MATCH Treatment Subprotocol Z1C: Phase II Study of Palbociclib (PD-0332991) in Patients With Tumors With CDK4 or CDK6 Amplification
Phase: PHASE2
Conditions: Advanced Lymphoma, Advanced Malignant Solid Neoplasm, Refractory Lymphoma, Refractory Malignant Solid Neoplasm
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
August 19, 2020
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 #25 to EAY131-Z1C, MATCH Treatment Subprotocol Z1C: Phase II 
Study of Palbociclib (PD-0332991) in Patients with Tumors with CDK4 or CDK6 Amplification. 
This addendum is in response to a Request for Rapid Amendment for Palbociclib from Dr. 
Charles Kunos dated November 19, 2019, and also, Dr. Tali Johnson’s Amendment Request for 
updates to specific protocol language for Palbociclib dated June 5, 2020. 
Please replace your current copy of the protocol and Informed Consent document with these 
updated versions. 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. Local IRB review and approval is unnecessary.
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permitted to conduct the study utilizing outdated versions of any MATCH protocol documents 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.
Re: Review of Amendment #36 of Protocol #EAY131-Z1C: “MATCH Treatment Subprotocol 
Z1C: Phase II Study of Palbociclib (PD-0332991) in Patients with Tumors with CDK4 or CDK6 
Amplification.” The following are ECOG-ACRIN’s responses to the CTEP review comments 
dated 5/26/2020. Please note that the Principal Investigator’s comments appear in bold below.
I.
Comments Requiring a Response– Administrative & Editorial Issues:
#
Section
Comments
1.
ICD – “Why is this 
study being done?”
Under Why is this study being done? on page 1, please change 
the target accrual back to 49, consistent with protocol amendment 
#35:
There will be about 35 49 people taking part in this study.
PI Response:   Thank you. This has been corrected to reflect 
the approved accrual expansion to 49 patients.

 
ii 
II. Recommendations: 
# 
Section Comments 
2. 
3.2.1 
The Summary of Changes state that, “In second box, under “Pregnancies” 
revised language referencing “subject” to “female patient,” however this 
change does not appear to have been made.  Please revise the section below 
accordingly. 
EAY131 – Subprotocol Z1C 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 subject is on palbociclib, or within 28 days of the subject’s last dose 
of palbociclib, 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. 
PI Response: Thank you. This has been corrected.  
III. Company Comments – Requiring a Response:  
# 
Section Comments 
3. 
3.4 
We noticed that pneumonitis was added as ADR but in the section of the dose 
modification guidelines and Grade 4 event, the language would allow for 
treatment to be resumed at the lower dose, which does not align with our 
recommendations to permanently discontinue palbociclib with severe ILD or 
pneumonitis.  
PI Response: Thank you. We’ve revised the language to discontinue 
pablociclib for Grade 4 non-hematologic toxicity for pneumonitis or ILD.  
II. 
Additional Protocol Changes by Principal Investigator: 
 
The following revisions to the EAY131-Z1C protocol have been made in this addendum: 
 
Section 
Change 
1. 
Cover Page 
Updated Version Date and addendum number. 
2. 
3.2.1 
In second box, under “Pregnancies” revised language referencing 
“subject” to “female patient”.  
3. 
3.3 
Updated the Palbociclib CAEPR to Version 2.4 September 13, 
2019.  
4. 
Appendix III 
Updated patient drug information template format. 

 
iii 
The following revisions to the EAY131-Z1C Informed Consent Document have been made in 
this addendum: 
 
Section 
Change 
1. 
Page 1 
Updated Version Date. 
2. 
Possible Side 
Effects Palbociclib 
Updated the condensed risk list for Palbociclib to Version 2.4, 
September 13, 2019.  
If you have any questions regarding this addendum, please contact aaagu@ecog-acrin.org or 
857-504-2900. 
We request review and approval of this addendum to EAY131-Z1C so ECOG-ACRIN may 
activate it promptly.   
Thank you.  
Sincerely, 
Pamela Cogliano 
Senior Director of Protocol Development 
 
 

EAY131-Z1C
1
Molecular Analysis for Therapy Choice (MATCH)
MATCH Treatment Subprotocol Z1C: Phase II Study of 
Palbociclib (PD-0332991) in Patients with Tumors with 
CDK4 or CDK6 Amplification
PALBOCICLIB TREATMENT SUBPROTOCOL
CHAIR:
Mark O’Hara, MD
PALBOCICLIB TREATMENT SUBPROTOCOL
CO-CHAIR:
Mark Dickson, MD
PALBOCICLIB TRANSLATIONAL CHAIR:
Angela DeMichele, MD, MSCE
Version Date: August 19, 2020
NOTE: This subprotocol (EAY131-Z1C) 
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 #24
Addendum #25
Agent
IND#
NSC#
Supply
Palbociclib
IND Sponsor: DCTD, NCI IND#: 
772256
NCI Supplied

