sign abnormalities are defined in Table 3.  The abnormal 
values for subjects exhibiting clinically notable vital sign abnormalities will be listed along with 
their assigned treatment group.  Alert vital signs are defined as an absolute value outside the 
defined range and percentage change from baseline greater than 25%.  The abnormal values for 
subjects exhibiting alert vital sign abnormalities will also be listed. 
Table 3: 
Criteria for Clinically Notable Vital Sign Abnormalities 
Parameter 
High Threshold 
Low Threshold 
Systolic blood pressure 
> 155 mmHg 
< 85 mmHg 
Diastolic blood pressure 
> 100 mmHg 
< 40 mmHg 
Pulse 
> 100 bpm 
< 45 bpm 
Temperature 
> 38ºC 
< 35.5ºC 
Respiratory rate 
> 24 breaths/min 
< 8 breaths/min 
8.5. 
Electrocardiograms 
Twelve-lead ECGs including heart rate, PR, QRS, QT, QTcF, and RR intervals will be obtained 
for each subject during the study.  Values at each scheduled visit, change, and percent change 
from baseline will be summarized for each ECG parameter.  Change and percent change from 
baseline will be calculated using the average of all nonmissing values before the first dose of 
study drug as the baseline value. 
Criteria for clinically notable ECG abnormalities are defined in Table 4.  The abnormal values 
for subjects exhibiting clinically notable ECG abnormalities will be listed.  Alert ECG are 
defined as an absolute value outside the defined range and percentage change greater than 25% 
(QRS 30%).  The abnormal values for subjects exhibiting alert ECG abnormalities will be listed. 
Table 4: 
Criteria for Clinically Notable Electrocardiogram Abnormalities 
Parameter 
High Threshold 
Low Threshold 
QTcF 
> 460 ms 
< 295 ms 
PR 
> 220 ms 
< 75 ms 
QRS 
> 120 ms 
< 50 ms 
QT 
> 500 ms 
< 300 ms 
RR 
> 1330 ms 
< 600 ms 
QTcF = Fridericia correction. 


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9. 
INTERIM ANALYSES 
No interim analysis is planned. 
10. 
CHANGES AND MODIFICATIONS TO THE ANALYSIS PLAN 
All versions of the SAP are listed in Table 5. 
Table 5: 
Statistical Analysis Plan Versions 
SAP Version 
Date 
Original 
13 APR 2017 
Amendment 1 
12 JUN 2019 
10.1. 
Changes to Protocol-Defined Analyses 
Not applicable. 
10.2. 
Changes to the Statistical Analysis Plan 
10.2.1. 
Amendment 1 
The original SAP has been updated to incorporate updates made to the study in Protocol 
Amendments 6, 7, and 8.  Specific changes include the following:  
• Sections 1, 2, and 3 (introduction, objectives and endpoints, and study design) to reflect 
the updates in Protocol Amendments 6, 7, and 8. 
• Section 5 was revised for consistency in treatment group definitions. 
• Section 6.1.2 was revised to reflect disease history that will be summarized. 
• Section 6.4 was revised to reflect accurate exposure summaries. 
• Sections 7 and 8 were updated to align with updated lists of planned tables, figures, and 
listings. 
• Appendix C was revised to update the list of planned tables, figures, and listings and to 
remove the sample data displays, as they will be included in a separate document. 


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11. 
REFERENCES 
Brookmeyer R, Crowley J. A confidence interval for the median survival time. Biometrics 1982; 
38:29-41. 
Durie BGM, Harousseau JL, Miguel JS, et al. International uniform response criteria for multiple 
myeloma. Leukemia 2006;20:1467-1473. 
Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumors: 
Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-247. 
Food and Drug Administration. Guidance for Industry: Clinical Trial Endpoints for the Approval 
of Cancer Drugs and Biologics. 2018. https://www.fda.gov/downloads/Drugs/ 
GuidanceComplianceRegulatoryInformation/Guidances/UCM071590.pdf. Accessed 
June 3, 2019. 
Mosteller RD. Simplified calculation of body surface area. N Engl J Med 1987;317:1098. 


