MATCH Treatment Subprotocol Z1I: Phase II Study of AZD1775 in Patients With Tumors Containing BRCA1 and BRCA2 Mutations
Phase: PHASE2
Conditions: Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Hematopoietic and Lymphoid Cell Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm, Refractory Multiple Myeloma
Sponsor: National Cancer Institute (NCI)

i 
28 State Street, Suite 1100, Boston, MA 02109 
p: 857.504.2900 
f: 617. 589.0914 
ecog-acrin.org 
July 10, 2019 
Martha Kruhm, MS RAC 
Head, Protocol and Information Office 
Quality Assurance Section 
CTEP, DCT, NCI 
6130 Executive Blvd, EPN Room 7000 
Bethesda, MD   20892 
Dear Ms. Kruhm: 
Enclosed is Addendum #21 to EAY131-Z1I, Phase II Study of AZD1775 in Patients with Tumors 
Containing BRCA1 and BRCA2 Mutations.  
Please replace your current copy of the protocol and Informed Consent document (if ICD 
changed) with this (these) updated version(s).  We recommend that each institution maintain a 
file containing the original protocol, Informed Consent, and all subsequent revisions/versions. 
IRB Review Requirements: 
This addendum has been reviewed and approved by the Central IRB which is the sole 
IRB of record for this study. 
Implementation of this addendum must occur on the activation date. Sites are not 
permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 
after the activation date of this addendum.] 
This addendum is in response to Dr. Charles Kunos’s June 19, 2019 Request for Rapid 
Amendment for AZD1775 (adavosertib). 
The following revisions to EAY131-Z1I protocol have been made in this addendum: 
Section 
Change 
1. 
Cover Page 
Updated Version date. 
2. 
3.3 
Updated the AZD1775 (adavosertib) CAEPR list with version 2.6, May 14, 
2019. 
The following revisions to EAY131-Z1I Informed Consent Document have been made in this 
addendum: 
Section 
Change 
1. 
Page 1 
Updated Version Date. 
2. 
What possible risks can I 
expect from taking part 
in this study? 
Updated the AZD1775 (adavosertib) possible risks risk list with version 
2.6 May 14, 2019. 
If you have any questions regarding this addendum, please contact aagu@ecog-acrin.org or 
857-504-2900.

ii 
We request review and approval of this addendum to EAY131-Z1I so ECOG-ACRIN may 
activate it promptly.   
Thank you.  
Sincerely, 
Pamela Cogliano 
Senior Director of Protocol Development 
Enclosure 
 
CC: Shivaani Kummar, MD 
Kim A. Reiss Binder, MD 
James M. Ford, MD 
Alice Chen, MD 
Keith Thomas Flaherty, MD 
Lyndsay N. Harris. MD 
Peter O’Dwyer, MD 
Mickey Williams, PhD 
James V. Tricoli, PhD 
Stanley Hamilton, MD 
Lisa McShane, PhD  
Larry Rubinstein, PhD 
Robert Gray, PhD 
Shuli Li, PhD 
Lalitha Shankar, MD 
Susanna Lee, MD, PhD 
Constantine Gastonis, PhD 
Paolo Caimi, MD 
Shaji Kumar, MD 
Carlos Arteaga, MD 
Edith Mitchell, MD 
John J. Wright, MD, PhD 
Bruce Giantonio, MD 
Donna Marinucci 
Kerry Higgins 
Gayle Ipock 
Jean MacDonald 
Carol Chami, R.N. 
Juanita Andrews 
Melinda Flood 
Kelly Redmond 
Becky Fillingham 
Kevin Pollard 
Abuchi Agu 
Elanna Radomyshelsky 
Camilla Abreu  
Michael T. Balco 
Lauren Lambert 
Cayden Maican 
Margaret Cavenagh 
Ben Kim 
Alexandra Sachs 
 
 
 

EAY131-Z1I 
1 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1I: Phase II Study of 
AZD1775 in Patients with Tumors Containing BRCA1 and 
BRCA2 Mutations 
AZD1775 TREATMENT SUBPROTOCOL CHAIR: Shivaani Kummar, MD 
AZD1775 TREATMENT SUBPROTOCOL CO-
CHAIR: 
Kim A. Reiss Binder, MD 
AZD1775 TRANSLATIONAL CHAIR: James M. Ford, MD 
Version Date: July 10, 2019 
NOTE: This subprotocol (EAY131-Z1I) should 
be used in conjunction with the 
MATCH Master Protocol (EAY131). 
SUBPROTOCOL ACTIVATION DATE 
March 13, 2017 (Incorporated in Addendum #7) 
Addendum #13 
Addendum #14 
Addendum #17 
Addendum #21 
Agent 
 
NSC# 
Supply 
AZD1775 
 
751084 
NCI Supplied 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
2 
Table of Contents 
Schema ............................................................................................................. 4 
1. Introduction ................................................................................................ 5 
1.1 
AZD1775 ............................................................................................ 5 
1.2 
Supporting Preliminary Data ............................................................... 6 
2. Selection of Patients .................................................................................... 9 
2.1 
Registration to Treatment ................................................................... 9 
3. AZD1775 Treatment Plan ........................................................................... 11 
3.1 
Administration Schedule ................................................................... 11 
3.2 
Adverse Event Reporting Requirements ............................................. 11 
3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for 
AZD1775 (MK-1775, NSC 751084) ...................................................... 14 
3.4 
Dose Modifications ........................................................................... 18 
3.5 
Supportive Care ................................................................................ 19 
3.6 
Duration of Agent-Specific Treatment ................................................ 20 
3.7 
Duration of Follow-Up ...................................................................... 20 
4. Study Parameters ...................................................................................... 21 
4.1 
Therapeutic Parameters for AZD1775 Treatment................................ 21 
5. Drug Formulation and Procurement ........................................................... 23 
5.1 
AZD1775 (NSC 751084) ..................................................................... 24 
6. Translational Studies.................................................................................. 26 
7. References ................................................................................................ 26 
Appendix I  Patient Pill Calendar ....................................................................... 27 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-Z1I ......................... 30 
Appendix III  Patient Drug Information Handout and Wallet Card ....................... 34 
Appendix IV  Patient Handout for Management of Diarrhea ............................... 36 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
3 
 
TREATMENT SUBPROTOCOL CHAIR 
Shivaani Kummar, MD 
Stanford University School of Medicine 
780 Welch Road, Rm CJ250L 
Palo Alto, CA 94304 
Phone #: (650) 724-9084 
Fax #: (650) 721-1265 
E-mail: skummar@stanford.edu 
 
 
TREATMENT SUBPROTOCOL CO-CHAIR  
Kim A. Reiss Binder, MD 
Hospital of the University of Pennsylvania 
3400 Civic Center Boulevard 
South Pavilion Ten Floor, Room 107 
Philadelphia, PA 19104 
Phone #: (215) 360-0735 
Fax #: (215) 662-4646 
E-mail: Kim.ReissBinder@uphs.upenn.edu 
 
 
TRANSLATIONAL CHAIR 
James M. Ford, MD 
Stanford University School of Medicine 
300 Pasteur Drive 
Stanford, CA 94305 
Phone #: (650) 723-7621 
Fax #: (650) 725-9113 
E-mail: jmf@stanford.edu 
 
 
 