ECOG-ACRIN 
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Cancer Research Group 
Version Date: August 19, 2020 
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Table of Contents 
Molecular Analysis for Therapy Choice (MATCH) ...................................................... i 
MATCH Treatment Subprotocol Z1C: Phase II Study of Palbociclib (PD-0332991) in 
Patients with Tumors with CDK4 or CDK6 Amplification .................................... 1 
Table of Contents ...................................................................................................... 2 
Schema ...................................................................................................................... 4 
1. Introduction ........................................................................................................ 5 
1.1 
Palbociclib ................................................................................................. 5 
1.2 
Supporting Preliminary Data ..................................................................... 6 
1.3 
Arm Expansion .......................................................................................... 8 
2. Selection of Patients ........................................................................................... 9 
2.1 
Registration to Treatment ......................................................................... 9 
3. Palbociclib 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 
Palbociclib (PD-0332991, NSC 772256) ................................................... 14 
3.4 
Dose Modifications ................................................................................. 17 
3.5 
Supportive Care ....................................................................................... 18 
3.6 
Duration of Agent-specific treatment ..................................................... 18 
3.7 
Duration of Follow-Up ............................................................................. 18 
4. Study Parameters .............................................................................................. 19 
4.1 
Therapeutic Parameters for Palbociclib Treatment ................................ 19 
5. Drug Formulation and Procurement ................................................................. 21 
5.1 
Palbociclib (PD-0332991) (NSC 772256) ................................................. 22 
6. Translational Studies ......................................................................................... 24 
7. References ........................................................................................................ 24 
Appendix I  Patient Pill Calendar ............................................................................. 26 
Appendix II  Actionable Mutations for Sub-Protocol EAY131-Z1C .......................... 28 
Appendix III  PATIENT CLINICAL TRIAL WALLET CARD ............................................. 29 
 
 
 
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3 
TREATMENT SUBPROTOCOL CHAIR 
Mark O’Hara, MD 
Perelman School of Medicine 
University of Pennsylvania 
3400 Civic Center Blvd, 7 South Tower 
Philadelphia, PA. 19104 
Phone #: 215-615-0735 
Fax #: 215-615-4949 
Email: Mark.ohara@uphs.upenn.edu 
 
TREATMENT SUBPROTOCOL CO-CHAIR  
Mark Dickson, MD 
Memorial Sloan Kettering Cancer Center 
300 E 66th St 
New York, NY 10065 
Phone #: (646) 888-4164 
Fax #: (646) 888-4251 
Email: dicksonm@mskcc.org 
 
TRANSLATIONAL CHAIR 
Angela DeMichele, MD, MSCE 
Perelman School of Medicine 
University of Pennsylvania 
3400 Civic Center Blvd, 3W PCAM 
Philadelphia, PA. 19104 
Phone #: 215-614-1850 
Fax #: 214-615-3349 
Email: Angela.DeMichele@uphs.upenn.edu 
 
 

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Version Date: August 19, 2020 
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Schema 
 
 
Long-Term Follow-Up
Palbociclib 125mg by mouth 
daily on days 1-21 on a 28 
day cycle
Until Progression
Cycle = 28 days
Accrual Goal: 49
 

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1. Introduction 
1.1 
Palbociclib 
1.1.1 
Background 
Cell cycle dysregulation is a hallmark of most common malignancies, 
including mutations in cyclin/cyclin-dependent kinase (cdk) 
components, gene amplification of regions of the genome that encode 
cyclins and cdks, overexpression of individual proteins that relate to 
cell cycle proteins, or inactivation of the key proteins that serve as 
regulated inhibitors of the cell cycle. As a consequence of these 
alterations, cells adopt a proliferative program. In the G1 to S 
transition, cyclin D proteins associate with Cdk4 or Cdk6 to form an 
activating complex that catalyzes phosphorylation of the tumor 
suppressor retinoblastoma protein (Rb), which in turn allows for the 
subsequent activation of the E2F-dependent transcription.  
Palbociclib is a highly selective, reversible oral inhibitor of CDK 4 and 
6. Preclinical studies show that palbociclib reversibly arrests cancer 
cells in G1, preventing progression to S phase, through reduction of 
Rb phosphorylation at CDK4/6-specific sites. This inhibition results in 
accumulation of Rb positive tumor cells in G1, down regulation of 
genes regulated by E2F, reduction of Ki-67, and tumor regression (1).  
Two phase 1 studies evaluating differing dosing schedules of 
palbociclib were completed. The first phase 1 study tested increasing 
doses of palbociclib on a two week on, one week off schedule (2/1) 
and determined that the maximum tolerated dose was 200mg daily 
(2). The second study evaluated a three week on, one week off 
schedule (3/1) and determined the 125mg daily dose to be the 
recommended phase 2 dose (3). Both phase 1 studies show that 
palbociclib is well tolerated with the main toxicity of myelosuppression. 
The 125mg dose given on 3/1 schedule is the dosing schedule that 
was moved into phase II and III studies of palbociclib given a reliable 
safety profile and efficacy, and therefore is the dose used in this 
study.  
1.1.2 
Pharmacokinetics 
In plasma collected from patients enrolled on the Phase I trials above, 
palbociclib concentrations were detectable 1 hour following oral 
administration, but was slowly absorbed with a median time of 
maximum concentration of 4-7 hours and slowly eliminated with a 
median elimination half-life of 26-26.7 hours (2, 3). This demonstrates 
appropriateness of the daily dosing schedule. Furthermore, the 
geometric mean volume of distribution was significantly greater than 
total body water, indicating extensive distribution to peripheral tissues 
(2, 3). Extended PK analyses are not available; however the 
reproducible toxicity of the drug over long-term dosing indicates that 
drug accumulation is unlikely. Metabolism is the major route of 
elimination of palbociclib, with excretion in stool and urine playing a 
minimal role.  

