Interim Abbreviated Clinical Study Report
Protocol C3661001

CLINICAL STUDY REPORT SYNOPSISSYNOPSIS
Study Title: Phase 1/2a Dose Escalation and Expansion Study Evaluating Safety,
Tolerability, Pharmacokinetic, Pharmacodynamics and Anti-Tumor Activity of PF-06873600
as a Single Agent and in Combination With Endocrine Therapy
Study Number: C3661001
Regulatory Agency or Public Disclosure Identifier Number:
US IND Number: 134457
ClinicalTrials.gov ID: NCT03519178
EudraCT Number: 2020-001757-40
Study Phase: 2aName of Study Intervention: Ebvaciclib (PF-06873600)
Name of Sponsor/Company: Pfizer Inc.
CSR Version and Report Date:
Document Version
Final CSR (PCD Date) Version 1.0

Report Date
28 November 2023

Number of Study Center(s) and Investigator(s):A total of 153 participants were enrolled and 151 participants were treated at 22 centers in
5 countries in this study.
A list of study centers and investigators involved in this study is provided inAppendix 16.1.4.1.
Publications: None.
Study Period:
Study Initiation Date (First Participant First Visit): 07 March 2018
Primary Completion Date: 05 April 2023
This study was neither discontinued nor interrupted.

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Rationale:
PF-06873600 is an inhibitor of cyclin-dependent kinases (CDK) 2, 4 and 6 that is being
investigated in women of any menopausal status and men with hormone receptor positive(HR+) human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic
breast cancer (mBCa) and patients with other tumor types that have potential to haveincreased Cyclin E expression/CDK2 activity, including locally recurrent/advanced ormetastatic triple negative breast cancer (TNBC) (women and men) and women withadvanced platinum resistant ovarian cancer.
This was the first-in-patient clinical study of PF-06873600. The study was divided into
2 parts: monotherapy dose escalation (Parts 1A and 1C) and then dose finding with
PF-06873600 immediate release (IR) formulation in combination with endocrine therapy(ET) (letrozole and fulvestrant [Ful]) (Part 1B) followed by dose expansion arms in
combination with ET (Part 2).
The purpose of this study was to assess the safety and tolerability of PF-06873600, as asingle agent (Parts 1A and 1C) and in combination with ET (Part 1B). In addition, thepreliminary antitumor activity of PF-06873600 was evaluated in patients with HR+ HER2mBCa in Part 2 (PF-06873600+Ful, 2A: post cyclin-dependent kinase 4/6 inhibitors[CDK4/6i]; 2C: CDK4/6i naïve/post ET), as well as the further confirmation of safety andtolerability of PF-06873600.
The study was terminated in September 2022 based on a strategic decision following thereview of clinical results within the current Pfizer oncology portfolio. This decision was notdue to any safety concerns or requests from any regulatory authorities. The safety profile for
PF-06873600 remained unchanged.

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Objectives, Endpoints, and Statistical Methods:
Parts 1A and 1C: Single Agent Dose Escalation and Part 1B: Combination Dose FindingType

Objective

Endpoints

Parts 1A and 1C:

Parts 1A, Part 1B, and Part 1C:

To assess the safety and tolerability of increasing dosesof PF-06873600 in patients with:

Dose-Limiting Toxicities (DLTs).

HR-positive HER2-negative advanced ormetastatic breast cancer (mBC) patients (third or
fourth line setting).



Locally recurrent/advanced or metastatic triple
negative breast cancer.

Adverse events (AEs) as characterizedby type, frequency, severity (asgraded by National Cancer InstituteCommon Terminology Criteria for
Adverse Events (NCI CTCAE version4.03), timing, seriousness, andrelationship to study therapy.

Advanced platinum resistant epithelial ovariancancer/fallopian tube cancer/primary peritoneal
cancerIn order to estimate the Maximum Tolerated Dose
(MTD) and select the Recommended Dose for
Expansion (RDE) for PF-06873600 as a single
agent (Part 1A and Part 1C only).

Laboratory abnormalities ascharacterized by type, frequency,
severity (as graded by NCI CTCAE
version 4.03), and timing.



Vital sign abnormalities.

Heart rate corrected QT interval (eg,
QTcF).