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Appendix A. 
RESPONSE ASSESSMENT CRITERIA FOR MULTIPLE 
MYELOMA 
 


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Source:  Durie et al 2006.  


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APPENDIX B. RESPONSE ASSESSMENT CRITERIA FOR SUBJECTS 
WITH MYELOPROLIFERATIVE NEOPLASMS 
Response Criteria for Myeloproliferative Neoplasms With Genetic Alterations in FGF or 
FGFR Genes 
Complete Response 
Criteria 
Hematologic 
Durable peripheral blood count remission, defined as:  absence of circulating blasts, 
hemoglobin ≥ 100 g/L and < ULN, platelet count ≥ 100 × 109/L and < ULN, WBC and 
neutrophil count within institutional normal range. 
For subjects with baseline eosinophilia:  eosinophils < 1.5 × 109/L. 
Bone marrow 
Cellularity appropriate for age, resolution of abnormal morphology, blasts ≤ 5%. 
Spleen 
For subjects with splenomegaly at baseline:  < 25% increase in spleen size by palpation 
or imaging if baseline spleen is < 10 cm or < 50% if baseline spleen is ≥ 10 cm. 
Lymph nodes 
For subjects with lymph node disease:  target nodes/nodal masses must regress to ≤ 
1.5 cm in longest transverse diameter of lesion, no extralymphatic sites of disease, no new 
lesions present.  Must be PET negative, if positive at baseline. 
Cytogenetic CR 
Meets above criteria and MPN-associated cytogenetic abnormalities are no longer 
detected (requires that abnormalities were found at baseline). 
Molecular CR 
Meets above criteria and MPN-associated molecular abnormalities (eg, by PCR) are no 
longer detected (requires that abnormalities were found at baseline) 
Partial Response  
Criteria 
Hematologic 
Hemoglobin ≥ 100 g/L and < ULN, 50% reduction in WBC and neutrophil count, 50% 
reduction in circulating blasts.  
For subjects with eosinophilia:  > 50% reduction in eosinophil count. 
Bone marrow 
> 50% reduction in blasts. 
Spleen 
For subjects with splenomegaly:  < 25% increase in spleen size by palpation or imaging if 
baseline spleen is < 10 cm or < 50% if baseline spleen is ≥ 10 cm. 
Lymph nodes 
For subjects with lymph node disease:  ≥ 50% decrease in the sum of the product of the 
perpendicular diameters of up to 6 target measureable nodes and extranodal sites, no new 
lesions present. 
Cytogenetics 
No new abnormalities detected. 
Molecular markers 
No new abnormalities detected. 
Stable Disease 
Criteria 
Stable disease 
Failure to achieve at least Partial Remission, but no evidence of progression for at least 
9 weeks. 
Progressive Disease 
Criteria 
Hematologic  
WBC:  > 2 times increase compared with baseline count in the absence of a concurrent 
acute or subacute medical illness. 
For subjects with circulating blasts:  ≥ 50% increase in circulating blasts. 
Bone marrow 
≥ 50% increase in blasts. 
Spleen 
For subjects with splenomegaly:  > 25% increase in spleen size by palpation or imaging if 
baseline spleen is < 10 cm and > 50% if baseline spleen is ≥ 10 cm or appearance of new 
splenomegaly. 
Lymph nodes 
If lymph node disease is present:  a single node must be abnormal with the longest 
transverse diameter > 1.5 cm and  ≥ 50% increase in the sum of measureable lesions or 
new or clear progression of preexisting nonmeasured lesions. 
CR = complete response; MPN = myeloproliferative neoplasm; PCR = polymerase chain reaction; PET = positron emission 
tomography; ULN = upper limit of normal; WBC = white blood cell. 