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1.1.3 
Toxicity 
Palbociclib has a consistent side effect profile across a multitude of 
studies. Neutropenia is the most common grade 3 or 4 adverse 
events, occurring in approximately 35-54% of patients receiving single 
agent palbociclib, though only 2.7-3.3% of patients experienced febrile 
neutropenia (4-6). Other grade 3 or 4 hematologic toxicities occur less 
frequently, including thrombocytopenia in 19-30% and anemia in 5-
13%. Non-hematologic toxicities include fatigue (10-14%), nausea (5-
12%), and diarrhea (3.3-6%) (4-6).  
1.1.4 
Efficacy 
Palbociclib has been evaluated both as a single agent and in 
combination with hormone therapy in breast cancer. In the Phase I 
study noted above examining single agent palbociclib on the 3/1 
schedule, patients with RB+ liposarcoma, renal cell, germ cell tumor, 
breast cancer, thymoma, appendiceal and ovarian cancer all achieved 
stable disease for at least 4 months (3). In the phase I study 
examining 2/1 schedule, one patient with RB+ testicular cancer had a 
partial response (2). A pharmacodynamic study of palbociclib in 
patients with RB+ mantle cell lymphoma harboring the translocation 
t(11;14), resulting in increased cyclin D1 activity, demonstrated a 65% 
disease control rate (6). Another phase II study in patients with CDK4-
amplified liposarcoma revealed a 66% progression free survival at 12 
weeks (4). In a heavily pretreated metastatic breast cancer 
population, the clinical benefit rate was 19% (5). The addition of 
palbociclib to letrozole in the first line metastatic setting doubled the 
progression free survival (PFS) from 10.2 months in the letrozole 
alone arm to over 20 months in the combination (7). It was with this 
data that palbociclib received accelerated approval from the FDA. 
Moreover, when combined with fulvestrant, another anti-hormone 
therapy used to treat patients with metastatic ER+ breast cancer who 
had progressed on one line of endocrine therapy and/or 
chemotherapy, the addition of palbociclib improves the PFS from 3.8 
months with fulvestrant alone to 9.2 months with the combination (8). 
Thus, palbociclib can be used for the treatment of ER+ metastatic 
breast cancer in the first line and beyond.   
1.2 
Supporting Preliminary Data  
1.2.1 
CDK 4 and CDK6 amplification 
Aberrations of Cdk4, Cdk6, and cyclin D, all found with varying 
frequencies across malignancies, are associated with increased 
cellular proliferation. More specifically, as demonstrated in the TCGA 
and other databases, amplification of CDK4 or CDK6 is noted in a 
variety of cancers and has been correlated with overexpression and 
increased cellular proliferation in cancer tissues (see Table 1) (9-14). 

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Version Date: August 19, 2020 
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Table 1 
Tumor Type 
Cases of 
amplified 
CDK6 (%) 
Cases of 
amplified 
CDK4 (%) 
Esophageal carcinoma 
13% 
 
Gastric adenocarcinoma 
7.3% 
4% 
Head and neck squamous cell carcinoma 
7.2% 
<1% 
Pancreatic adenocarcinoma 
5.5% 
3-6% 
Lung squamous cell carcinoma 
5.6% 
 
Bladder urothelial carcinoma 
3.9% 
2% 
Prostate adenocarcinoma 
3.6% 
5% 
Lung adenocarcinoma 
3.5% 
7% 
Glioblastoma multiforme 
3.3% 
16-18.5% 
Hepatocellular carcinoma 
2.6% 
 
Sarcoma 
3%  
18-24% 
CDK4 and CDK6 frequencies from cBIOPortal (13) 
1.2.2 
Rationale for Palbociclib in CDK4 and CDK6 amplified tumors 
1.2.2.1 
Preclinical Studies 
Though CDK4 or CDK6 amplification is relatively common 
and has oncogenic properties (15), studies targeting CDK4 
or CDK6 amplification are limited. Preclinical studies of 
CDK4/6 inhibition have shown specific inhibition of both 
Cdk6 and Cdk6- and Cdk4-induced Rb phosphorylation, 
leading to decreased cell cycle proliferation (16, 17). 
Furthermore, Barton KL et al demonstrate sensitivity to 
PD-0332991 (palbociclib) in a brainstem glioma mouse 
model with CDK4 amplification (18). Moreover, in Zhang 
YX et al, CDK4-amplified liposarcoma demonstrated 
significant sensitivity to LEE011, another CDK4/6/ inhibitor, 
in cell lines and in mouse xenograft assays (14). CDK6 
was overexpressed in rhabdomyosarcoma cell lines that 
were sensitive to LEE011 (19), and CDK4 and CDK6 
amplified pancreatic neuroendocrine xenografts (20) and 
glioblastoma cell lines with CDK6 amplification were 
sensitive to inhibition by palbociclib (21). 
1.2.2.2 
Clinical Studies 
Palbociclib has been evaluated in phase II studies in CDK4 
amplified liposarcoma. While the response rates in 
published reports of palbociclib are relatively low at 3% as 
a single agent in this population progression free survival is 
enhanced, demonstrating a 66% 3 month progression free 
survival rate (4), with median progression free survival 
ranging from 18-24 weeks depending on dosing schedule 
(22) and 35-40% 6 month progression free survival rate on 
the 3 week on, 1 week off schedule (pending publication). 