Primary
SafetyPart 1B:
To assess the safety and tolerability of PF-06873600 at
the single agent RDE in combination with letrozole
and in combination with fulvestrant (in a de-escalationmanner, if indicated) in patients with:HR-positive HER2-negative advanced or mBC(third or fourth line setting) in order to establish
the RDE for PF-06873600 in combination withletrozole and in combination with fulvestrant,
respectively.

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CLINICAL STUDY REPORT SYNOPSIS
Type

Objective

EndpointsPK parameters of PF-06873600:

SecondaryPharmacokinetics(PK)

Efficacypharmacodynamics (PD)To evaluate the single- and multiple- dose PK of
PF-06873600 when given as a single agent(Part 1A, and Part 1C), in combination withletrozole, and in combination with fulvestrant(Part 1B).

Single Dose (SD) - maximum
observed plasma concentration (Cmax),
time for Cmax (Tmax), area under theplasma concentration-time profile
from time 0 to the time of lastquantifiable concentration (AUClast),
and as data permitted, area under theplasma concentration-time profile
from time 0 extrapolated to infinity(AUCinf), apparent clearance (CL/F),
apparent volume of distribution(Vz/F), and terminal half-life (t½).

Multiple Dose (MD) (assuming steadystate was achieved)- steady state Cmax (Css,max), time forsteady state Cmax (Tss,max), steady statearea under the plasma concentrationtime profile within 1 dose interval(AUCss,), steady state lowest
observed concentration (Css,min),steady state apparent clearance(CLss/F), and as data permitted, steadystate volume of distribution (Vss/F),
t½, and observed accumulation ratio
based on AUC (Rac) (AUCss,/ singledose area under the plasma
concentration-time profile within 1
dose interval [AUCsd,]).



Objective Response (OR), as assessedusing the Response Evaluation
Criteria in Solid Tumors (RECIST)
version 1.1.

Time-to-event endpoints: eg, Durationof Response (DoR), Progression-Free
Survival (PFS), Time to Progression(TTP).

To evaluate the PD biomarkers of CDK pathway
modulation following treatment with
PF-06873600 in tumor.

Modulation of PD biomarkers (eg,phospho-retinoblastoma protein[pRb], Ki67) of CDK in tumor.

To explore the PD markers of CDK pathway
modulation following treatment with
PF-06873600 in surrogate tissue (ie, skin) andblood.



Modulation of PD biomarkers (eg,pRb, Ki67) of CDK in surrogate tissue(ie, skin), and in blood (thymidine
kinase 1 [TK1] activity).

To document any preliminary evidence ofanti-tumor activity of PF-06873600.

Exploratory*PD

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CLINICAL STUDY REPORT SYNOPSIS
Type

Objective

Endpoints

Biomarker



Genomic (gene alterations, including
mutation and copy number variation)and transcriptomic (ribonucleic acid
[RNA] expression and pathway genesignatures) characteristics in baseline
and post-treatment tumor biopsies andtheir relationship to clinical outcome.



Cell cycle and/or target-related
protein (eg, cyclin E1) expression intumor biopsies and their relationshipto clinical outcome.

Peripheral blood candidate biomarkers
consisting of deoxyribonucleic acid
(DNA), RNA or proteins that may berelated to response or resistance totreatment, including genetic
alterations (eg, phosphatidylinositol4,5-bisphosphate 3-kinase, catalytic
subunit alpha [PIK3CA], estrogen
receptor 1 [ESR1] mutations) incirculating tumor DNA, and theirrelationship to clinical outcome.



Biomarker

To explore biomarkers of sensitivity or resistanceto PF-06873600 in tumor tissue (archival and/orde novo tumor tissue).

To explore peripheral blood candidate biomarkers
of sensitivity or resistance to PF-06873600.

*These exploratory evaluations were not included for this terminated study.

Part 2: PF-06873600 Combination Dose Expansion
Type

Objective

Endpoints

EfficacyPreliminary antitumor activity measure for efficacy
included ORR, as assessed using RECIST 1.1.



Safety and tolerability:

SafetyIn combination (at the RDE from Part 1B) in
patients with:Primary
To evaluate the preliminary antitumor
activity and confirm the safety andtolerability of PF-06873600:

HR-positive/HER2-negative advanced
or mBC (PF-06873600 + fulvestrant) –(second or third line setting).