 
 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
4 
Schema 
Long-Term Follow-Up
AZD1775, 300mg PO daily for 5 
days on 2 days off, 2 weeks on 1 
week off, every 21 day cycle
Until progression or unacceptable 
toxicity
Cycle = 21 days
Accrual Goal: 35
 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
5 
1. Introduction 
1.1 
AZD1775 
Cell cycle regulation depends on a delicate balance between cyclins and cyclin-
dependent kinases (Cdks) that allow for progression through the cell cycle, and 
Cdk inhibitors that halt progression in the setting of DNA damage. DNA 
replication during S phase generates intermediate DNA structures that are 
vulnerable to genotoxic insults. In addition, oncogenes can induce lesions at 
replication forks, further exacerbating genomic instability. In response to DNA 
damage, surveillance protein complexes such as Mre11/Rad50-Nbs1 complex 
and Rad9/Rad1/Hus1 complex recruit repair proteins and halts cell cycle 
progression, allowing time for DNA repair. Ataxia-telangectasia mutated (ATM) 
protein kinase and ataxia-telangectasia-related (ATR) protein kinase, two 
members of the phosphatidyl inositol 3-kinase-like kinase (PIKK) family, are 
central to the DNA damage repair process. Depending on the type of genotoxic 
stress, either ATM or ATR is preferentially activated1. ATM is primarily activated 
in response to double-stranded DNA breaks, while ATR is activated by a broader 
spectrum of genotoxic stimuli and primarily activated in response to single-strand 
DNA breaks. 
ATM/ATR kinases regulate cell cycle checkpoints by phosphorylation of multiple 
downstream proteins, including proteins associated with the recognition of 
double-stranded DNA breaks such histone H2AX, proteins involved in the 
assembly of protein complexes at the site of DNA damage, and effector kinases 
such as checkpoint kinase 1/2 (Chk1) and (Chk2). In contrast to Chk2, Chk1 can 
be activated by both ATM and ATR, and activation can occur during normal cell 
cycle progression or in response to replicative stress. Activated Chk1 in turn 
concomitantly phosphorylates Wee1 and Cdc25C, thereby activating Wee1 
kinase activity and inactivating Cdc25C phosphatase activity. Wee1 is a tyrosine 
kinase implicated in the inhibitory phosphorylation of CDK1/CDC2-bound cyclin B 
complex responsible for G2 arrest. Originally identified in fission yeast, wee 1 
deficiency resulted in premature mitotic entry and replication of smaller-sized 
yeast. Wee1 belongs to a family of protein kinases involved in the terminal 
phosphorylation and inactivation of (CDK1/CDC2)-bound cyclin B via 
phosphorylation of its Tyr15 residue near the ATP-binding pocket, resulting in G2 
cell cycle arrest in response to DNA damage. Wee1 overexpression has been 
demonstrated in hepatocellular carcinoma, luminal and HER-2 positive breast 
cancers, colon, lung carcinoma, and seminoma tumor samples. 
AZD1775, 2-allyl-1-[6-(1-hydroxy-1-methyl-ethyl)-2-pyridyl]-6-[4- 
(4-methylpiperazin-1-yl)anilino]pyrazolo[3,4-d]pyrimidin-3-one hemihydrate, is a 
selective, adenosine-triphosphate (ATP) competitive, small molecule inhibitor of 
Wee1 kinase (IC50 = 5.18nM), that directly inhibits phosphorylation of CDC2 at 
Tyr15. A comprehensive review of AZD1775 can be found in the AZD1775 
Investigator's Brochure. 
AZD1775 has been shown to inhibit phosphorylated CDC2 in p53 mutant WiDr 
colon and lung carcinoma cells, as measured by colorimetric ELISA in a dose-
dependent manner [Figure 1A]. Additionally, premature mitotic entry was 
demonstrated by concomitant increase in the percentage of cells expressing 
phosphorylated histone H3 at the same doses [Figure 1B].   
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
6 
Figure 1A 
Figure 1B 
 
In in vitro studies, AZD1775 inhibits WEE1 activity and induces DNA 
damage as well as G2/M checkpoint escape in cell-based assays. AZD1775 
increases cytotoxicity when used in combination with DNA damaging agents, 
such as gemcitabine, cisplatin, carboplatin, and topotecan, in p53-deficient cell 
lines. In in vivo studies, AZD1775 was well tolerated and showed enhancement 
of anti-tumor efficacy by gemcitabine, carboplatin, cisplatin, 5-fluorouracil (5-FU), 
and capecitabine in nude rat xenograft tumor models. Similarly, in nude mouse 
xenograft models, AZD1775 treatment resulted in significant tumor growth 
inhibition at tolerated doses, and also enhanced the anti-tumor growth effect of 
gemcitabine, carboplatin, radiation therapy, and olaparib, a PARP inhibitor that 
also induces replication associated DNA damage. Moreover, in preclinical cancer 
cell models associated with high levels of endogenous replication stress resulting 
from a combination of G1/S checkpoint deficiencies due to p53 mutations or 
CDKN2A deletions and the over-expression of oncogenic drivers such as MYC, 
mutant KRAS or the amplification of Cyclin E, AZD1775 also demonstrated 
significant single-agent anti-tumor activity. 
1.2 
Supporting Preliminary Data  
As of 11 November 2016, a total of approximately 551 patients have been 
exposed to AZD1775 in AstraZeneca-sponsored or Merck-sponsored clinical 
studies. In addition, approximately 350 patients have also received AZD1775 as 
part of externally-sponsored scientific research. These patients have received 
single doses per cycle as high as 1300 mg of AZD1775 as monotherapy, 325 mg 
of AZD1775 in a single-dose in combination with chemotherapy, and 325 mg 
twice a day (BID) in a multiple-dose regimen in combination with chemotherapy. 
The PK data of AZD1775 following a single oral administration showed a 
moderate rate of absorption with a Tmax occurring at 3 to 4 hours. Post-peak 
plasma concentrations declined essentially in a mono-exponential manner with a 
t1/2 in the region of 10 hours. Exposure as measured by maximum plasma drug 
concentration observed (Cmax) and AUC0-∞ increased in a dose-proportional 
manner over the dose range of 325 to 1300 mg. 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
7 
Based on the safety data from the completed AZD1775 clinical studies and 
preliminary data from ongoing studies adverse drug reactions to AZD1775 
monotherapy include: anemia, neutropenia, thrombocytopenia, QTc prolongation, 
gastrointestinal events such as dyspepsia, diarrhea, nausea and vomiting (with 
or without dehydration or serum electrolyte decreases), as well as decreased 
appetite. 
Based on information emerging during the clinical development program of 
AZD1775, potential risks with AZD1775 monotherapy include asthenia/fatigue, 
febrile neutropenia, gastrointestinal hemorrhage, lymphopenia/lymphocyte count 
decreased, leukopenia/WBC count decreased, myalgia, stomatitis, sepsis and 
transaminases elevation. 
Based on the safety data from the 6 completed clinical studies and preliminary 
data from ongoing studies, the following have been determined to be important 
identified and/or potential risks, and should be closely monitored: blood and 
lymphatic disorders (anaemia, neutropenia, thrombocytopenia, leukopenia, 
lymphopenia, febrile neutropenia, pancytopenia), gastrointestinal disorders 
(diarrhoea, vomiting, nausea), and cardiac disorders (tachycardia, palpitations, 
QTc prolongation). Gastrointestinal haemorrhage is also included as an 
important potential risk. 
The inhibition of WEE1 results in perpetually active CDK-1-Cyclin-B, leading to 
dysregulation of the G2 checkpoint and ongoing cell mitosis despite aberrancies 
in the DNA. Cells deficient in HR repair secondary to mutations in the BRCA 
genes have defective DNA damage repair. Inhibition of WEE 1 kinase in such 
cells would result in a higher fraction of cells with defective DNA entering mitosis, 
eventually leading to apoptosis. This was demonstrated in the single agent trial of 
AZD1775 in patients with advanced solid tumors2. Nine patients with BRCA1/2 
mutations were enrolled in this study, 2 in the escalation phase and 7 in the 
BRCA expansion cohort. Confirmed partial responses were observed in two 
patients with germline BRCA1 mutations, one with a deletion in exon 15 and 
another with a mutation in the coding region of exon 11 (C3508G). [Figure 2] 
Figure 2: Clinical responses in patients carrying BRCA mutations enrolled on the 
single agent AZD1775 study 
  
In order to evaluate for the pharmacodynamics effects of the tumor, six patients 
were enrolled in the expansion cohort with paired tumor biopsies obtained at 
38.8
28.2
-7
-14
-23.2-23.5
-37.5-38.5
-50
-40
-30
-20
-10
0
10
20
30
40
50
Best Response on Study
in Patients with BRCA1/2 
mutations

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
8 
baseline and 2 to 5 hours after the fifth dose of the first week of administration of 
drug. Five of 6 paired tumor biopsies showed adequate tumor content and were 
considered analyzable for pharmacodynamic endpoints. Dramatic reductions in 
pY15-Cdk levels (84% and 90% compared to baseline) were found in 2 of 5 
paired tumor biopsies with 3 of the 5 patients also demonstrating concurrent 
evidence of DNA damage response based on increased levels of γH2AX [Figure 
3]. We were unable to detect a decrease in pY15-Cdk for one patient specimen 
due to low expression of pY15-Cdk at baseline. One patient with KRAS-mutant 
non-squamous non-small cell lung cancer (NSCLC) with TP53 mutation on 
archival tissue had a concurrent increase in pHH3 level as well as γH2AX level 
on post-treatment tumor biopsy[Figure 3]. 
 