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APPENDIX C. PLANNED TABLES, FIGURES, AND LISTINGS 
This appendix provides a list of the planned tables, figures, and listings for the CSR.  Standard 
tables will follow the conventions in the Standard Safety Tables initial version.  Shells are 
provided for nonstandard tables in a separate document. 
The lists of tables, figures, listings and the shells are to be used as guideline.  Modifications of 
the list or shells that do not otherwise affect the nature of the analysis will not warrant an 
amendment to the SAP. 
For each baseline and demographic characteristics, safety, laboratory, vital sign, and ECG table 
and figure listed below, 2 sets of tables and figures will be produced:  Part 1 and Part 2 combined 
and Part 3a and Part 3b combined.  For each efficacy table listed below, 2 sets of tables will be 
produced:  Part 2 and Part 3b.  For each listing listed below, 4 sets of listings will be produced 
for Part 1, Part 2, Part 3a, and Part 3b. 
Tables 
Table No. 
Title 
Population Standard 
In-Text 
Baseline and Demographic Characteristics 
1.1.1 
Analysis Populations 
All Enrolled 
X 
 
1.1.2 
Summary of Subject Disposition 
Efficacy 
X 
X 
1.1.3 
Summary of Number of Subjects Enrolled by Country and Site 
Efficacy 
X 
 
1.1.4 
Summary of Protocol Deviations 
Efficacy 
X 
 
1.2.1 
Summary of Demographics and Baseline Characteristics 
Efficacy 
X 
X 
1.2.2 
Summary of Disease History 
Efficacy 
X 
X 
1.2.3 
Summary of Prior Cancer Therapy 
Efficacy 
X 
X 
1.3 
Summary of Medical History 
Efficacy 
X 
 
1.4.1 
Summary of Prior Medications 
Efficacy 
X 
 
1.4.2 
Summary of Concomitant Medications 
Efficacy 
X 
 
Efficacy 
2.1 
Summary of Best Overall Response and Overall Response 
Rate 
Efficacy 
 
X 
 
 
 
 
 
 
 
 
 
 
2.2.3 
Summary of Best Change in Target Lesion Size 
Efficacy 
 
X 
2.3.1 
Summary of ECOG Performance Status 
Efficacy 
X 
 
Safety 
3.1.1 
Summary of Study Drug Exposure 
Safety 
X 
X 
3.1.2 
Summary of Study Drug Compliance 
Safety 
X 
X 
3.2.1 
Overall Summary of Treatment-Emergent Adverse Events 
Safety 
X 
X 
3.2.2 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term 
Safety 
X 
X 
3.2.3 
Summary of Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
X 
3.2.4 
Summary of Treatment-Emergent Adverse Events by 
MedDRA System Organ Class, Preferred Term, and 
Maximum Severity 
Safety 
X 
 


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Table No. 
Title 
Population Standard 
In-Text 
3.2.5 
Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by MedDRA System Organ Class and Preferred Term 
Safety 
X 
X 
3.2.6 
Summary of Grade 3 or Higher Treatment-Emergent Adverse 
Events by MedDRA Preferred Term in Decreasing Order of 
Frequency 
Safety 
X 
X 
3.2.7 
Summary of INCB054828 Treatment-Related Treatment-
Emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
 
3.2.8 
Summary of INCB054828 Treatment- Related Treatment-
Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety 
X 
X 
3.2.9 
Summary of INCB054828 Treatment-Related Grade 3 or 
Higher Treatment-Emergent Adverse Events by MedDRA 
System Organ Class and Preferred Term 
Safety 
X 
 
3.2.10 
Summary of Combination Agent Treatment-Related 
Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term 
Safety 
X 
 
3.2.11 
Summary of Combination Agent Treatment-Related Grade 3 
or Higher Adverse Events by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
 
3.2.12 
Summary of Treatment-Emergent Adverse Events With a 
Fatal Outcome by MedDRA System Organ Class and 
Preferred Term  
Safety 
X 
 
3.2.13 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA System Organ Class and Preferred Term  
Safety 
X 
X 
3.2.14 
Summary of Serious Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
X 
 
3.2.15 
Summary of INCB054828 Treatment-Related Serious 
Treatment-Emergent Adverse Events by MedDRA System 
Organ Class and Preferred Term  
Safety 
X 
X 
3.2.16 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB054828 Dose Interruption by MedDRA System Organ 
Class and Preferred Term  
Safety 
X 
 
3.2.17 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB054828 Dose Interruption by MedDRA Preferred Term 
in Decreasing Order of Frequency 
Safety 
X 
 
3.2.18 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB054828 Dose Reduction by MedDRA System Organ 
Class and Preferred Term  
Safety 
X 
 