 AEs as characterized by type, frequency,
severity (as graded by NCI CTCAE v 4.03)
timing, seriousness and relationship to study
therapy.

HR-positive/HER2-negative advanced
or mBC (PF-06873600 + a nonsteroidal
aromatase inhibitor) (CDK4/6i naive).

 Lab abnormalities as characterized by type,
frequency, severity (as graded by NCI
CTCAE v 4.03) and timing.

HR-positive HER2-negative advanced
or mBC (PF-06873600+fulvestrant)(CDK4/6i naïve/post ET).

 Vital sign abnormalities.
 Heart rate corrected QT interval (eg, QTcF).

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Type

Objective

Endpoints

EfficacyTo further explore preliminary
antitumor activity of PF-06873600.



PK



To further evaluate the PK of
PF-06873600 in combination withletrozole, and in combination withfulvestrant at the respective RDE.

PK parameters of PF-06873600, including but notlimited to:SecondaryTime-to-event endpoints: eg, DOR, PFS, overall
survival (OS) and TTP.

SD - Cmax, Tmax.



MD (assuming steady state was achieved) - Css,max,Tss,max, Css,min and Rac,Cmax.



To evaluate PD biomarkers of CDK
pathway modulation following
treatment with PF-06873600 in
combination with fulvestrant or
letrozole in tumor.

Modulation of PD biomarkers (eg, pRb, Ki67) of
CDK in tumor.

PD

To explore pharmacodynamic (PD)markers of CDK pathway modulation
following treatment with PF-06873600
in combination with fulvestrant or
letrozole in surrogate tissue (ie, skin)and blood.

Modulation of PD biomarkers (pRb, Ki67) of CDK
in surrogate tissue (ie, skin), and in blood (TK1
activity).

BiomarkerTo explore biomarkers of sensitivity
and/or resistance to PF-06873600 intumor tissue (archival and de novo
tumor tissue).

Genomic (gene alterations, including mutation andcopy number variation) and transcriptomic (RNAexpression and pathway gene signatures)characteristics in baseline and post-treatment tumor
biopsies and their relationship to clinical outcome.



Cell cycle and/or target-related protein (eg, cyclin
E1) expressions in tumor biopsies and theirrelationship to clinical outcome.

Peripheral blood candidate biomarkers consistingof the DNA, RNA or proteins that may be related
to response or resistance to treatment, including
genetic alterations (eg, PIK3CA, ESR1 mutations)in circulating tumor DNA, and their relationship toclinical outcome.

PD

Exploratory*

BiomarkerTo explore peripheral blood candidate
biomarkers of sensitivity or resistance to
PF-06873600.

*These exploratory evaluations were not included for this terminated study.

Methodology:
This was a Phase 1/2a, open-label, multi-center, non-randomized, multiple dose study toevaluate safety, tolerability, PK, and PD of PF-06873600 administered as a single agent andthen in combination with ET.
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The overall study design was depicted in the schema below (Figure 1).
Figure 1. Overall Study Schema

Abbreviations: AI = aromatase inhibitor; Let = letrozole; LIC = Lead-in-Cohort; MR = modified release;
RP2D = recommended phase 2 dose.

Number of Participants (planned and analyzed):
Planned: Approximately 75 participants were planned to be enrolled in the dose
escalation/finding safety cohorts, and an additional 6-12 participants were expected in thebiomarker cohorts in Parts 1A and 1C.
In the dose expansion cohorts, approximately 100 participants (40, 30, and 30 in Parts 2A,
2B, and 2C, respectively) were expected to be enrolled in Part 2.
Analyzed: A total of 153 participants were assigned to treatment and 151 (98.7%) weretreated in the study.


In Part 1A, a total of 53 participants were assigned to treatment and 51 were treated.



In Part 1B, a total of 16 participants were assigned to treatment and treated.



In Part 1C, a total of 11 participants were assigned to treatment and treated.

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A total of 45 and 28 participants were assigned to treatment and treated in Part 2A
and Part 2C, respectively.