Figure 3: Reduction in pY15-Cdk and concurrent increase in gH2AX signaling 
and pHH3 by AZD1775 in paired tumor biopsies: Immunofluorescence assay for 
pY15-Cdk (phosphorylated Tyr15-Cdk), γH2AX (phosphorylated histone H2AX), 
and pHH3 (phosphorylated histone H3) in paired tumor biopsies from a patient 
with nonsquamous non–small-cell lung carcinoma. Post-treatment biopsies were 
obtained 2 to 5 hours after the fifth dose on day 3 of cycle 1. Hematoxylin and 
eosin staining demonstrates adequate tumor content. A decrease in pY15-Cdk 
signal in the post-treatment biopsy is consistent with the downstream effect of 
Wee1 inhibition. Increases in γH2AX and pHH3 levels were observed in the post-
treatment biopsy. (A) Hematoxylin and eosin, (B) pY15-Cdk, (C) γH2AX, and (D) 
pHH3. 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
9 
2. Selection of Patients 
Each of the criteria in the checklist that follows must be met, along with the eligibility in 
the MATCH Master Protocol, in order for a patient to be considered eligible for this 
study. Use the checklist to confirm a patient’s eligibility. For each patient, this checklist 
must be photocopied, completed and maintained in the patient’s chart.  
In calculating days of tests and measurements, the day a test or measurement is 
done is considered Day 0. Therefore, if a test is done on a Monday, the Monday 
four weeks later would be considered Day 28.  
ECOG-ACRIN Patient No. ____________________________ 
Patient’s Initials (L, F, M) _______________________ 
Physician Signature and Date ___________________ 
NOTE: 
Policy does not allow for the issuance of waivers to any protocol specified 
criteria (http://ctep.cancer.gov/protocolDevelopment/policies_deviations.htm). 
Therefore, all eligibility criteria listed in Section 2 must be met, without 
exception. The registration of individuals who do not meet all criteria listed in 
Section 2 can result in the participant being censored from the analysis of the 
study, and the citation of a major protocol violation during an audit.  All 
questions regarding clarification of eligibility criteria must be directed to the 
Group's Executive Officer (EA.Execofficer@jimmy.harvard.edu) or the 
Group's Regulatory Officer (EA.RegOfficer@jimmy.harvard.edu). 
NOTE: 
Institutions may use the eligibility checklist as source documentation if it has 
been reviewed, signed, and dated prior to registration/randomization by the 
treating physician. 
NOTE: 
All patients must have signed the relevant treatment consent form 
2.1 
Registration to Treatment  
2.1.1 
Patients must fulfill all eligibility criteria outlined in Section 3.1 of 
MATCH Master Protocol (excluding Section 3.1.6) at the time of 
registration to treatment step (Step 1, 3, 5, 7). 
2.1.2 
Patients must have mutation in the BRCA1 or BRCA2 gene in the 
tumor, or another aberration, as determined via the MATCH Master 
Protocol and according to Appendix II. See Appendix II for information 
on the targeted mutations and corresponding Levels of Evidence. 
Patients with tumor carrying mutations defined as variants of 
uncertain significance will not qualify. 
2.1.3 
Patients with ovarian cancer or HER2 negative, metastatic breast 
cancer must have received a PARP inhibitor as part of or as one of 
their prior lines of therapy.  
2.1.4 
Patients must have an electrocardiogram (ECG) within 8 weeks prior 
to treatment assignment and must have no clinically important 
abnormalities in rhythm, conduction or morphology of resting ECG 
(e.g. complete left bundle branch block, third degree heart block). 
Date of ECG:  _______________ 
_____
_____
_____ 
_____
Rev. Add13 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
10 
2.1.5 
Patients must not have known hypersensitivity to AZD1775 or 
compounds of similar chemical or biologic composition. 
2.1.6 
Patients receiving any medications or substances that are inhibitors or 
inducers of CYP3A4, or CYP3A4 substrates need to be reviewed by 
the study investigator (Appendix VI MATCH Master Protocol). 
Continuation of such medications will be at the discretion of the study 
investigator. Concomitant use of aprepitant and fosaprepitant is 
prohibited. Please refer to Section 5.1.8 for more information. 
2.1.7 
Patients have hemoglobin (HgB) ≥ 9 g/dL, which should be done ≤ 4 
weeks prior to registration to treatment step. 
2.1.8 
Resting corrected QTc interval using the Fridericia formula (QTcF) 
should be < 450 msec/male and < 470 msec/female (as calculated 
per institutional standards) obtained from electrocardiogram (ECG), 
prior to enrollment. If resting QTc interval using the Fridericia formula 
(QTcF) is > 450 msec/male and > 470 msec/female (as calculated per 
institutional standards), then 2 additional ECGs should be performed 
2-5 minutes apart at study entry. In order to be eligible, the mean 
resting corrected QTc interval using the Fridericia formula (QTcF) 
should be < 450 msec/male and < 470 msec/female (as calculated 
per institutional standards). 
 
 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 
_____
_____ 
_____
_____
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
11 
3. AZD1775 Treatment Plan 
3.1 
Administration Schedule 
AZD1775 capsules will be administered orally, 300 mg once daily for 5 days on 2 
days off, 2 weeks on 1 week off, per cycle. Each cycle is 21 days. Patients will be 
asked to maintain a Study Medication Diary/pill calendar (Appendix I) and record 
each dose of medication. Patients will be given instructions for completing the pill 
calendar and will be asked to return it to the clinic staff at the end of each cycle. 
Cycles will be repeated until disease progression or as noted in Section 3.6. 
Radiologic assessment of disease status will be performed every 3 cycles. 
Since there is a potential for interaction of AZD1775 with other concomitantly 
administered drugs through the cytochrome P450 system, the case report form 
must capture the concurrent use of all other drugs, over-the-counter medications, 
or alternative therapies.   
3.2 
Adverse Event Reporting Requirements 
The Adverse Event Reporting Requirements for all EAY131 subprotocols are 
outlined in the MATCH MASTER protocol.  Please refer to those guidelines when 
determining if an event qualifies as a Serious Adverse Event (SAE) and requires 
expedited reporting via CTEP’s Adverse Event Reporting System (CTEP-AERS). 
In addition, the following section outlines agent specific requirements and must 
be followed to ensure all reporting requirements are met. 
3.2.1 
Additional instructions, requirements and exceptions for protocol 
EAY131 – Subprotocol Z1I 
Additional Instructions 
For instructions on how to specifically report events that result in 
persistent or significant disability/incapacity, congenital anomaly, 
or birth defect events via CTEP-AERS, please contact the AEMD 
Help Desk at aemd@tech-res.com or 301-897-7497. This will 
need to be discussed on a case-by-case basis. 
 
EAY131 – Subprotocol Z1I specific expedited reporting 
requirements: 
• 
Pregnancies:  Pregnancies and suspected pregnancies 
(including a positive or inconclusive pregnancy test, regardless 
of age or disease state) occurring while the female patient is on 
AZD1775, or within 28 days of the female patient’s last dose of 
AZD1775, are considered immediately reportable events. The 
pregnancy, suspected pregnancy, or positive/ inconclusive 
pregnancy test must be reported via CTEP-AERS within 24 
hours of the Investigator’s knowledge. Please refer to Appendix 
VIII in MATCH Master Protocol for detailed instructions on how 
to report the occurrence of a pregnancy as well as the outcome 
of all pregnancies. 
 
Rev. Add17 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
12 
EAY131 – Subprotocol Z1I specific expedited reporting 
exceptions: 
For Subprotocol Z1I, the adverse events listed below do not 
require expedited reporting via CTEP-AERS: 
• 
If an AE meets the reporting requirements of the protocol, and 
it is listed on the SPEER, it should ONLY be reported via 
CTEP-AERS if the grade being reported exceeds the grade 
listed in the parentheses next to the event. 
3.2.2 
Second Primary Cancer Reporting Requirements 
All cases of second primary cancers, including acute myeloid 
leukemia (AML) and myelodysplastic syndrome (MDS), that occur 
following treatment on NCI-sponsored trials must be reported to 
ECOG-ACRIN using Medidata Rave 
• 
A second malignancy is a cancer that is UNRELATED to any 
prior anti-cancer treatment (including the treatment on this 
protocol).  Second malignancies require ONLY routine reporting 
as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days. 
2. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave confirming the diagnosis. 
3. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave. 
• 
A secondary malignancy is a cancer CAUSED BY any prior anti-
cancer treatment (including the treatment on this protocol). 
Secondary malignancies require both routine and expedited 
reporting as follows: 
1. Complete a Second Primary Form in Medidata Rave within 14 
days 
2. Report the diagnosis via CTEP-AERS at http://ctep.cancer.gov  
Report under a.) leukemia secondary to oncology 
chemotherapy, b.) myelodysplastic syndrome, or c.) treatment 
related secondary malignancy 
3. Upload a copy of the pathology report to ECOG-ACRIN via 
Medidata Rave and submit a copy to NCI/CTEP confirming the 
diagnosis. 
4. If the patient has been diagnosed with AML/MDS, upload a 
copy of the cytogenetics report (if available) to ECOG-ACRIN 
via Medidata Rave and submit a copy to NCI/CTEP. 
NOTE: 
The Second Primary Form and the CTEP-AERS report 
should not be used to report recurrence or development of 
metastatic disease. 
NOTE: 
If a patient has been enrolled in more than one NCI-
sponsored study, the Second Primary Form must be 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
13 
submitted for the most recent trial. ECOG-ACRIN must be 
provided with a copy of the form and the associated 
pathology report and cytogenetics report (if available) even 
if ECOG-ACRIN was not the patient's most recent trial. 
NOTE: 
Once data regarding survival and remission status are no 
longer required by the protocol, no follow-up data should 
be submitted via CTEP-AERS or by the Second Primary 
Form. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
14 
3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for AZD1775 
(MK-1775, NSC 751084) 
The Comprehensive Adverse Events and Potential Risks list (CAEPR) provides a 
single list of reported and/or potential adverse events (AE) associated with an 
agent using a uniform presentation of events by body system. In addition to the 
comprehensive list, a subset, the Specific Protocol Exceptions to Expedited 
Reporting (SPEER), appears in a separate column and is identified with bold and 
italicized text. This subset of AEs (SPEER) is a list of events that are protocol 
specific exceptions to expedited reporting to NCI (except as noted below). Refer 
to the 'CTEP, NCI Guidelines: Adverse Event Reporting Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguide
lines.pdf for further clarification. Frequency is provided based on 313 patients. 
Below is the CAEPR for AZD1775 (MK-1775, NSC 751084). 
NOTE: 
If an AE meets the reporting requirements of the protocol, and it is 
listed on the SPEER, it should ONLY be reported via CTEP-AERS if 
the grade being reported exceeds the grade listed in the parentheses 
next to the event. 
Version 2.6, May 14, 20191 
 