3.2.19 
Summary of Treatment-Emergent Adverse Events Leading to 
INCB054828 Dose Reduction by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety 
X 
 
3.2.20 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of INCB054828 by MedDRA System Organ 
Class and Preferred Term  
Safety 
X 
 
3.2.21 
Summary of Treatment-Emergent Adverse Events Leading to 
Discontinuation of INCB054828 by MedDRA Preferred Term 
in Decreasing Order of Frequency 
Safety 
X 
 


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Table No. 
Title 
Population Standard 
In-Text 
3.2.22 
Summary of Treatment-Emergent Adverse Events Leading to 
Withdrawal From the Study by MedDRA System Organ Class 
and Preferred Term  
Safety 
X 
 
3.2.23 
Summary of Treatment-Emergent Adverse Events and 
Grade 3 or Higher Treatment-Emergent Adverse Events by 
MedDRA Preferred Term in Decreasing Order of Frequency 
Safety 
 
 
3.2.24 
Summary of INCB054828 Treatment-Related Treatment-
Emergent Adverse Events and Grade 3 or Higher Treatment-
Emergent Adverse Events by MedDRA Preferred Term in 
Decreasing Order of Frequency 
Safety 
 
 
3.2.25 
Summary of Clinically Notable Treatment-Emergent Adverse 
Events by Category and Preferred Term 
Safety 
 
 
3.2.26 
Summary of Grade 3 or Higher Clinically Notable Treatment-
Emergent Adverse Events by Category and PT 
Safety 
 
 
3.2.27 
Summary of Clinically Notable Serious Treatment-Emergent 
Adverse Events by Category and Preferred Term 
Safety 
 
 
3.2.28 
Summary of Clinically Notable Treatment-Emergent Adverse 
Events Leading to INCB054828 Dose Reduction by Category 
and Preferred Term 
Safety 
 
 
3.2.29 
Summary of Clinically Notable Treatment-Emergent Adverse 
Events Leading to INCB054828 Dose Interruption by 
Category and Preferred Term 
Safety 
 
 
3.2.30 
Summary of  Clinically Notable Treatment-Emergent Adverse 
Events Leading to Discontinuation of INCB054828 by 
Category and Preferred Term 
Safety 
 
 
3.2.31 
Summary of Treatment-Emergent Nonserious Treatment-
Emergent Adverse Events by MedDRA System Organ Class 
and Preferred Term 
Safety 
X 
X 
Laboratory 
3.3.1 
Summary of Laboratory Values - Hematology 
Safety 
X 
 
3.3.2  
Shift Summary of Hematology Values in CTC Grade - to the 
Worst Abnormal Value  
Safety 
X 
 
3.3.3 
Summary of Treatment-Emergent Worsening of Laboratory 
Abnormalities - Hematology 
Safety 
X 
 
3.3.4 
Summary of Laboratory Values - Chemistry 
Safety 
X 
 
3.3.5 
Shift Summary of Chemistry Values in CTC Grade - to the 
Worst Abnormal Value  
Safety 
X 
 
3.3.6 
Summary of Treatment-Emergent Worsening of Laboratory 
Abnormalities – Chemistry 
Safety 
X 
 
3.3.7 
Summary of Laboratory Values - Coagulation 
Safety 
X 
 
3.3.8 
Shift Summary of Coagulation Values in CTC Grade - to the 
Worst Abnormal Value  
Safety 
X 
 
3.3.9 
Summary of Treatment-Emergent Worsening of Laboratory 
Abnormalities - Coagulation 
Safety 
X 
 
3.3.10 
Summary of Laboratory Values - Urinalysis 
Safety 
X 
 
Vital Signs 
3.4.1 
Summary of Systolic Blood Pressure 
Safety 
X 
 
3.4.2 
Summary of Diastolic Blood Pressure  
Safety 
X 
 
3.4.3 
Summary of Pulse  
Safety 
X 
 


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INCB 54828-101 SAP Amendment 1 
12 JUN 2019 
Table No. 
Title 
Population Standard 
In-Text 
3.4.4 
Summary of Body Temperature 
Safety 
X 
 