Diagnosis and Main Criteria for Inclusion and Exclusion:
Enrolled in this study were participants with HR+ HER2- advanced or mBC (histologicallyor cytologically proven). Participants with TNBC and ovarian cancer were included inParts 1A and 1C.
Study Interventions, Dose, Mode of Administration, and Batch Number(s):PF-06873600
PF-06873600 was administered orally twice a day (BID) (in 12 ±4 hour intervals) on acontinuous basis. Alternative intermittent dosing regimen was explored in part 1A (5 dayson/2 days off) and alternative modified release (MR) formulation dosing in Part 1C. A cycle
was defined as 28 days, regardless of missed doses or dose delays.
Letrozole
Letrozole was administered orally once daily (QD) continuously together with PF-06873600.
Fulvestrant
Fulvestrant 500 mg was administered intramuscularly into the buttocks slowly (1-2 minutes
per injection) as two 5 mL injections, one in each buttock.
The manufacturing lot numbers for the study interventions dispensed in this study areprovided in Table S1.

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Table S1. Study Intervention(s) Administered
Investigational Product
Description
Fulvestrant (2) Syringe Barrels @250mg/5 ml each syringe solution for
injection
Fulvestrant (2) Syringe Barrels @250mg/5 ml each syringe solution for
injection
Fulvestrant (2) Syringe Barrels @250mg/5 ml each syringe solution for
injection
Fulvestrant (Faslodex) 250 mg/5 mL
solution for Injection pre-filled
syringeLetrozole 2.5mg film-coated tablets

VendorLot No.

Pfizer Lot
No.

Strength/
Potency

Dosage Form

RE655

20-002296

50 mg/ml

Commercial
product

RJ319

20-AE-00083

50 mg/ml

Commercial
product

RX352

22-AE-00424

50 mg/ml

Commercial
product

RR367

21-AE-00226

50 mg/ml

Commercial
product

M2003757

20-002297

2.5 mg17-003913

1 mg

Commercial
product
Tablet19-002793

10 mg

Tablet20-002447

10 mg

Tablet19-002792

10 mg

Tablet19-004615

25 mg

Tablet21-DP-00442

25 mg

Tablet17-003915

25 mg

Tablet18-003627

25 mg

Tablet19-002795

40 mg

Tablet19-002794

40 mg

Tablet19-004614

5 mg

Tablet20-DP-00278

5 mg

Tablet17-003914

5 mg

TabletPF-06873600 1 mg Round White to
N/A
Off-White Tablet
PF-06873600 10 mg MR Tablet
19-000301 /(Long Duration)
19-001521
PF-06873600 10 mg MR Tablet
20-DP-00200(Long Duration)
PF-06873600 10 mg MR Tablet
19-000300 /(Short Duration)
19-001519
PF-06873600 25 mg Oval White to
19-DP-00092
Off-White Tablet
PF-06873600 25 mg Oval White to
21-000217
Off-White Tablet
PF-06873600 25 mg Oval White to
N/A
Off-White Tablet
PF-06873600 25 mg Oval White to
N/A
Off-White Tablet
PF-06873600 40 mg MR Tablet
19-000425 /(Long Duration)
19-001525
PF-06873600 40 mg MR Tablet
19-000424 /(Short Duration)
19-001523
PF-06873600 5 mg Round White to
19-DP-00093
Off-White Tablet
PF-06873600 5 mg Round White to
20-003985
Off-White Tablet
PF-06873600 5 mg Round White to
N/A
Off-White Tablet
Dosage form was solution for injection.
Dosage form was tablet.