Adverse Events with Possible 
Relationship to AZD1775 (adavosertib) 
(CTCAE 5.0 Term) 
[n= 313] 
 
 
 
Specific Protocol 
Exceptions to Expedited 
Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)  
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
 
Anemia 
 
 Anemia (Gr 3) 
 
Febrile neutropenia 
  
CARDIAC DISORDERS 
  
 
Atrial fibrillation 
  
 
Supraventricular tachycardia 
  
GASTROINTESTINAL DISORDERS 
  
Abdominal pain 
 
 Abdominal pain (Gr 2) 
Constipation 
 
 Constipation (Gr 2) 
Diarrhea 
 
 
 Diarrhea (Gr 3) 
Dyspepsia 
 
  
 
Gastrointestinal hemorrhage2   
Mucositis oral 
 
 Mucositis oral (Gr 2) 
Nausea 
 
 
 Nausea (Gr 3) 
Vomiting 
 
 
 Vomiting (Gr 3) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
Edema limbs 
 
 Edema limbs (Gr 2) 
Fatigue 
 
 
 Fatigue (Gr 3) 
Fever 
 
 Fever (Gr 2) 
HEPATOBILIARY DISORDERS 
  
 
Hepatobiliary disorders - 
Other (hepatitis) 
  
INFECTIONS AND INFESTATIONS 
  
 Infection3 
 
 Infection3 (Gr 3)  
INVESTIGATIONS 
  
Rev. Add14 
Rev. Add17 
Rev. Add21 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
15 
 
Adverse Events with Possible 
Relationship to AZD1775 (adavosertib) 
(CTCAE 5.0 Term) 
[n= 313] 
 
 
 
Specific Protocol 
Exceptions to Expedited 
Reporting (SPEER) 
 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)  
Alanine aminotransferase 
increased 
 
 Alanine aminotransferase 
increased (Gr 3) 
 
Electrocardiogram QT 
corrected interval prolonged 
  
Lymphocyte count 
decreased 
 
  
Neutrophil count 
decreased 
 
 Neutrophil count decreased 
(Gr 4)  
Platelet count decreased  
 Platelet count decreased (Gr 
4) 
White blood cell 
decreased 
 
 White blood cell decreased 
(Gr 4) 
METABOLISM AND NUTRITION DISORDERS 
  
Anorexia 
 
 Anorexia (Gr 2) 
Dehydration 
 
  
Hypokalemia 
 
 Hypokalemia (Gr 2) 
Hypomagnesemia 
 
 Hypomagnesemia (Gr 2) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
  
Back pain 
 
 Back pain (Gr 2) 
Myalgia 
 
 Myalgia (Gr 2) 
NERVOUS SYSTEM DISORDERS 
  
Dizziness 
 
 Dizziness (Gr 2) 
Headache 
 
 Headache (Gr 2) 
 
Intracranial hemorrhage 
  
PSYCHIATRIC DISORDERS 
  
Insomnia 
 
  
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
Cough 
 
 Cough (Gr 2) 
Dyspnea 
 
 Dyspnea (Gr 2) 
 