3.4.5 
Summary of Respiratory Rate 
Safety 
X 
 
3.4.6 
Summary of Body Weight 
Safety 
X 
 
ECG 
3.5.1 
Summary of RR Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.2 
Summary of PR Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.3 
Summary of QRS Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.4 
Summary of QT Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.5 
Summary of QTcF Interval (ms) From 12-Lead ECG 
Safety 
X 
 
3.5.6 
Summary of Heart Rate (bpm) From 12-Lead ECG 
Safety 
X 
 
3.5.7 
Summary of Outliers of QT, QTcB, and QTcF Interval Values 
(ms) From 12-Lead ECG 
Safety 
X 
 
3.5.8 
Summary of Clinically Significant ECG Abnormalities 
Safety 
X 
 
Figures 
Figure No. 
Title 
 
 
 
  
4.2.3 
Waterfall Plot of Best Percent Change of Target Lesion Size From Baseline (Efficacy)  
4.6 
Line Graph of Mean Change From Baseline for Selected Laboratory Values (Safety) 
Listings 
Listing No. 
Title 
2.1.1 
Analysis Populations 
2.1.2 
Subject Enrollment and Disposition Status 
2.1.3 
Subject Inclusion and Exclusion Criteria 
2.2 
Protocol Deviations 
2.4.1 
Demographic and Baseline Characteristics 
2.4.2 
Oncology Disease History 
2.4.3 
FGF and FGFR Status 
2.4.4 
Prior Systemic Therapy 
2.4.5 
Prior Surgery 
2.4.6 
Prior Radiotherapy 
2.4.7 
Medical History 
2.4.8 
Prior and Concomitant Medications 
2.5 
Study Drug Compliance 
2.6.1 
Best Overall Response,
  
2.6.2 
Investigator-Reported Assessment by RECIST v1.1 
2.6.3 
Response Assessment: Target Lesions 
2.6.4 
Response Assessment: Non-Target Lesions 
2.6.5 
Response Assessment: New Lesions 
2.6.6 
Investigator Reported Assessment for Myeloma 
2.6.7 
Investigator Reported Assessment for MPN 
2.6.8 
Bone Marrow Testing Results 


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Page 38 of 38 
INCB 54828-101 SAP Amendment 1 
12 JUN 2019 
Listing No. 
Title 
2.6.9 
Flow Cytometry Results 
2.6.10 
Tumor Tissue 
2.6.11 
ECOG Status 
2.7.1 
Study Drug Administration 
2.7.3 
Adverse Events  
2.7.4 
Dose-Limiting Toxicities 
2.7.5 
INCB054828 Treatment-Related Adverse Events 
2.7.6 
Adverse Events Leading to Interruption, Reduction, or Discontinuation of INCB054828 
2.7.7 
Adverse Events Leading to Discontinuation of INCB054828 
2.7.8 
Serious Adverse Events 
2.7.9 
Adverse Events Leading to Death 
2.7.10 
Adverse Events Leading to Withdrawal From Study 
2.7.11 
Clinically Notable Adverse Events 
2.8.1.1 
Clinical Laboratory Values - Hematology 
2.8.1.2 
Clinical Laboratory Values - Chemistry 
2.8.1.3 
Clinical Laboratory Values - Coagulation 
2.8.1.4 
Clinical Laboratory Values - Urinalysis 
2.8.2.1 
Abnormal Clinical Laboratory Values - Hematology 
2.8.2.2 
Abnormal Clinical Laboratory Values - Chemistry 
2.8.2.3 
Abnormal Clinical Laboratory Values - Coagulation 
2.8.2.4 
Abnormal Clinical Laboratory Values - Urinalysis 
2.8.3 
PK Blood Sampling Times 
2.8.4 
PK Urine Sampling Times 
2.9.1 
Vital Signs 
2.9.2 
Abnormal Vital Sign Values 
2.9.3 
Alert Vital Sign Values 
2.10.1 
12-Lead ECG Values 
2.10.2 
Abnormal 12-Lead ECG Values 
2.10.3 
Alert 12-Lead ECG Values 
2.11.1 
Eye Examinations 
2.11.2 
Skeletal Examinations