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To the best of our knowledge, there are no clinical studies 
in patients with CDK6 amplified tumors with a CDK4/6 
inhibitor. However, as noted above in the preclinical 
studies, palbociclib has shown beneficial effect in this 
pathway.  
1.3 
Arm Expansion 
1.3.1 
In some circumstances, it may necessary to expand a treatment arm if 
an inadequate number of assays from Designated Laboratories can 
be confirmed by the central Oncomine® Assay to ensure 31 evaluable 
patients for the primary endpoint. In those circumstances, the study 
will be expanded to achieve a total of 35 patients, i.e. the number of 
cases to allow for attrition so that at least 31 patients are evaluable for 
the primary endpoint. An additional 14 patients will be accrued in this 
expansion, i.e. expanded from 35 to 49. If planned accrual is not 
completed within 21 months, the expansion cohort will be closed to 
further accrual. 
 
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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 CDK4 amplification or CDK6 amplification, 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. 
2.1.3 
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:  _______________ 
2.1.4 
Patients must not have breast cancer, mantle cell lymphoma, 
myeloma, or liposarcoma. 
2.1.5 
Patients must not have known hypersensitivity to palbociclib or 
compounds of similar chemical or biologic composition. 
_____ 
_____ 
_____ 
_____ 
_____ 
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2.1.6 
Patients with known or symptoms of left ventricular dysfunction will be 
excluded. 
2.1.7 
Patients must not have received prior therapy with a CDK4 or CDK6 
inhibitor (including but not limited to palbociclib, abemaciclib, or 
ribociclib). 
2.1.8 
Patients must not be using drugs or foods that are known potent 
CYP3A4 inhibitors or inducers, or are CYP3A substrates with narrow 
therapeutic indices (See Appendix III of this subprotocol). 
 
 
 
 
 
Physician Signature 
 
Date 
OPTIONAL: 
This signature line is provided for use by institutions wishing to 
use the eligibility checklist as source documentation. 
 
 
_____ 
_____ 
_____ 

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3. 
Palbociclib Treatment Plan 
3.1 
Administration Schedule 
3.1.1 
Palbociclib 125 mg, by mouth with food once daily on days 1-21 of the 
28 days cycle (3 weeks on, 1 week off) 
Repeat 28 day cycles until progression. 
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 Z1C 
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 Z1C specific expedited reporting 
requirements: 
x 
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 
palbociclib, or within 28 days of the female patient’s last dose 
of palbociclib, 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. 
 
EAY131 – Subprotocol Z1C specific expedited reporting 
exceptions: 
For Subprotocol Z1C, the adverse events listed below do not 
require expedited reporting via CTEP-AERS: 
x 
If an AE meets the reporting requirements of the protocol, and 
it is listed on the SPEER, it should ONLY be reported via 
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CTEP-AERS if the grade being reported exceeds the grade 
listed in the parentheses next to the event. 
3.2.2 
Other recipients of adverse event reports and supplemental data 
DCTD/NCI will notify ECOG-ACRIN/pharmaceutical collaborator(s) of 
all AEs reported to the FDA. Any additional written AE information 
requested by ECOG-ACRIN MUST be submitted to BOTH the NCI 
and ECOG-ACRIN. 
Adverse events determined to be reportable via CTEP-AERS must 
also be reported by the institution, according to the local policy and 
procedures, to the Institutional Review Board responsible for oversight 
of the patient. 
3.2.3 
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 
x 
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. 
x 
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. 

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NOTE: 
If a patient has been enrolled in more than one NCI-
sponsored study, the Second Primary Form must be 
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. 

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3.3 
Comprehensive Adverse Events and Potential Risks List (CAEPR) for Palbociclib 
(PD-0332991, NSC 772256) 
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 1751 patients. 
Below is the CAEPR for Palbociclib (PD-0332991). 
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 in the SPEER. 
Version 2.4, September 13, 20191 
Adverse Events with Possible 
Relationship to Palbociclib (PD-0332991) 
(CTCAE 5.0 Term) 
[n= 1751] 
 
Specific Protocol 
Exceptions to Expedited 
Reporting 
(SPEER) 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)  
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
  
Anemia 
 
 
 Anemia (Gr 2) 
 
 
Febrile neutropenia 
  
EYE DISORDERS 
  
 
Blurred vision 
 
  
 
Dry eye 
 
  
 
Watering eyes 
 
  
GASTROINTESTINAL DISORDERS 
  
 
Constipation 
 
 Constipation (Gr 2) 
 
Diarrhea 
 
 Diarrhea (Gr 2) 
 
Mucositis oral 
 
 Mucositis oral (Gr 2) 
Nausea 
 
 
 Nausea (Gr 2) 
 
Vomiting 
 
 Vomiting (Gr 2) 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
  
Fatigue 
 
 
 Fatigue (Gr 2) 
 