Hypoxia 
  
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
Rash4 
 
 Rash4 (Gr 2) 
VASCULAR DISORDERS 
  
 
Phlebitis 
  
1 This table will be updated as the toxicity profile of the agent is revised.  Updates will be distributed to all 
Principal Investigators at the time of revision.  The current version can be obtained by contacting 
PIO@CTEP.NCI.NIH.GOV.  Your name, the name of the investigator, the protocol and the agent should 
be included in the e-mail. 
2 Gastrointestinal hemorrhage includes Anal hemorrhage, Cecal hemorrhage, Colonic hemorrhage, 
Duodenal hemorrhage, Esophageal hemorrhage, Esophageal varices hemorrhage, Gastric hemorrhage, 
Hemorrhoidal hemorrhage, Ileal hemorrhage, Intra-abdominal hemorrhage, Jejunal hemorrhage, Lower 
gastrointestinal hemorrhage, Oral hemorrhage, Pancreatic hemorrhage, Rectal hemorrhage, 
Retroperitoneal hemorrhage, and Upper gastrointestinal hemorrhage under the GASTROINTESTINAL 
DISORDERS SOC. 
3 Infection includes all 75 sites of infection under the INFECTIONS AND INFESTATIONS SOC. 
4 Rash may include rash, erythema, eczema, and rash maculo-papular. 
5 Peripheral neuropathy includes both peripheral motor neuropathy and peripheral sensory neuropathy. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
16 
6 Acute kidney injury includes renal impairment and acute renal insufficiency. 
Adverse events reported on AZD1775 (adavosertib) trials, but for which there is 
insufficient evidence to suggest that there was a reasonable possibility that AZD1775 
(adavosertib) caused the adverse event: 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and lymphatic system disorders - 
Other (pancytopenia); Blood and lymphatic system disorders - Other (thrombocytosis); 
Leukocytosis 
CARDIAC DISORDERS - Cardiac disorders - Other (cardiomegaly); Chest pain - cardiac; 
Myocardial infarction; Palpitations; Sinus bradycardia; Sinus tachycardia 
EAR AND LABYRINTH DISORDERS - Ear pain; Hearing impaired; Tinnitus 
EYE DISORDERS - Blurred vision; Cataract; Eye disorders - Other (eye swelling); Eye pain; 
Keratitis; Photophobia; Scleral disorder; Vision decreased; Watering eyes 
GASTROINTESTINAL DISORDERS - Abdominal distension; Anal pain; Ascites; Belching; 
Bloating; Cheilitis; Colitis; Colonic obstruction; Dry mouth; Duodenal ulcer; Dysphagia; 
Enterocolitis; Flatulence; Gastric ulcer; Gastritis; Hemorrhoids; Oral pain; Rectal pain; Small 
intestinal obstruction 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Death NOS; 
Edema trunk; Flu like symptoms; Gait disturbance; General disorders and administration site 
conditions - Other (catheter site pain); Infusion site extravasation; Malaise; Non-cardiac chest 
pain; Pain 
IMMUNE SYSTEM DISORDERS - Allergic reaction; Anaphylaxis; Cytokine release syndrome 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Fall; Injury, poisoning and 
procedural complications - Other (excoriation); Injury, poisoning and procedural complications - 
Other (ligament sprain) 
INVESTIGATIONS - Alkaline phosphatase increased; Aspartate aminotransferase increased; 
Blood bilirubin increased; Creatinine increased; GGT increased; Investigations - Other (blood 
urea increased); Lymphocyte count increased; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Alkalosis; Hypercalcemia; Hyperglycemia; 
Hyperkalemia; Hyperuricemia; Hypoalbuminemia; Hypocalcemia; Hyponatremia; 
Hypophosphatemia; Tumor lysis syndrome 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthralgia; Arthritis; Bone 
pain; Flank pain; Generalized muscle weakness; Muscle cramp; Muscle weakness lower limb; 
Musculoskeletal and connective tissue disorder - Other (groin pain); Neck pain; Pain in 
extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) - 
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other (carcinoid tumor); 
Tumor pain 
NERVOUS SYSTEM DISORDERS - Central nervous system necrosis; Cognitive disturbance; 
Dysesthesia; Dysgeusia; Encephalopathy; Lethargy; Nervous system disorders - Other 
(hemiparesis); Paresthesia; Peripheral neuropathy5; Presyncope; Somnolence; Syncope 
PSYCHIATRIC DISORDERS - Agitation; Anxiety; Confusion; Depression 
RENAL AND URINARY DISORDERS - Acute kidney injury6; Hematuria; Urinary frequency; 
Urinary incontinence; Urinary retention; Urinary tract pain 
REPRODUCTIVE SYSTEM AND BREAST DISORDERS - Genital edema; Reproductive 
system and breast disorders - Other (female genital tract fistula) 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
17 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Allergic rhinitis; 
Bronchopulmonary hemorrhage; Epistaxis; Hiccups; Nasal congestion; Pleural effusion; 
Pneumonitis; Pulmonary hypertension; Respiratory, thoracic and mediastinal disorders - Other 
(diaphragmalgia); Voice alteration; Wheezing 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Alopecia; Bullous dermatitis; Dry skin; 
Hyperhidrosis; Pain of skin; Palmar-plantar erythrodysesthesia syndrome; Pruritus; Purpura; 
Rash acneiform; Skin ulceration; Urticaria 
VASCULAR DISORDERS - Flushing; Hematoma; Hot flashes; Hypertension; Hypotension; 
Thromboembolic event 
NOTE: 
AZD1775 (adavosertib) in combination with other agents could cause an 
exacerbation of any adverse event currently known to be caused by the other agent, 
or the combination may result in events never previously associated with either 
agent. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
18 
3.4 
Dose Modifications  
All toxicity grades below are described using the NCI Common Terminology 
Criteria for Adverse Events (CTCAE) version 4.0. 
All appropriate treatment areas should have access to a copy of the CTCAE 
version 4.0. A copy of the CTCAE version 4.0 can be downloaded from the 
CTEP website (http://ctep.cancer.gov). 
Toxicities should have resolved to ≤Grade 2 prior to starting the next cycle.  
Treatment may be delayed for a maximum of 2 weeks beyond the actual cycle 
length of 21 days for toxicities that develop and do not resolve as defined above.  
Beyond two weeks, the patient will not receive further therapy on this protocol 
and will be followed for resolution of toxicities.   
Treatments may be delayed up to 7 days past the end of the previous cycle of 21 
days for scheduling conflicts at the discretion of the investigator.  
Patients will be allowed up to 2 dose reductions.  If more than 2 dose reductions 
are required, the patient will be removed from the study. 
3.4.1 
Dose Reduction:  
Dose Level 
Unit dose 
-1 
200 mg 
-2 
175 mg 
Dosing regimen will remain as AZD1775 capsules administered orally 
for a total of 10 doses, 300 mg PO daily for 5 days on and 2 days off, 
2 weeks on and 1 week off, every 21 day cycle. 
Dose modifications are defined below: No dose interruptions or 
modifications will be made for any grade alopecia or lymphopenia.  
3.4.2 
Grade 2 Drug-related toxicity: No changes will be made to the dose 
of AZD1775 for Grade 2 toxicities.  Therapy will not be interrupted for 
Grade 2 hematologic toxicities. 
3.4.3 
Grade 3-4 Drug-related non-hematologic toxicities: Doses of 
AZD1775 will be held until toxicities recover to ≤ Grade 2 prior to re-
initiating treatment at the next lower dose level. Electrolyte 
abnormalities will not require dose reduction if resolution to Grade 2 or 
less is documented within 72 hours. Dose modifications for nausea, 
vomiting, and diarrhea will be made only if they are refractory to 
treatment (See Section 3.5).  
3.4.4 
Grade 3 Drug-related hematologic toxicities: Dose of AZD1775 will 
be held until hematologic toxicities, except lymphopenia, or 
leukopenia in the absence of neutropenia, have resolved to ≤ Grade 2 
prior to re-initiating treatment at the same dose level. 
3.4.5 
Grade 4 Drug-related Hematologic Toxicities: Dose of AZD1775 
will be held until hematologic toxicities, except lymphopenia, or 
leukopenia in the absence of neutropenia, have resolved to ≤ Grade 2 
prior to re-initiating treatment at the next lower dose level. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
19 
3.5 
Supportive Care  
3.5.1 
All supportive measures consistent with optimal patient care will be 
given throughout the study. 
3.5.2 
Nausea/Vomiting 
All patients must receive a 5-HT3 antagonist, ondansetron (Zofran) 8 
mg PO QD or granisetron (Kytril) 1 mg PO QD prior to each dose of 
AZD1775. If nausea and vomiting continue, a second dose of 
antiemetics can be taken 8 hours later if necessary. In addition, 
dexamethasone 4 mg PO may be given prior to each AZD1775 dose 
in cases of continued nausea/vomiting unless contraindicated or not 
well-tolerated. Dexamethasone or the 5-HT3 antagonist may be given 
by IV as needed. 
Promethazine (Phenergan), prochlorperazine (Compazine), and 
benzodiazepine may still be used as additional adjunctive treatments 
during AZD1775 therapy. 
Please note: aprepitant [Emend] and fosaprepitant are not permitted 
due to known DDIs. 
Patients should be strongly encouraged to maintain liberal oral fluid 
intake. 
Suitable alternative medications may be used, with adequate 
justification, in those studies where the use of any of the above 
medications might interfere with other study procedures or are 
deemed insufficient. 
3.5.3 
Diarrhea 
If diarrhea develops and does not have an identifiable cause other 
than study drug administration, anti-diarrheals such as Lomotil 
(diphenoxylate HCl 2.5 mg + atropine sulfate 0.025 mg/tablet) dosed 
according to package insert or loperamide 4 mg po after the first 
unformed stool with 2 mg po with every 2 hours (4 mg every 4 hours 
while asleep), until resolution of episode for at least 12 hours (no 
more than 16 mg of loperamide during a 24-hour period). This 
regimen can be repeated for each diarrheal episode. Diarrhea will be 
considered refractory if it does not resolve within 24 hours ≤ to Grade 
2 with the above regimen (maximum of 16 mg of loperamide in a 24-
hour period). If the patient develops blood or mucus in the stool, 
dehydration, or hemodynamic instability, or fever along with the 
diarrhea, anti-diarrheals will be discontinued and the patient will be 
treated with IV fluids and antibiotics as medically indicated. 
3.5.4 
Neutropenia 
Febrile neutropenia is a life-threatening complication requiring 
hospitalization and urgent broad spectrum antibiotics, as well as an 
aggressive search for the source and microbial cause of the episode.  
Growth factors to prevent neutropenia will not be administered 
prophylactically. If necessary, they may be administered according to 
accepted American Society of Clinical Oncology (ASCO) guidelines to 
allow re-treatment. 
Rev. Add13 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
20 
3.5.5 
Anemia 
Symptomatic anemia should be treated with red blood cell transfusion 
and is recommended if the hemoglobin falls below 8 g/dL. The 
initiation of erythropoietic therapy for the management of 
chemotherapy-induced anemia follows the American Society of 
Hematology/ASCO clinical practice guidelines (http://www.asco.org). 
3.5.6 
Thrombocytopenia 
Thrombocytopenia will be treated conservatively. In the absence of 
bleeding, or a necessary invasive procedure, platelet transfusions 
should be given for a platelet count ≤ 10,000/mm3. If invasive 
procedure(s) is (are) planned, or the patient develops bleeding, 
platelet transfusions should be administered in accordance with the 
standard of practice, usually maintaining a platelet count above 
50,000/mm3. 
3.6 
Duration of Agent-Specific Treatment  
In the absence of treatment delays due to adverse event(s), treatment may 
continue until one of the following criteria applies: 
• 
Extraordinary Medical Circumstances: If at any time the constraints of this 
protocol are detrimental to the patient's health, protocol treatment should be 
discontinued. In this event submit forms according to the instructions in the 
MATCH Forms Packet 
• 
Patient withdraws consent 
• 
Patient experiences unacceptable toxicity 
• 
Non-protocol therapies are administered 
• 
Disease progression 
3.7 
Duration of Follow-Up  
Refer to the MATCH Master Protocol for specifics on the duration of follow-up. 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
21 
4. Study Parameters 
4.1 
Therapeutic Parameters for AZD1775 Treatment  
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving AZD1775 treatment. 
NOTE: 
All assessments required prior to registration to treatment should be done ≤ 4 weeks prior to registration to 
Steps 1, 3, 5, 7, excluding the radiologic evaluation and electrocardiogram (ECG). 
Test/Assessment 
Prior to Registration to 
Treatment 
Treatment 
End of 
Treatment 
Follow UpF 
Every Cycle, prior 
to treatment 
Every 3 
Cycles 
H&P, Weight, Vital signsA 
X 
 XI 
 
 
X 
Performance status 
X 
 XI 
 
 
X 
CBC w/diff, pltsB 
X 
 XI 
 
 
X 
Serum chemistryB 
X 
 XI 
 
 
X 
Hemoglobin 
X 
 
 
 
 
Radiologic evaluationD 
X 
 
 XD 
 
 XF 
-HCGC 
X 
X 
 
 
 