Duration of Study Intervention:
Participants would receive PF-06873600 orally BID on a continuous basis in 28-day cycles.
Alternative intermittent dosing regimen was explored in Part 1A (5 days on/2 days off) and
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alternative MR formulation dosing in Part 1C. The plan was to continue treatment until
progression of disease, uncontrollable toxicity, a decision by the patient or investigator to
discontinue treatment or the study is terminated. It is estimated that each participant may
remain on treatment for approximately 6-8 cycles, making total study duration approximately
32-36 weeks.
Summary of Results:
Demographic and Other Baseline Characteristics:
Of 151 participants in the safety analysis set, all participants were female, with the majority
were White (71.5%). The median age was 59.0 years (range: 28, 84), and the median weightwas 70.400 kg (range: 42.50, 134.00). A total of 81 (53.6%) participants had baseline Eastern
Cooperative Oncology Group (ECOG) performance status (PS) 0, 69 (45.7%) baseline
ECOG PS 1, and 1 (0.7%) baseline ECOG PS as 2.
Of 151 participants in the safety analysis set in this study, 144 (95.4%) had the diagnosis ofbreast cancer and (136 [90.1%]) were HR+/HER2-; 5 (3.3%) participants had TNBC. Seven(4.6%) had the diagnosis of ovarian cancer. Cohorts 1B, 2A and 2C included mBCa
participants only.
Exposure:
The median duration of PF-06873600 treatment was 58.0 days (range: 5, 1093) in Part 1A; amedian of 2.0 cycles (range: 1, 36) were administered.
The median duration of PF-06873600 treatment was 125.5 days (range: 11, 419) in Part 1B; amedian of 5.0 cycles (range: 1, 15) were administered.
The median duration of PF-06873600 treatment was 112.0 days (range: 25, 466) in Part 1C; amedian of 4.0 cycles (range: 1, 16) were administered.
The median duration of PF-06873600 treatment was 120.0 days (range: 18, 636) in Part 2A;
a median of 5.0 cycles (range: 1, 23) were administered.
The median duration of PF-06873600 treatment was 148.5 days (range: 1, 413) in Part 2C; amedian of 5.5 cycles (range: 1, 15) were administered.
Efficacy Results:
Primary Efficacy Endpoint – Objective Response Rate in Part 2
A total of 67 participants were evaluable for OR in Part 2. A total of 8 (11.9%) participants
achieved PR.
In Part 2A (PF-06873600+Ful, HR+/HER2- mBCa post CDK4/6i), 3 participants achieved
OR (all PRs); the ORR was 6.7% (95% confidence interval [CI]: 1.4%, 18.3%).
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CLINICAL STUDY REPORT SYNOPSISIn Part 2C (PF-06873600+Ful, HR+/HER2- mBCa CDK4/6i naïve/post ET), 5 participants
achieved OR (all PRs); the ORR was 22.7% (95% CI: 7.8%, 45.4%).
Secondary Efficacy Endpoints - Duration of Response
The DoR for 1 confirmed responder in Part 2C was 5.8 months.
The other 7 confirmed responders were censored: 1 participant in Part 2A for start of new
anti-cancer therapy, 3 participants (2 in Part 2A and 1 in Part 2C) due to study being
terminated by sponsor, and 3 participants in Part 2C for being event free as of the cutoff date.
Secondary Efficacy Endpoints - Progression Free Survival
In Part 2A (PF-06873600+Ful, HR+/HER2- mBCa post CDK4/6i), among 45 participants infull analysis set, 27 had an event of disease progression. The estimated median PFS was 5.6
months (95% CI: 3.9, 7.8).
In Part 2C (PF-06873600+Ful, HR+/HER2- mBCa CDK4/6i naïve), among 28 participants infull analysis set, 8 had an event of disease progression or death. The estimated median PFS
was 11.1 months (95% CI: 7.5, not evaluable [NE]).
Secondary Efficacy Endpoints – Objective Response Rate in Part 1
In Part 1A, 1 participant achieved PR, treated at PF-06873600 IR 50 mg BID dose level.
In Part 1B, 1 participant achieved PR, treated with PF-06873600 IR 25 mg BID plus
fulvestrant combination.
In Part 1C, 1 participant achieved PR, treated with PF-06873600 IR 25 mg BID after two
20 mg MR lead-in doses.
Safety Results:
Because the frequency of certain medical events may be underestimated by reliance on asingle Medical Dictionary for Regulatory Activities (MedDRA) Preferred Term (PT), certain
PTs representing a similar medical event were analyzed in aggregate using Customized
Query (CQ) and represented throughout this clinical study report (CSR).
Of the 1385 all-causality treatment-emergent adverse events (TEAEs) reported in
147 (97.4%) participants across all cohorts, 832 events reported in 138 (91.4%) participants
were considered to be treatment-related.
The most frequently reported all-causality TEAEs (≥30% of participants) were nausea(62.9%), anaemia (CQ including anaemia, haemoglobin decreased, red blood cell countdecreased, haematocrit decreased, normochromic anaemia, normocytic anaemia andnormochromic normocytic anaemia) (44.4%), fatigue (CQ including asthenia, fatigue,
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tiredness and malaise) (43.7%), neutropenia (CQ including neutropenia, neutrophil countdecreased, neutrophil percentage decreased, cyclic neutropenia, agranulocytosis,
granulocytopenia and granulocyte count decreased) (37.7%), and vomiting (35.8%).
The most frequently reported treatment-related TEAEs (≥20% of participants) were nausea(60.9%), anaemia (CQ) (41.1%), fatigue (CQ) (39.7%), neutropenia (CQ) (37.1%), vomiting(33.8%), alopecia (27.8%), leukopenia (CQ including leukopenia and white blood cell countdecreased) (24.5%), and headache (21.2%).
A total of 34 (22.5%) participants had all-causality serious adverse events (SAEs) reported.
The most frequently reported all-causality SAEs were febrile neutropenia (5 [3.3%]
participants), abdominal pain, colitis, and hypotension (each in 3 [2.0%] participants).
A total of 13 (8.6%) participants had treatment-related SAEs reported. The most frequently
reported treatment-related SAEs were febrile neutropenia (5 [3.3%] participants) followed byneutropenia (CQ), colitis, and stomatitis (each in 2 [1.3%] participants).
A total of 69 (45.7%) participants had maximum Grade 3-4 all-causality TEAEs, and54 (35.8%) participants had maximum Grade 3-4 treatment-related TEAEs.
A total of 19 (12.6%) deaths reported as of primary completion date (PCD). Five (3.3%)
deaths were reported on treatment (while receiving study treatment or within 28 days after
last dose of study treatment or start of new anti-cancer therapy minus 1 day, whicheveroccurred first). Grade 5 TEAE of cardiac arrest was reported in 2 (1.3%) participants; Grade
5 TEAEs of death, disease progression, gastrointestinal bacterial infection, haemolysis, andrespiratory failure were each reported in 1 (0.7%) participant.
A total of 2 (1.3%) participants reported treatment-related Grade 5 TEAEs. Grade 5
treatment-related TEAEs of cardiac arrest and gastrointestinal bacterial infection were eachreported in 1 (0.7%) participant.
Dose-Limiting Toxicity
In Part 1A, a total of 6 (9.4%) participants had DLTs reported.
Two participants in PF-06873600 35 mg BID cohort had DLTs:

