Clinical trial NCT04173507
Conditions: Advanced Lung Non-Squamous Non-Small Cell Carcinoma Recurrent Lung Non-Squamous Non-Small Cell Carcinoma Stage IV Lung Cancer AJCC v8 Stage IVA Lung Cancer AJCC v8 Stage IVB Lung Cancer AJCC v8
Sponsor: SWOG Cancer Research Network
Start date: 2020-02-14; Completion date: 2024-05-01
Enrollment: 47 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
This phase II LUNG-MAP treatment trial studies how well combination treatment (talazoparib plus avelumab) works in treating patients with non-squamous non-small cell lung cancer that has an STK11 gene mutation and has come back (recurrent) or is stage IV. Talazoparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as avelumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Immunotherapy drugs given as single therapies or in combination with chemotherapy do not appear to work as well in lung cancer cells with mutations in the STK11 gene versus those that do not have the mutation. Adding the medicine talazoparib to the immunotherapy drug avelumab may work better in treating lung cancers that have an STK11 gene mutation.

Detailed description:
PRIMARY OBJECTIVES:

I. To evaluate the objective response rate (ORR) (confirmed and unconfirmed, complete and partial) with talazoparib plus avelumab in patients with stage IV or recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 genomic alterations that were previously-treated with anti-PD-1/PD-L1 therapy and platinum-based chemotherapy.

II. To evaluate disease control rate at 12 weeks (DCR12) after registration.

SECONDARY OBJECTIVES:

I. To evaluate investigator assessed progression-free survival (IA-PFS). II. To evaluate overall survival (OS). III. To evaluate duration of response (DOR) among responders. IV. To evaluate the frequency and severity of toxicities.

TRANSLATIONAL MEDICINE OBJECTIVES:

I. To collect, process, and bank cell-free deoxyribonucleic acid (DNA) (cfDNA) at baseline, cycle 3 day 1, progression, and end of treatment for future development of a proposal to evaluate comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and examine molecular mechanisms of resistance to talazoparib and avelumab.

II. To establish a tissue/blood repository from patients with refractory non-small cell lung cancer (NSCLC).

III. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent somatic mutations in KEAP1 detected on the Foundation Medicine Inc. (FMI) panel from the LUNGMAP screening protocol.

IV. To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent mutations in ATM or other DNA damage response genes detected on the FMI panel from the LUNGMAP screening protocol.

V. To evaluate the association between tumor mutational burden (TMB) measured on the FMI panel from the LUNGMAP screening protocol and clinical outcomes (ORR, IA-PFS, OS).

OUTLINE:

Patients receive talazoparib orally (PO) daily and avelumab intravenously (IV) over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up until death or 3 years after sub-study registration.

Arms: arm 1: Patients receive talazoparib PO daily and avelumab IV over 60 minutes on days 1 and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions: intervention 1: Avelumab intervention 2: Talazoparib intervention 3: Talazoparib Tosylate
Intervention descriptions: intervention 1: Given IV intervention 2: Given PO intervention 3: Given PO

Protocol documents:
Prot_SAP_000.pdf: 
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PRIVILEGED COMMUNICATION 
FOR INVESTIGATIONAL USE ONLY 
 
S1900C: Talazoparib + Avelumab – STK11 
 
SWOG CANCER RESEARCH NETWORK 
TITLE 
LUNGMAP, A MASTER PROTOCOL TO EVALUATE BIOMARKER-DRIVEN THERAPIES AND 
IMMUNOTHERAPIES IN PREVIOUSLY-TREATED NON-SMALL CELL LUNG CANCER (LUNG-MAP 
SCREENING STUDY) 
 
S1900C, A PHASE II STUDY OF TALAZOPARIB PLUS AVELUMAB IN PATIENTS WITH STAGE IV 
OR RECURRENT NON-SQUAMOUS NON-SMALL CELL LUNG CANCER BEARING PATHOGENIC 
STK11 GENOMIC ALTERATIONS (LUNG-MAP SUB-STUDY) 
 
NCT#04173507 
 
This is an FDA Registration Trial. Additional site requirements include: 
• 
maintenance of a Trial Master File (https://www.swog.org/sites/default/files/docs/2017-
10/Guidance%20on%20FDA%20Inspection.pdf )   
• 
completion of a protocol specific Delegation of Task Log (DTL) (see Section 13.2) 
• 
additional monitoring (see LUNGMAP Appendix 18.2) 
 
LUNGMAP and its sub-studies are being conducted under SWOG IND 143217 and CIRB. The 
LUNGMAP study is considered a single study under one IND, consisting of the screening protocol 
and multiple sub-studies. Each sub-study protocol operates independently and has its own 
version date. For CIRB Continuing Reviews, LUNGMAP and its sub-studies will be processed 
separately but have the same expiration date as the LUNGMAP screening protocol.  
 