Toxicity AssessmentG 
 
X 
 
X 
 XF 
Pill Count/DiaryH 
 
X 
 
X 
 
ECGJ 
X 
 X 
 
 
 
Tumor biopsy and blood sample for MATCH Master ProtocolE 
 
 
X 
 X 
 
A. History and physical, including vital signs and weight at the start of each cycle (up to 3 days before start of new cycle). 
B. Albumin, alkaline phosphatase, total bilirubin, bicarbonate, BUN, calcium, creatinine, glucose, phosphorus, potassium,  SGOT[AST], 
SGPT[ALT], sodium, magnesium, and serum tumor markers (including LDH, PSA if appropriate). For eligibility purposes, participants with 
creatinine levels above institutional normal, Cockcroft-Gault will be used to calculate creatinine clearance. CBC w/diff, platelets and serum 
chemistries should be performed on cycle 1, day 1 (or up to 7 days prior), and at the start of each subsequent cycle (up to 3 days before start of 
new cycle). CBC with differential will be performed more frequently in patients with grade 4 neutropenia or thrombocytopenia until resolution to  
≤ grade 3. CBC and serum chemistries are only required in follow-up until values return to pre-treatment levels or until progressive disease. 
C. Blood pregnancy test (women of childbearing potential) required prior to beginning treatment and prior to the start of each cycle. 
D. Disease measurements are repeated every 3 cycles until PD or start of another MATCH treatment step. The baseline evaluation should be 
performed as closely as possible to the beginning of treatment and never more than 6 weeks before registration to treatment step. For multiple 
Rev. Add13 
Rev. Add13 
Rev. Add13 
Rev. Add13 
Rev. Add13 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
22 
myeloma patients, please refer to Section 6.4 of the MATCH Master Protocol for additional information on myeloma response criteria and the 
required disease assessments. Documentation (radiologic) must be provided for patients removed from study for progressive disease. 
E. Additional blood specimens and/or biopsies are to be submitted from consenting patients per Section 9.3.2 of the MATCH Master Protocol. 
Submit at the following time points, as applicable: 
• 
Blood specimens are to be submitted at the end of Cycle 2 (prior to start of Cycle 3 treatment). If patient progresses or treatment is 
discontinued prior to Cycle 3, collect the blood at that time instead. On-treatment kits for blood sample collections will be automatically 
shipped to sites upon registration to the treatment step. 
• 
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4). 
• 
At end of all MATCH study treatments, blood specimens and/or research biopsy after consent and registration to Step 8 
Please refer to Section 4 of the MATCH Master Protocol to determine whether the patient proceeds to the next screening step or to follow-up 
(with a potential end of treatment biopsy for research purposes on Step 8). Samples are to be submitted as outlined in Section 9 of the MATCH 
Master Protocol. To order Step 2/4 Screening or Step 8 kits, complete the EAY131 Collection and Shipping Kit Order Form (See Appendix XII of 
the MATCH Master Protocol) and fax to 713-563-6506. 
F. Every 3 months if patient is < 2 years from study entry, and every 6 months for year 3. Toxicity assessments and radiologic evaluations are not 
required to be done during Follow Up if progression has been previously reported; however if an adverse event occurs post treatment that meets 
the SAE reporting requirements, it still must be reported via CTEP-AERS, even if progression has occurred. 
G. Site personnel should evaluate for toxicity and discuss treatment compliance with the patient in order to ensure the medication is taken correctly; 
this evaluation may be conducted by telephone or in person. The Toxicity Assessment is not required prior to Cycle 1, but is required every 
subsequent cycle. 
H. The pill calendar will be collected at the end of every cycle. The Pill Count/Diary is not required prior to Cycle 1, but is required every subsequent 
cycle. 
I. 
For Cycle 1, if the following tests/assessments occurred within 7 days of Day 1, they do not need to be repeated at this timepoint: H&P, Weight, 
Vital Signs; Performance Status; CBC w/diff, plts; Serum chemistry; Concomitant Medications. 
J. Within 8 weeks of treatment assignment. 
 
Rev. Add13 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
23 
5. Drug Formulation and Procurement 
This information has been prepared by the ECOG-ACRIN Pharmacy and Nursing 
Committees. 
Availability 
NO STARTER SUPPLIES MAY BE ORDERED. Subjects must be enrolled and assigned 
to the treatment subprotocol prior to submitting the clinical drug request to PMB. 
Drug Ordering: NCI supplied agents may be requested by eligible participating 
Investigators (or their authorized designee) at each participating institution.  
Pharmaceutical Management Branch (PMB) policy requires that drug be shipped directly 
to the institution where the patient is to be treated. PMB does not permit the transfer of 
agents between institutions (unless prior approval from PMB is obtained – see general 
information) The CTEP-assigned protocol number must be used for ordering all CTEP-
supplied investigational agents. The eligible participating investigators at each 
participating institution must be registered with CTEP, DCTD through an annual 
submission of FDA Form 1572 (Statement of Investigator), NCI Biosketch, Agent 
Shipment Form, and Financial Disclosure Form (FDF).  If there are several participating 
investigators at one institution, CTEP-supplied investigational agents for the study 
should be ordered under the name of one lead investigator at that institution. 
Submit agent requests through the PMB Online Agent Order Processing (OAOP) 
application (https://ctepcore.nci.nih.gov/OAOP) Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account 
(https://ctepcore.nci.nih.gov/iam/) and the maintenance of an “active” account status, a 
“current” password, and an active person registration status. 
NCI Supplied Agent(s) – General Information 
Questions about drug orders, transfers, returns, or accountability should be 
addressed to the PMB by calling 240-276-6575 Monday through Friday between 
8:30 AM and 4:30 PM Eastern Time or email PMBAfterHours@mail.nih.gov 
anytime. 
Drug Returns: All undispensed drug supplies should be returned to the PMB. When it is 
necessary to return study drug (e.g., sealed bottles remaining when PMB sends a stock 
recovery letter), investigators should return the study drug to the PMB using the NCI 
Return Agent Form available on the NCI home page (http://ctep.cancer.gov). 
Drug Accountability: The investigator, or a responsible party designated by the 
investigator, must maintain a careful record of the receipt, disposition, and return of 
agent received from the PMB using the NCI Investigational Agent Accountability Record 
Form for Oral Agents available on the NCI home page (http://ctep.cancer.gov). Maintain 
separate NCI Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator. 
Investigator Brochure Availability: The current versions of the IBs for PMB-supplied 
agents will be accessible to site investigators and research staff through the PMB Online 
Agent Order Processing (OAOP) application.  Access to OAOP requires the 
establishment of a CTEP Identity and Access Management (IAM) account and the 
maintenance of an “active” account status, a “current” password, and active person 
registration status.  Questions about IB access may be directed to the PMB IB 
coordinator at IBCoordinator@mail.nih.gov. 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
24 
5.1 
AZD1775 (NSC 751084) 
5.1.1 
Other Names  
MK-1775 
5.1.2 
Classification  
Inhibitor of WEE1 kinase 
5.1.3 
Mode of Action  
AZD1775 inhibits WEE1 which phosphorylates and inhibits cyclin-
dependent kinases 1 (CDK1) and 2 (CDK2), and is involved in 
regulation of the intra-S and G2 cell cycle checkpoints.  In in vitro and 
in vivo preclinical models, AZD1775 selectively enhanced 
chemotherapy induced death of cells deficient in p53 signaling. 
5.1.4 
Storage and Stability  
Storage: Store at 2 to 30˚C (36 to 86˚F). Do not freeze.  
Stability: Shelf-life stability studies of AZD1775 capsules are ongoing. 
5.1.5 
Dose Specifics  
AZD1775 capsules will be administered orally for a total of 10 doses, 
300 mg once daily for 5 days on and 2 days off, 2 weeks on and 1 
week off, every 21 day schedule 
5.1.6 
Preparation 
AZD1775 is supplied by AstraZeneca and distributed by the 
Pharmaceutical Management Branch, CTEP/DCTD/NCI as capsules 
available in 25 mg (yellow color, size 2 gelatin capsule) and 100 mg 
(orange color, size 2 gelatin capsule) strengths.  The dry-filled 
capsules consist of a roller-compacted granule of drug substance, 
lactose monohydrate, microcrystalline cellulose, croscarmellose 
sodium, and magnesium stearate. Each high density polypropylene 
(HDPE) bottle contains 20 capsules. 
5.1.7 
Route of Administration  
Oral administration. Take AZD1775 two hours before a meal or two 
hours after a meal. Capsules should not be opened. 
5.1.8 
Incompatibilities  
AZD1775 is primarily metabolized by CYP3A4 and is a weak, time-
dependent inhibitor of CYP3A4. Avoid concomitant CYP3A4 moderate 
or strong inhibitors/inducers, and sensitive substrates with a narrow 
therapeutic index.  AZD1775 is also a weak inhibitor of CYP2C19.  
Caution should be exercised with concomitant administration of 
sensitive substrates or substrates with a narrow therapeutic index. 
In vitro transporter studies have shown that AZD1775 was an inhibitor 
of OATP1B1, OATP1B3, MATE1, MATE2K, P-glycoprotein (P-gp) and 
breast cancer resistance protein (BCRP), and a substrate for P-gp 
and BCRP.  The PK parameters of AZD1775 could be altered if 
AZD1775 is coadministered with P-gp and BCRP inhibitors/inducers, 
and there is potential for drug-drug interactions when coadministered 
Rev. Add17 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
25 
with OATP1B1, OATP1B3, MATE1, MATE2K, P-gp and BCRP 
substrates.  This finding is particularly relevant for drugs administered 
orally where exposure is normally limited by BCRP-mediated efflux, in 
particular some statins.  Modelling has predicted a substantial 
increase in the exposure of atorvastatin when coadministered with 
AZD1775 and the use of atorvastatin is therefore prohibited. 
5.1.9 
Side Effects  
See Section 3.3 for side effects. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
26 
6. Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
Specifically, for patients enrolled in this subprotocol:  
We will plan to use banked blood on all eligible patients enrolled to perform correlative 
germline DNA genetic studies. We plan to perform germline panel sequencing on these 
samples for the proposed genes of interest and correlate these findings with clinical 
outcomes to determine whether the origin of the driver mutation (germline vs. somatic) 
alters response rates. Furthermore, we will request tumor samples from the eligibility 
biopsies to perform additional somatic genomic profiling, including confirming loss-of-
heterozygosity for the target DNA repair gene, and an assessment of overall genomic 
instability. Finally, when available, we will analyze re-biopsy samples from patients 
responding and then relapsed for mechanisms of drug resistance. These include 
reversion mutations of the target genes (e.g. BRCA1, 2), mutations in the target enzyme 
Wee1 kinase, or additional secondary genomic alterations. 
The analyses will be performed for research purposes only, on clinically annotated but 
de-identified samples. None of these results will be reported to the patients or their 
families.  
7. References 
1. Santo L, Siu KT, Raje N. Targeting Cyclin-Dependent Kinases and Cell Cycle 
Progression in Human Cancers. Semin Oncol. 2015 Dec;42(6):788-800 
2. Do K, Wilsker D, Ji J, et al. Phase I Study of Single-Agent AZD1775 (MK-1775), a 
Wee1 Kinase Inhibitor, in Patients with Refractory Solid Tumors. J Clin Oncol. 2015 
Oct 20;33(30):3409-15 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
27 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1I: AZD1775, BRCA Mutations 
Appendix I 
 