One participant had Grade 4 neutrophil count decreased, considered treatment-related.

One participant had Grade 4 neutrophil count decreased and Grade 4 platelet countdecreased, both AEs considered treatment-related.

Four participants in PF-06873600 50 mg BID cohort had DLTs:

One participant had Grade 4 febrile neutropenia, considered treatment-related.
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One participant had Grade 3 fatigue, considered treatment-related.

One participant had Grade 4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 5
cardiac arrest, and Grade 4 multiple organ dysfunction syndrome, all consideredtreatment-related.

One participant had Grade 3 febrile neutropenia and Grade 3 colitis, both AEs consideredtreatment-related.

Clinical Laboratory Evaluation
A total of 13 (8.7%) participants across all cohorts reported Grade 4 neutrophil countdecreased, 6 (4.0%) reported Grade 4 white blood cell decreased, 3 (2.0%) reported Grade 4
platelet count decreased, and 1 (0.7%) reported Grade 4 lymphocyte count decreased, all ofwhom had grade increased compared to baseline.
Except Grade 4 hypophosphatemia reported in 2 (1.4%) participants, Grade 4 blood bilirubinincreased, hypercalcemia, hyperkalemia, and lipase increased, were each reported in single
participant, all of whom had grade increased compared to baseline.
Vital Signs
For systolic blood pressure, 9 (6.0%) participants had values <90◦mm◦Hg, 15 (10.0%) withincreases ≥30◦mm◦Hg, and 26 (17.3%) with decreases ≥30◦mm◦Hg.
For diastolic blood pressure, 7 (4.7%) participants had values <50◦mm◦Hg, 15 (10.0%) withincreases ≥20◦mm◦Hg, and 24 (16.0%) with decreases ≥20◦mm◦Hg.
For heart rate, 1 (0.7%) participant had value <40 bpm, and 6 (4.0%) participants had values>120 bpm.
Electrocardiograms
For PR interval, 1 (0.7%) participant had change from baseline ≥25% and baseline value>200 msec, and 1 (0.7%) with change from baseline ≥50% and baseline value ≤200 msec.
For QRS interval, 1 (0.7%) participant had change from baseline ≥25% and baseline value>100 msec, and 1 (0.7%) with change from baseline ≥50% and baseline value ≤100 msec.
For QTcF, 44 (29.1) participants had values ≥450 - ≤480 msec, 3 (2.0%) with values ≥481 ≤500 msec, 2 (1.3%) with values ≥501 msec, 24 (15.9%) with change from baseline >30 ≤60 msec, and 4 (2.6%) with change from baseline >60 msec.