Fever 
 
  
INFECTIONS AND INFESTATIONS 
  
Infection2 
 
 
 Infection2 (Gr 2) 
INVESTIGATIONS 
  
 
Alanine aminotransferase 
increased 
 
  
 
Aspartate 
aminotransferase 
increased 
 
  
 
Lymphocyte count 
decreased 
 
 Lymphocyte count 
decreased (Gr 2) 
Neutrophil count decreased  
 
 Neutrophil count 
decreased (Gr 2) 
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Adverse Events with Possible 
Relationship to Palbociclib (PD-0332991) 
(CTCAE 5.0 Term) 
[n= 1751] 
 
Specific Protocol 
Exceptions to Expedited 
Reporting 
(SPEER) 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%)  
 
 
Platelet count decreased 
 
 Platelet count decreased 
(Gr 2) 
White blood cell decreased  
 
 White blood cell decreased 
(Gr 2) 
METABOLISM AND NUTRITION DISORDERS 
  
 
Anorexia 
 
 Anorexia (Gr 2) 
NERVOUS SYSTEM DISORDERS 
  
 
Dysgeusia 
 
  
 
Headache3 
 
  
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
  
 
Epistaxis 
 
  
 
 
Pneumonitis 
  
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
  
 
Alopecia 
 
 Alopecia (Gr 2) 
 
Dry skin 
 
  
 
Skin and subcutaneous 
tissue disorders - Other 
(rash)4 
 
  
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 Infection includes all 75 infection sites under the INFECTIONS AND INFESTATIONS SOC. 
3 Headache has been observed in trials using Palbociclib (PD-0332991) in combination with fulvestrant. 
4 Rash includes rash, rash maculo-papular, erythema, erythematous rash, erysipelas, rash pruritic, rash 
papular, generalized rash, exanthema, allergic dermatitis, dermatitis acneiform, and dermatitis. 
5 Peripheral neuropathy includes both peripheral motor neuropathy and peripheral sensory neuropathy 
under the NERVOUS SYSTEM DISORDERS SOC. 
Adverse events reported on palbociclib (PD-0332991) trials, but for which there is 
insufficient evidence to suggest that there was a reasonable possibility that palbociclib 
(PD-0332991) caused the adverse event: 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Bone marrow hypocellular; Blood and 
lymphatic system disorders - Other (pancytopenia) 
CARDIAC DISORDERS - Atrial fibrillation; Cardiac arrest; Cardiac disorders - Other 
(paroxysmal atrial fibrillation with rapid ventricular response); Palpitations; Pericarditis; Sinus 
bradycardia; Supraventricular tachycardia 
EYE DISORDERS - Cataract; Eye disorders - Other (retinal hemorrhage) 
GASTROINTESTINAL DISORDERS - Abdominal distension; Abdominal pain; Ascites; Colitis; 
Colonic perforation; Dry mouth; Dyspepsia; Dysphagia; Esophageal stenosis; Flatulence; 
Gastric hemorrhage; Gastrointestinal disorders - Other (gastrointestinal hemorrhage); Intra-
abdominal hemorrhage; Lower gastrointestinal hemorrhage; Small intestinal obstruction; Small 
intestinal perforation; Upper gastrointestinal hemorrhage 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - Chills; Death NOS; 
Edema limbs; Localized edema; Malaise; Non-cardiac chest pain; Pain; Sudden death NOS 

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HEPATOBILIARY DISORDERS - Hepatic failure; Hepatobiliary disorders - Other (bile duct 
obstruction); Hepatobiliary disorders - Other (jaundice) 
IMMUNE SYSTEM DISORDERS - Allergic reaction 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS - Fall; Fracture 
INVESTIGATIONS - Alkaline phosphatase increased; Blood bilirubin increased; CPK increased; 
Creatinine increased; Ejection fraction decreased; GGT increased; INR increased; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Dehydration; Hypercalcemia; Hyperglycemia; 
Hyperkalemia; Hypermagnesemia; Hyperuricemia; Hypoalbuminemia; Hypocalcemia; 
Hypokalemia; Hyponatremia; Hypophosphatemia; Metabolism and nutrition disorders - Other 
(failure to thrive) 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Arthralgia; Back pain; 
Flank pain; Generalized muscle weakness; Muscle cramp; Musculoskeletal and connective 
tissue disorder - Other (osteomyelitis); Myalgia; Neck pain; Osteonecrosis; Pain in extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL. CYSTS AND POLYPS) - 
Treatment related secondary malignancy 
NERVOUS SYSTEM DISORDERS - Dizziness; Dysesthesia; Dysphasia; Intracranial 
hemorrhage; Nervous system disorders - Other (peripheral neuropathy)5; Syncope 
PSYCHIATRIC DISORDERS - Confusion; Insomnia; Psychiatric disorders - Other (altered 
mental status) 
RENAL AND URINARY DISORDERS - Acute kidney injury; Hematuria 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - Cough; Dyspnea; Hypoxia; 
Oropharyngeal pain; Pleural effusion; Postnasal drip; Pulmonary edema; Pulmonary 
hypertension 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Hyperhidrosis; Pruritus 
VASCULAR DISORDERS - Hypertension; Hypotension 
NOTE: 
Palbociclib (PD-0332991) 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. 
 