 
 
SUB-STUDY CHAIRS: 
 
Ferdinandos Skoulidis, M.D., Ph.D., MRCP  
NCTN Group:  SWOG 
UT/MD Anderson Cancer Center  
1400 Holcombe Boulevard 
Houston, Texas 77030 
Phone: 713/792-6363 
Fax: 713/792-1221 
E-mail: FSkoulidis@mdanderson.org   
 
Jennifer Marie Suga, M.D., MPH 
NCTN Group: SWOG 
Kaiser Permanente Cancer Research Center  
975 Sereno Drive 
Vallejo, CA 94589  
Phone: 707/651-1077 
Fax: 707-651-2798 
E-mail:  Jennifer.M.Suga@kp.org  
 
 
STUDY AGENTS: 
 
NCI Supplied Investigational Agents:  
Talazoparib (PF-06944076) (NSC 771561) 
Avelumab (NSC 799232) 
 
BIOSTATISTICIANS: 
 
Mary Redman, Ph.D. 
Katherine Minichiello, M.S. 
SWOG Statistic & Data Management Center 
1100 Fairview Ave N, M3-C102 
Seattle, WA 98109-1024 
Phone: 206/667-4623 
FAX: 206/667-4408 
E-mail: mredman@fredhutch.org   
E-mail: kmini@fredhutch.org  
   
 
 
 
 
 


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PARTICIPANTS 
 
 
 
 
 
 
 
 
 
U.S.-Only Participants: 
 
ALLIANCE/Alliance for Clinical Trials in Oncology 
ECOG-ACRIN/ECOG-ACRIN Cancer Research Group 
NRG/NRG Oncology 
SWOG/SWOG Cancer Research Network 


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TABLE OF CONTENTS 
 
 
TITLE ………………………………………………………………………………………………………………..1 
TABLE OF CONTENTS ............................................................................................................................... 3 
PROTOCOL CONTACT INFORMATION ..................................................................................................... 5 
CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION ....................... 6 
SCHEMA ....................................................................................................................................................... 7 
1.0 
OBJECTIVES .................................................................................................................................. 8 
1.1 
Primary Objectives ........................................................................................................................... 8 
1.2 
Secondary Objectives ...................................................................................................................... 8 
1.3 
Translational Medicine Objectives ................................................................................................... 8 
2.0 
BACKGROUND ............................................................................................................................... 8 
2.1 
Rationale for Biomarker and Drug Selection.................................................................................... 8 
2.2 
Rationale for Inclusion in Lung-MAP .............................................................................................. 11 
2.3 
Study Design .................................................................................................................................. 12 
2.4 
Rationale ........................................................................................................................................ 12 
2.5 
Data ................................................................................................................................................ 12 
2.6 
Inclusion of Women and Minorities and Planned Enrollment Report ............................................ 13 
3.0 
DRUG INFORMATION .................................................................................................................. 14 
3.1 
Talazoparib (PF-06944076) (NSC 771561) (IND143217) ............................................................. 14 
3.2 
Avelumab (MSB0010718C; Bavencio®) (NSC 799232) (IND 143217) ......................................... 19 
3.3 
NCI-Supplied Agent Ordering and Agent Accountability ............................................................... 24 
4.0 
STAGING CRITERIA ..................................................................................................................... 25 
5.0 
ELIGIBILITY CRITERIA ................................................................................................................ 27 
5.1 
Disease Related Criteria ................................................................................................................ 27 
5.2 
Prior/Concurrent Therapy Criteria .................................................................................................. 28 
5.3 
Clinical/Laboratory Criteria ............................................................................................................. 29 
5.4 
Specimen Submission Criteria ....................................................................................................... 31 
5.5 
Regulatory Criteria ......................................................................................................................... 31 
6.0 
STRATIFICATION FACTORS ....................................................................................................... 32 
7.0 
TREATMENT PLAN ...................................................................................................................... 32 
7.1 
Precautions .................................................................................................................................... 32 
7.2  
Pre-Medication and Supportive Care ............................................................................................. 32 
7.3 
Disease Assessment ...................................................................................................................... 32 
7.4 
Treatment – S1900C ...................................................................................................................... 33 
7.5 
Drug Compliance Documentation .................................................................................................. 34 
7.6  
Criteria for Removal from Protocol Treatment ............................................................................... 34 
7.7  
Discontinuation of Treatment ......................................................................................................... 34 
7.8 
Follow-Up Period ............................................................................................................................ 34 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS .............................................. 34 
8.1 
NCI Common Terminology Criteria for Adverse Events ................................................................ 34 
8.2 
General Considerations ................................................................................................................. 35 
8.3 
Dose Interruptions – Avelumab ...................................................................................................... 35 
8.4 
Dose Modifications – Talazoparib .................................................................................................. 43 
8.5 
Dose Modification Contacts ........................................................................................................... 46 
8.6 
Adverse Event Reporting Requirements........................................................................................ 46 
8.7 
Serious Adverse Event Reporting Requirements .......................................................................... 47 
9.0 
STUDY CALENDAR ...................................................................................................................... 52 
9.1 
Talazoparib and Avelumab ............................................................................................................ 52 
10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS ..................................................... 55 
10.1 
Measurability of Lesions................................................................................................................. 55 
10.2 
Objective Status at Each Disease Evaluation ................................................................................ 56 
10.3 
Best Response ............................................................................................................................... 58 
10.4 
Performance Status ....................................................................................................................... 58 
10.5 
Time to Death ................................................................................................................................. 59 
10.6 
Investigator-Assessed Progression-Free Survival ......................................................................... 59 
10.7 
Progression-Free Survival by Central Review ............................................................................... 59 