Patient Pill Calendar 
 
Pill Calendar Directions 
1. Take your scheduled dose of each capsule. 
2. If you forget, the missed capsules will not be taken later. 
3. Please bring the empty bottle or any leftover capsules and your pill calendar to your 
next clinic visit. 
4. You will take AZD1775 by mouth once a day on days 1-5 and 8-12 for a total of ten 
doses every 21 days. The drug is given in cycles; each cycle is 21 days long. 
5. Take AZD1775 on an empty stomach, two hours before a meal or two hours after a 
meal. 
6. Capsules should be swallowed whole. 
7. Store AZD1775 at room temperature. 
 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
28 
Patient Pill Calendar 
This is a calendar on which you are to record the time and number of capsules you take 
each day. You should take your scheduled dose of each capsule. Note the times and 
the number of capsules that you take each day. If you develop any side effects, 
please record them and anything you would like to tell the doctor in the space provided. 
Bring any unused capsules and your completed pill calendar to your doctor’s visits. 
AZD1775 
DAY  
Date 
Time pills 
taken 
Number 
of pills 
taken 
Use the space below to make notes about 
things you would like to tell the doctor 
(including unusual symptoms you experience, 
other medicine you have taken and anything 
else you think would be of interest.) 
Month 
Day 
Year 
 
 
1 
 
 
 
 
 
 
2 
 
 
 
 
 
 
3 
 
 
 
 
 
 
4 
 
 
 
 
 
 
5 
 
 
 
 
 
 
6 
 
 
 
 
 
 
7 
 
 
 
 
 
 
8 
 
 
 
 
 
 
9 
 
 
 
 
 
 
10 
 
 
 
 
 
 
11 
 
 
 
 
 
 
12 
 
 
 
 
 
 
13 
 
 
 
 
 
 
14 
 
 
 
 
 
 
15 
 
 
 
 
 
 
16 
 
 
 
 
 
 
17 
 
 
 
 
 
 
18 
 
 
 
 
 
 
19 
 
 
 
 
 
 
20 
 
 
 
 
 
 
21 
 
 
 
 
 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
29 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1I: AZD1775, BRCA Mutations 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
30 
Appendix II 
 
Actionable Mutations for Sub-Protocol EAY131-Z1I 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
31 
Gene Name 
Variant ID 
Variant Type 
Variant Description 
Level of Evidence 
Code 
BRCA2 
CV51385 
SNV 
p.Met1Arg 
3 
BRCA2 
CV37871 
SNV 
p.Met1Ile 
3 
BRCA2 
CV51711 
SNV 
p.Val159Met 
3 
BRCA2 
CV51708 
SNV 
splicesite 
3 
BRCA2 
CV37923 
SNV 
splicesite 
3 
BRCA2 
CV52058 
SNV 
p.Val211Ile 
3 
BRCA2 
CV38035 
SNV 
p.Val211Leu 
3 
BRCA2 
CV236264 
SNV 
splicesite 
3 
BRCA2 
CV52242 
SNV 
p.Arg2336Leu 
3 
BRCA2 
CV52241 
SNV 
p.Arg2336Pro 
3 
BRCA2 
CV52246 
SNV 
splicesite 
3 
BRCA2 
CV52362 
SNV 
splicesite 
3 
BRCA2 
CV38110 
SNV 
splicesite 
3 
BRCA2 
CV38125 
SNV 
p.Trp2626Cys 
3 
BRCA2 
CV52430 
SNV 
p.Ile2627Phe 
3 
BRCA2 
CV52455 
SNV 
p.Arg2659Thr 
3 
BRCA2 
CV52462 
SNV 
p.Glu2663Val 
3 
BRCA2 
CV52471 
SNV 
p.Ser2670Leu 
3 
BRCA2 
CV9340 
SNV 
p.Thr2722Arg 
3 
BRCA2 
CV52515 
SNV 
p.Asp2723His 
3 
BRCA2 
CV38141 
SNV 
p.Asp2723Gly 
3 
BRCA2 
CV52535 
SNV 
p.Gly2748Asp 
3 
BRCA2 
CV52602 
SNV 
splicesite 
3 
BRCA2 
CV38198 
SNV 
splicesite 
3 
BRCA2 
CV52712 
SNV 
splicesite 
3 
BRCA2 
COSM185479 
SNV 
p.Arg3052Trp 
3 
BRCA1 
CV55611 
SNV 
p.Val1838Glu 
3 
BRCA1 
CV125857 
SNV 
splicesite 
3 
BRCA1 
CV55588 
SNV 
p.Ala1823Thr 
3 
BRCA1 
COSM436662 
SNV 
p.Gly1788Val 
3 
BRCA1 
CV55548 
SNV 
p.Cys1787Ser 
3 
BRCA1 
CV236263 
Complex 
splicesite 
3 
BRCA1 
CV55527 
SNV 
splicesite 
3 
BRCA1 
CV17695 
SNV 
p.Met1775Lys 
3 
BRCA1 
CV17694 
SNV 
p.Met1775Arg 
3 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
32 
BRCA1 
CV37656 
SNV 
p.Ile1766Ser 
3 
BRCA1 
CV55510 
SNV 
p.Leu1764Pro 
3 
BRCA1 
CV236262 
Indel 
splicesite 
3 
BRCA1 
COSM35895 
SNV 
splicesite 
3 
BRCA1 
CV55461 
SNV 
p.Gly1738Arg 
3 
BRCA1 
CV55451 
SNV 
splicesite 
3 
BRCA1 
CV37643 
SNV 
splicesite 
3 
BRCA1 
CV55425 
SNV 
splicesite 
3 
BRCA1 
CV55423 
SNV 
splicesite 
3 
BRCA1 
CV55414 
SNV 
p.Ser1715Arg 
3 
BRCA1 
CV55407 
SNV 
p.Ala1708Glu 
3 
BRCA1 
CV37638 
SNV 
p.Gly1706Glu 
3 
BRCA1 
CV55396 
SNV 
p.Arg1699Trp 
3 
BRCA1 
CV37629 
SNV 
splicesite 
3 
BRCA1 
CV37633 
SNV 
p.Asp1692His 
3 
BRCA1 
CV37632 
SNV 
p.Asp1692Asn 
3 
BRCA1 
CV55376 
SNV 
p.Asp1692Tyr 
3 
BRCA1 
CV55365 
SNV 
p.Thr1685Ile 
3 
BRCA1 
CV55364 
SNV 
p.Thr1685Ala 
3 
BRCA1 
CV182165 
SNV 
splicesite 
3 
BRCA1 
CV55344 
SNV 
splicesite 
3 
BRCA1 
CV37620 
SNV 
splicesite 
3 
BRCA1 
CV246100 
SNV 
splicesite 
3 
BRCA1 
CV55342 
SNV 
splicesite 
3 
BRCA1 
CV37619 
SNV 
splicesite 
3 
BRCA1 
CV125722 
SNV 
splicesite 
3 
BRCA1 
CV55256 
SNV 
splicesite 
3 
BRCA1 
CV37604 
SNV 
p.Glu1559Lys 
3 
BRCA1 
CV37605 
SNV 
p.Glu1559Gln 
3 
BRCA1 
CV37598 
SNV 
p.Arg1495Met 
3 
BRCA1 
CV37584 
SNV 
splicesite 
3 
BRCA1 
CV55131 
SNV 
p.Gln1395= 
3 
BRCA1 
CV37567 
SNV 
splicesite 
3 
BRCA1 
CV37674 
SNV 
splicesite 
3 
BRCA1 
COSM1559465 
SNV 
splicesite 
3 
BRCA1 
CV54751 
SNV 
splicesite 
3 
BRCA1 
CV37501 
SNV 
splicesite 
3 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
33 
BRCA1 
CV125616 
SNV 
splicesite 
3 
BRCA1 
CV37449 
SNV 
splicesite 
3 
BRCA1 
CV37450 
SNV 
splicesite 
3 
BRCA1 
CV54467 
SNV 
splicesite 
3 
BRCA1 
CV54471 
SNV 
p.Arg71Lys 
3 
BRCA1 
CV17693 
SNV 
p.Arg71Gly 
3 
BRCA1 
CV54400 
SNV 
p.Cys64Tyr 
3 
BRCA1 
CV17661 
SNV 
p.Cys61Gly 
3 
BRCA1 
CV54199 
SNV 
p.Cys44Tyr 
3 
BRCA1 
CV54191 
SNV 
p.Cys44Ser 
3 
BRCA1 
CV54166 
SNV 
p.His41Arg 
3 
BRCA1 
CV54152 
SNV 
p.Cys39Arg 
3 
BRCA1 
CV54131 
SNV 
p.Thr37Lys 
3 
BRCA1 
CV55656 
SNV 
p.Leu22Ser 
3 
BRCA1 
CV55072 
SNV 
p.Met1Ile 
3 
BRCA1 
CV54746 
SNV 
p.Met1Arg 
3 
BRCA1 
CV54745 
SNV 
p.Met1Thr 
3 
BRCA1 
CV54432 
SNV 
p.Met1Val 
3 
A function has been implemented in MATCHBOX to identify any deleterious mutations in BRCA 
with a Level of Evidence of code 3 or higher not listed in the table above. Please refer to Section 
1.4.2 of the MATCH Master Protocol for more information. 
 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
34 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1I: AZD1775, BRCA Mutations 
Appendix III 
 