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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). 
 
Dose Level 
Palbociclib Dose 
1 
125 mg PO QD 
-1 
100 mg PO QD 
-2 
75 mg PO QD 
Discontinuation of palbociclib for more than 2 weeks (excluding rest days) 
will result in the removal of the patient from the study. 
Table 2: Hematologic Toxicities: Dose Modification and Management for 
Day 1 of all Cycles and Day 14 of Cycles 1 and 2. 
CTCAE Grade 
Dose Modification 
Grade 1 or 2 
No dose adjustment is required. 
Grade 3 
Day 1 of all Cycles: 
Withhold palbociclib, repeat complete blood count 
monitoring in 1 week. When recovered to Grade ≤ 2, start 
the next cycle at the same dose 
 
Day 14 of Cycles 1 and 2: 
Continue palbociclib at current dose to complete cycle. 
Repeat complete blood count on Day 21.  
Consider dose reduction in cases of prolonged (> 1 week) 
recovery from Grade 3 neutropenia or recurrent Grade 3 
neutropenia in subsequent cycles 
Grade 3 + Fever ≥ 38.5 
and/or infection 
Withhold palbociclib and initiation of next cycle until 
recovery to Grade ≤ 2. 
Resume at next lower dose. 
Grade 4 
Withhold palbociclib and initiation of next cycle until 
recovery to Grade ≤ 2. 
Resume at next lower dose. 
Table 3: Non-hematologic Toxicities: Dose Modification and Management 
for Day 1 of all Cycles 
CTCAE Grade 
Dose Modification 
Grade 1 or 2 
No dose adjustment is required. 
Grade ≥ 3 non-
hematologic toxicity (if 
persisting despite 
medical treatment) 
Withhold until adverse event resolves to: 
x 
Grade ≤ 1 
x 
Grade ≤ 2 (if not considered a safety risk for the patient 
e.g. pneumonitis, ILD should cause discontinuation of 
palbociclib) 
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CTCAE Grade 
Dose Modification 
Resume at next lower dose. 
3.5 
Supportive Care  
3.5.1 
All supportive measures consistent with optimal patient care will be 
given throughout the study with the exception of growth factor 
support, which can be provided at the investigator’s discretion per 
ASCO guidelines. 
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: 
x 
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. 
x 
Patient withdraws consent. 
x 
Patient experiences unacceptable toxicity. 
x 
Non-protocol therapies are administered. 
x 
Disease progression 
3.7 
Duration of Follow-Up  
Refer to the MATCH Master Protocol for specifics on the duration of follow-up. 
 

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4. 
Study Parameters 
4.1 
Therapeutic Parameters for Palbociclib Treatment  
NOTE: 
In addition to the study parameters listed in the MATCH Master Protocol, the below parameters must also be 
performed for patients receiving palbociclib 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 
Cycle 1 & 2, 
Day 14 
Every 2 
Cycles 
H&P, Weight, Vital signsA 
X 
 XJ 
 
 
 
X 
Performance status 
X 
 XJ 
 
 
 
X 
CBC w/diff, pltsB 
X 
 XJ 
 XL 
 
 
X 
Serum chemistryB 
X 
 XJ 
 
 
 
X 
Radiologic evaluationD 
X 
 
 
 XD 
 
 XF 
E-HCGC 
X 
 
 
 
 
 
Toxicity AssessmentG 
 
X 
 
 
X 
 XF 
Pill Count/DiaryH 
 
X 
 
 
X 
 
ECGK 
X 
 XI 
 
 
 
 
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. 
D. Disease measurements are repeated every 2 cycles for the first 26 cycles, and every 3 cycles thereafter 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 myeloma patients, please refer to Section 6.4 of the MATCH Master Protocol for additional 

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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: 
x 
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. 
x 
Screening biopsies for additional aMOI assessments after registration to appropriate screening step, if applicable (Step 2 or Step 4). 
x 
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 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 required every subsequent 
cycle. 
I. 
As clinically indicated. 
J. 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.  
K. Within 8 weeks of treatment assignment. 
L. Mid-cycle blood tests are only required for Cycle 1 and Cycle 2. 
 