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10.8 
Duration of Response (DoR) .......................................................................................................... 59 
10.9 
Disease Control Rate at 12 Weeks (DCR12) ................................................................................ 59 
11.0 
STATISTICAL CONSIDERATIONS .............................................................................................. 60 
11.1 
Sample Size with Power Justification ............................................................................................ 60 
12.0 
DISCIPLINE REVIEW .................................................................................................................... 62 
12.1 
Radiology Review .......................................................................................................................... 62 
13.0 
REGISTRATION GUIDELINES ..................................................................................................... 62 
13.1 
Registration Timing ........................................................................................................................ 62 
13.2  
Investigator/Site Registration ......................................................................................................... 63 
14.0 
DATA SUBMISSION SCHEDULE ................................................................................................ 63 
14.1 
Data Submission Requirement ...................................................................................................... 63 
14.2 
Master Forms ................................................................................................................................. 63 
14.3 
Data Submission Procedures ........................................................................................................ 63 
14.4 
Data Submission Overview and Timepoints .................................................................................. 65 
15.0 
SPECIAL INSTRUCTIONS............................................................................................................ 67 
15.1 
Specimen Flow Diagram ................................................................................................................ 67 
15.2 
SWOG Specimen Tracking System (STS) .................................................................................... 67 
15.3  
LUNGMAP ctDNA Assay – Peripheral Whole Blood (REQUIRED FOR PATIENTS) ................... 67 
15.4 
Translational Medicine and Banking (OPTIONAL FOR PATIENT) ............................................... 69 
15.5 
Radiology Review (REQUIRED) .................................................................................................... 71 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS ................................................................... 72 
17.0 
BIBLIOGRAPHY ............................................................................................................................ 74 
18.0 
APPENDIX ..................................................................................................................................... 77 
18.1 
New York Heart Association Classification .................................................................................... 78 
18.2 
Monitoring Plan .............................................................................................................................. 79 
18.3 
Instructions for the SWOG Biospecimen Bank .............................................................................. 80 
18.4  
Patient Diary – Talazoparib     SWOG Study: S1900C ................................................................. 81 
18.5 
PATIENT DRUG INFORMATION HANDOUT AND WALLET CARD ............................................ 84 
18.6  
Site Temperature Excursion Report Form ..................................................................................... 86 
 


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PROTOCOL CONTACT INFORMATION  
 
Patient Advocate: 
Judy Johnson, MBA 
E-mail: judyjohnson.519@gmail.com 
Phone: 314/477-6139 
 
Eligibility, RAVE, Data Submission: 
 
SWOG Statistics and Data Management Center  
E-mail: LUNGMAPquestion@crab.org 
Phone: 206/652-2267 
 
Regulatory, Protocol, Informed Consent: 
 