Patient Drug Information Handout and Wallet Card 
Information for Patients, Their Caregivers and Non-Study Healthcare Team on Possible 
Interactions with Other Drugs and Herbal Supplements 
The patient ____________________________ is enrolled on a clinical trial using the 
experimental study drug, AZD1775. This clinical trial is sponsored by the National Cancer 
Institute. This form is addressed to the patient, but includes important information for others who 
care for this patient. 
These are the things that you as a healthcare provider need to know: 
AZD1775 interacts with certain specific enzymes in the liver and certain transport proteins that 
help move drugs in and out of cells. 
• 
The enzymes in question are CYP 3A4 and 2C19. AZD1775 is broken down by CYP 3A4 
and may be affected by other drugs that inhibit or induce these enzymes. AZD1775 is an 
inhibitor of CYP 3A4 and 2C19 and may affect the metabolism of other drugs. 
• 
The proteins in question are OATP1B1, OATP1B3, MATE1, MATE2K, P-gp, and BCRP. 
AZD1775 is a substrate of P-gp and BCRP and may be affected by other drugs that inhibit 
or induce these transporters. AZD1775 is an inhibitor of OATP1B1, OATP1B3, MATE1, 
MATE2K, P-gp, and BCRP and may affect transport of other drugs in and out of cells.  
To the patient: Take this paper with you to your medical appointments and keep the 
attached information card in your wallet. 
AZD1775 may interact with other drugs which can cause side effects. For this reason, it is very 
important to tell your study doctors of any medicines you are taking before you enroll onto this 
clinical trial.  It is also very important to tell your doctors if you stop taking any regular 
medicines, or if you start taking a new medicine while you take part in this study.  When you talk 
about your current medications with your doctors, include medicine you buy without a 
prescription (over-the-counter remedy), or any herbal supplements such as St. John’s Wort.  It 
is helpful to bring your medication bottles or an updated medication list with you. 
Many health care providers can write prescriptions. You must tell all of your health care 
providers (doctors, physician assistants, nurse practitioners, pharmacists) you are taking part in 
a clinical trial. 
These are the things that you and they need to know: 
AZD1775 must be used very carefully with other medicines that use certain liver enzymes or 
transport proteins to be effective or to be cleared from your system. Before you enroll onto 
the clinical trial, your study doctor will work with your regular health care providers to review any 
medicines and herbal supplements that are considered “strong inducers/inhibitors or substrates 
of CYP 3A4, 2C19, OATP1B1, OATP1B3, MATE1, MATE2K, P-gp, and BCRP.” 
• 
Please be very careful!  Over-the-counter drugs (including herbal supplements) may contain 
ingredients that could interact with your study drug.  Speak to your doctors or pharmacist to 
determine if there could be any side effects.  

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
35 
• 
Your regular health care provider should check a frequently updated medical reference or 
call your study doctor before prescribing any new medicine or discontinuing any medicine. 
Your study doctor’s name is 
_____________________________________ 
and he or she can be contacted at: 
_____________________________________. 
 
 
 
 
AZD1775 interacts with CYP 3A4, 2C19, OATP1B1, 
OATP1B3, MATE1, MATE2K, P-gp, and BCRP, and 
must be used very carefully with other medicines that 
interact with these enzymes and proteins. 
➢ Before you enroll onto the clinical trial, your study 
doctor will work with your regular health care providers 
to review any medicines and herbal supplements that 
are considered “strong inducers/inhibitors or 
substrates of CYP 3A4, 2C19, OATP1B1, OATP1B3, 
MATE1, MATE2K, P-gp, and BCRP” 
➢ Before prescribing new medicines, your regular 
prescribers should go to a frequently-updated medical 
reference for a list of drugs to avoid, or contact your 
study doctor.   
➢ Your study doctor’s name is  
 
________________________ 
and can be contacted at  
 
_________________________.  
STUDY DRUG INFORMATION WALLET CARD   
 
You are enrolled on a clinical trial using the experimental 
study drug AZD1775. This clinical trial is sponsored by 
the NCI.  AZD1775 may interact with drugs that are 
processed by your liver, or use certain transport 
proteins in your body.  Because of this, it is very 
important to: 
➢ Tell your doctors if you stop taking any medicines or if 
you start taking any new medicines. 
➢ Tell all of your health care providers (doctors, physician 
assistants, nurse practitioners, or pharmacists) that you 
are taking part in a clinical trial. 
➢ Check with your doctor or pharmacist whenever you 
need to use an over-the-counter medicine or herbal 
supplement. 

ECOG-ACRIN 
EAY131-Z1I 
Cancer Research Group 
Version Date: July 10, 2019 
36 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1I: AZD1775, BRCA Mutations 
Appendix IV 
 
Patient Handout for Management of Diarrhea 
If you develop diarrhea, call your study team. If you do not have an associated fever 
and/or blood or mucus in the stool, and the diarrhea is felt to be due to the study 
medication you are taking, your doctor may prescribe anti-diarrhea medications such as 
loperamide  (imodium® 2 mg tablet).  You should take total of 4 mg of loperamide by 
mouth after the first unformed stool with 2 mg every 2 hours (4 mg every 4 hours while 
asleep), until resolution of episode for at least 12 hours (no more than 16 mg of 
loperamide during a 24-hour period).  
Instead of loperamide, your doctor may prescribe Lomotil (diphenoxylate HCl 2.5 mg + 
atropine sulfate 0.025 mg/tablet) 5 mg (2 tablets) 3 or 4 times daily (20 mg/24 hrs in 
divided doses is the maximum recommended dosage). 
If diarrhea does not improve, or you develop additional symptoms contact your 
study team.