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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. 
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5.1 
Palbociclib (PD-0332991) (NSC 772256) 
5.1.1 
Other Names  
PD 0332991-00 (free base), PD 0332991-0054 (isethionate salt), 
Ibrance 
5.1.2 
Classification  
Cyclin-dependent kinase (CDK) inhibitor 
5.1.3 
Mode of Action  
Palbociclib is a highly selective and reversible oral inhibitor of cyclin-
dependent kinases 4 and 6. Inhibition of Cdk 4/6 results in cell cycle 
arrest from G1 to S phase. 
5.1.4 
Storage and Stability  
Storage:  Store at 20-25°C (68-77°F); excursions permitted between 
15-30° C (59-86° F). 
Stability: 
Refer to the package label for expiration. 
5.1.5 
Dose Specifics  
Palbociclib 125 mg, by mouth once daily for 21 days with 7 days off 
5.1.6 
Preparation  
Palbociclib capsules are supplied by Pfizer, Inc. and distributed by the 
Pharmaceutical Management Branch, CTEP/DCTD/NCI as 
commercially labeled 21-count bottles in the following strengths: 
x 
75 mg hard gelatin capsule (size 2) with light orange cap and 
body, printed with white ink “Pfizer” on the cap and “PBC 75” on 
the body. 
x 
100 mg hard gelatin capsule (size 1) with caramel cap and light 
orange body, printed with white ink “Pfizer” on the cap and “PBC 
100” on the body. 
x 
125 mg hard gelatin capsule (size 0) with caramel cap and body, 
printed with white ink “Pfizer” on the cap and “PBC 125” on the 
body. 
Capsule excipients include microcrystalline cellulose, lactose 
monohydrate, sodium starch glycolate, colloidal silicon dioxide, and 
magnesium stearate. Gelatin capsule colorants include red iron oxide, 
yellow iron oxide, and titanium dioxide. White printing ink contains 
shellac, titanium dioxide, ammonium hydroxide, propylene glycol and 
simethicone. 
5.1.7 
Route of Administration  
Oral. Take by mouth once daily with a meal. 
5.1.8 
Incompatibilities  
In vitro data suggest that palbociclib is primarily metabolized by CYP 
3A4. Avoid any concomitant CYP 3A4 strong inhibitors or inducers 
during palbociclib administration. In vivo studies demonstrate that 
palbociclib is a weak inhibitor of CYP3A4; thus any sensitive 

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substrates of CYP 3A4 should be used with caution on study 
especially substrates with a narrow therapeutic index. 
Palbociclib is a weak inhibitor of P-glycoprotein (P-gp) and breast 
cancer resistance protein (BCRP) drug efflux transporters. The 
potential for interaction is considered low at clinically-relevant doses 
of palbociclib. 
5.1.9 
Side Effects  
See Section 3.3 for side effects. 
5.1.10 
Nursing/Patient Implications 
Women of child bearing potential (WOCBP) and men should use 
effective methods of contraception from the time of signing the 
informed consent though 16 weeks after the last dose of study agent, 
or agree to completely abstain from heterosexual intercourse. Also, 
women should not breastfeed until at least 3 weeks after completing 
treatment with the study agent. 
 

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6. 
Translational Studies 
Please refer to the MATCH Master Protocol for information on the Translational Studies.  
7. 
References 
1. 
Fry DW, Harvey PJ, Keller PR, et al. Specific inhibition of cyclin-dependent kinase 
4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. 
Molecular cancer therapeutics. 2004;3:1427-38. 
2. 
Schwartz GK, LoRusso PM, Dickson MA, et al. Phase I study of PD 0332991, a 
cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1). Br 
J Cancer. 2011;104:1862-8. 
3. 
Flaherty KT, Lorusso PM, Demichele A, et al. Phase I, dose-escalation trial of the 
oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-
day schedule in patients with advanced cancer. Clinical cancer research : an 
official journal of the American Association for Cancer Research. 2012;18:568-76. 
4. 
Dickson MA, Tap WD, Keohan ML, et al. Phase II trial of the CDK4 inhibitor 
PD0332991 in patients with advanced CDK4-amplified well-differentiated or 
dedifferentiated liposarcoma. Journal of clinical oncology : official journal of the 
American Society of Clinical Oncology. 2013;31:2024-8. 
5. 
DeMichele A, Clark AS, Tan KS, et al. CDK 4/6 inhibitor palbociclib (PD0332991) 
in Rb+ advanced breast cancer: phase II activity, safety, and predictive biomarker 
assessment. Clinical cancer research : an official journal of the American 
Association for Cancer Research. 2015;21:995-1001. 
6. 
Leonard JP, LaCasce AS, Smith MR, et al. Selective CDK4/6 inhibition with tumor 
responses by PD0332991 in patients with mantle cell lymphoma. Blood. 
2012;119:4597-607. 
7. 
Finn RS, Crown JP, Lang I, et al. The cyclin-dependent kinase 4/6 inhibitor 
palbociclib in combination with letrozole versus letrozole alone as first-line 
treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer 
(PALOMA-1/TRIO-18): a randomised phase 2 study. The Lancet Oncology. 
2015;16:25-35. 
8. 
Turner NC, Huang Bartlett C, Cristofanilli M. Palbociclib in Hormone-Receptor-
Positive Advanced Breast Cancer. The New England journal of medicine. 
2015;373:1672-3. 
9. 
Tsai JW, Li CF, Kao YC, et al. Recurrent amplification at 7q21.2 Targets CDK6 
gene in primary myxofibrosarcomas and identifies CDK6 overexpression as an 
independent adverse prognosticator. Annals of surgical oncology. 2012;19:2716-
25. 
10. 
Li M, Lockwood W, Zielenska M, et al. Multiple CDK/CYCLIND genes are amplified 
in medulloblastoma and supratentorial primitive neuroectodermal brain tumor. 
Cancer genetics. 2012;205:220-31. 
11. 
Mendrzyk F, Radlwimmer B, Joos S, et al. Genomic and protein expression 
profiling identifies CDK6 as novel independent prognostic marker in 
medulloblastoma. Journal of clinical oncology : official journal of the American 
Society of Clinical Oncology. 2005;23:8853-62. 
12. 
Gao J, Aksoy BA, Dogrusoz U, et al. Integrative analysis of complex cancer 
genomics and clinical profiles using the cBioPortal. Science signaling. 2013;6:pl1. 