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Pharmacokinetic Results:
Following oral administration of the IR formulation, PF-06873600 was rapidly absorbed,
with median Tmax values of 1 to 4 hours after the first dose. The geometric mean PK
parameters of PF-06873600, including Cmax, Cmin, and AUC, in general, increased with dose
up to at least 35 mg BID. There was minimal accumulation following repeated BID dosing,with geometric mean Rac ranging from 0.7 to 1.3. The arithmetic mean t½ ranged from 2 to
3 hours. PF-06873600 exposure exhibited moderate to high inter-participant variability. At
25 mg BID, the geometric mean coefficient of variation percentage (CV%) values were 58%
and 56% for single dose AUCinf and Cmax, respectively. After multiple dosing at 25 mg BID,
the geometric mean CV% values were 45%, 43% and 119% for AUCtau, Cmax and Cmin,
respectively.
The plasma exposures of PF-06873600 were largely comparable between monotherapy andcombination therapy with fulvestrant or letrozole.
Pharmacodynamic Results:
Following PF-06873600 IR 25 mg BID monotherapy in Part 1A, the median change in Ki67
positive cells was -11.67%, and the median change in pRb H-score was -16.49.
Following PF-06873600 IR 25 mg BID / fulvestrant combination treatment in Part 1B andPart 2A, the median change in Ki67 positive cells was -35.90%, and the median change inpRb H-score was -31.88.
Conclusions:PF-06873600 has been evaluated at doses from 1 mg to 50 mg BID during the dose
escalation part (Part 1). PF-06873600 exposures were generally increased with dose up to atleast 35 mg BID with moderate to high inter-participant variability. Based on Part 1A andPart 1B safety and PK data, 25 mg BID (IR formulation) was chosen as the recommended
dose for monotherapy and in combination with ET (letrozole and fulvestrant). Most
frequently reported all grades TEAE, as well as most frequently observed Grade 3-4 TEAE,
SAE, DLT and AE leading to dose reduction and discontinuation, were neutropenia andgastrointestinal AEs.
PF-06873600 demonstrated modest anti-tumor activity as monotherapy: 1 PR was observed
at PF-06873600 IR 50 mg BID dose level (Part 1A), and 1 PR in MR selection cohort MR
20 mg/IR 25 mg BID (Part 1C).
In dose expansion cohorts, PF-06873600 demonstrated early signs of efficacy in combination
with fulvestrant: 3 PRs were observed (ORR of 6.7% [95% CI: 1.4%, 18.3%]) in Part 2A(PF-06873600+Ful, HR+/HER2- mBCa post CDK4/6i), and 5 PRs were observed (ORR of
22.7% [95% CI: 7.8%, 45.4%]) in Part 2C (PF-06873600+Ful, HR+/HER2- mBCa CDK4/6inaïve/post ET).
In conclusion, PF-06873600 demonstrated overall favorable benefit risk profile consistent
with CDK4/6 inhibitors class of drugs, as well as some clinical activity in mBC HR+/HER2PFIZER CONFIDENTIAL
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Interim Abbreviated Clinical Study Report
Protocol C3661001

CLINICAL STUDY REPORT SYNOPSIS
mBC. Nevertheless, the totality of the PK, safety, and efficacy data do not support thetransformational profile needed to justify further clinical development along a path toregistration.
The Phase 1 study C3661001 was terminated by Sponsor based on a business strategic
decision.

PFIZER CONFIDENTIAL
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