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13. 
cBioPortal. 2015  [cited October 4, 2015]; Available from: http://www.cbioportal.org/ 
14. 
Zhang YX, Sicinska E, Czaplinski JT, et al. Antiproliferative effects of CDK4/6 
inhibition in CDK4-amplified human liposarcoma in vitro and in vivo. Molecular 
cancer therapeutics. 2014;13:2184-93. 
15. 
Ismail A, Bandla S, Reveiller M, et al. Early G(1) cyclin-dependent kinases as 
prognostic markers and potential therapeutic targets in esophageal 
adenocarcinoma. Clinical cancer research : an official journal of the American 
Association for Cancer Research. 2011;17:4513-22. 
16. 
Lu H, Schulze-Gahmen U. Toward understanding the structural basis of cyclin-
dependent kinase 6 specific inhibition. Journal of medicinal chemistry. 
2006;49:3826-31. 
17. 
Baughn LB, Di Liberto M, Wu K, et al. A novel orally active small molecule potently 
induces G1 arrest in primary myeloma cells and prevents tumor growth by specific 
inhibition of cyclin-dependent kinase 4/6. Cancer research. 2006;66:7661-7. 
18. 
Barton KL, Misuraca K, Cordero F, et al. PD-0332991, a CDK4/6 inhibitor, 
significantly prolongs survival in a genetically engineered mouse model of 
brainstem glioma. PLoS One. 2013;8:e77639. 
19. 
Olanich ME, Sun W, Hewitt SM, et al. CDK4 Amplification Reduces Sensitivity to 
CDK4/6 Inhibition in Fusion-Positive Rhabdomyosarcoma. Clinical cancer research 
: an official journal of the American Association for Cancer Research. 
2015;21:4947-59. 
20. 
Tang LH, Contractor T, Clausen R, et al. Attenuation of the retinoblastoma 
pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6. Clinical 
cancer research : an official journal of the American Association for Cancer 
Research. 2012;18:4612-20. 
21. 
Cen L, Carlson BL, Schroeder MA, et al. p16-Cdk4-Rb axis controls sensitivity to a 
cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells. 
Neuro Oncol. 2012;14:870-81. 
22. 
Dickson MA, Tap WD, Antonescu CR, et al. Final results of sequential phase 2 
studies of palbociclib (PD0332991) in CDK4-amplified liposarcoma.  2013 
European Cancer Congress; 2013; Amsterdam, Netherlands: European Journal of 
Cancer; 2013. p. S884. 
 
 
 
 

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Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1C: Palbociclib/CDK4, 6 
Appendix I 
 
Patient Pill Calendar 
 
Pill Calendar Directions 
1. Take your scheduled dose of each capsule.  
2. The capsules should be taken with food once daily for 21 days, and then take no 
study medicine for 7 days (rest days). Each cycle is 28 days long. 
3. Palbociclib capsules must be swallowed whole. 
4. If you forget, the missed capsules will not be taken later. 
5. If you vomit after taking your scheduled dose, it will not be made up or re-taken. You 
will continue to receive the next scheduled doses as prescribed. 
6. Please bring the empty bottle or any leftover capsules and your pill calendar to your 
next clinic visit. 
7. Store palbociclib capsules at room temperature. 
 
 

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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. 
Palbociclib 
DAY  
Date 
Time 
capsules 
taken 
Number of 
capsules 
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 
 
 
 
 
 
 
Days 22-28 are rest days – Do not take any capsules. 
 
Patient Signature: __________________________________ Date: _____________

ECOG-ACRIN 
EAY131-Z1C 
Cancer Research Group 
Version Date: August 19, 2020 
28 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1C: Palbociclib/CDK4, 6 
Appendix II 
 
Actionable Mutations for Sub-Protocol EAY131-Z1C 
 
Gene Name 
Variant 
ID 
Variant 
Type 
Level of Evidence 
Code 
Variant 
Description 
Rb IHC1 
CDK4 
CDK4 
CNV 
2 
Amplification 
Positiv
e 
CDK6 
CDK6 
CNV 
2 
Amplification 
Positiv
e 
1. Rb IHC will be done on archived specimens; those patients that are + on IHC for archived 
tumor specimens will be counted in the primary analysis. It is estimated, based on MATCH 
screening results to date, that at least 90% of patients will have Rb expression in their 
tumor. 
 
Rev. Add13 

ECOG-ACRIN 
EAY131-Z1C 
Cancer Research Group 
Version Date: August 19, 2020 
29 
Molecular Analysis for Therapy Choice (MATCH) 
MATCH Treatment Subprotocol Z1C: Palbociclib/CDK4, 6 
Appendix III 
 
PATIENT CLINICAL TRIAL WALLET CARD 
 
CLINICAL TRIAL WALLET CARD 
Show this card to all of your 
healthcare providers and keep 
it with you in case you go to 
the emergency room. 
Patient Name:        
Diagnosis:        
Study Doctor:       
Study Doctor Phone #:       
NCI Trial #:        
Study Drug(S):        
 
 
 
 
For more information: 1-800-4-CANCER 
cancer.gov | clinicaltrials.gov 
 
Rev. Add25