SWOG Operations Office  
E-mail: protocols@swog.org 
Phone: 210/614-8808 
 
Medical Queries (treatment or toxicity related 
questions): 
 
E-mail: S1900CMedicalQuery@swog.org 
 
Investigational Drug questions: 
Requests for Investigator’s Brochures: 
 
See Protocol Section 3.0 
 
Temperature Excursion Reports: 
 
GCSTempExcursionSupport@pfizer.com  
 
Specimen Tracking System (STS) Amendments, 
Errors, Connectivity Issues and Technical issues 
with the SWOG CRA Workbench: 
 
technicalquestion@crab.org  
 
Foundation Medicine, Inc. (for ordering ctDNA 
blood collection kits only): 
 
FMI Client Services  
E-mail: lung.map@FoundationMedicine.com 
Phone: 1-888/988-3639 
 
Cancer Therapy and Evaluation Program – 
Identity and Access Management (CTEP-IAM): 
 
To review CTEP-IAM account (new requests, 
reset passwords): 
https://ctepcore.nci.nih.gov/iam/index.jsp 
 
Access to iMedidata Rave or Delegation of Task 
Log (DTL): 
 
See Protocol Section 14.3 or contact  
CTSU Help Desk:  
Phone: 1-888-823-5923 or Email: 
ctsucontact@westat.com 
 
Questions related to 
Oncology Patient Enrollment Network (OPEN): 
 
See LUNGMAP Protocol Section 13.2 or contact  
CTSU Help Desk:  
Phone: 1-888-823-5923 or Email: 
ctsucontact@westat.com 
 
Patient Transfers: 
 
patienttransfer@crab.org 
 
TRIAD installations: 
 
https://triadinstall.acr.org/triadclient/   
Questions: TRIAD-Support@acr.org  
 
Adverse Event Reporting questions: 
 
See Section 8.6 
E-mail: adr@swog.org 
 
 
 


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CANCER TRIALS SUPPORT UNIT (CTSU) ADDRESS AND CONTACT INFORMATION 
CONTACT INFORMATION 
For regulatory requirements: 
For patient enrollments: 
For data submission: 
Regulatory documentation must 
be submitted to the CTSU via 
the Regulatory Submission 
Portal 
 
(Sign in at www.ctsu.org, and 
select the Regulatory > 
Regulatory Submission.) 
 
Institutions with patients waiting 
that are unable to use the Portal 
should alert the CTSU 
Regulatory Office immediately 
at 1-866-651-2878 to receive 
further instruction and support.   
 
Contact the CTSU Regulatory 
Help Desk at 1-866-651-2878 
for regulatory assistance. 
 
Refer to the patient enrollment 
section of the protocol for 
instructions on using the 
Oncology Patient Enrollment 
Network (OPEN). OPEN is 
accessed at 
https://www.ctsu.org/OPEN_SYS
TEM/or https://OPEN.ctsu.org. 
 
Contact the CTSU Help Desk with 
any OPEN-related questions by 
phone or email : 1-888-823-5923, 
or ctsucontact@westat.com.  
Data collection for this study will 
be done exclusively through 
Medidata Rave.  Refer to the 
data submission section of the 
protocol for further instructions.  
 
 
The most current version of the study protocol and all supporting documents must be downloaded 
from the protocol-specific page located on the CTSU members’ website(https://www.ctsu.org).  Access 
to the CTSU members’ website is managed through the Cancer Therapy and Evaluation Program - 
Identity and Access Management (CTEP-IAM) registration system and requires log in with a CTEP-IAM 
username and password.  
 
For patient eligibility or data submission questions contact the SWOG Statistics and Data 
Management Center (SDMC) by phone or email: 
 
206/652-2267 
LUNGMAPQuestion@crab.org  
 
For treatment or toxicity related questions contact S1900CMedicalQuery@swog.org. 
For non-clinical questions (i.e. unrelated to patient eligibility, treatment, or clinical data 
submission)  
Contact the CTSU Help Desk by phone or e-mail:  
CTSU General Information Line – 1-888-823-5923, or ctsucontact@westat.com.  All calls and 
correspondence will be triaged to the appropriate CTSU representative.  
 
 
 
 


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SCHEMA 
 
 
LUNGMAP Registration a  
 
 
 
Common Broad Platform CLIA Biomarker Profiling b 
 
 
Non-Squamous  
with pathogenic STK11 genomic alterations c  
 
 
 
S1900C Registration 
 
 
 
Talazoparib plus Avelumab 
 
 
 
Off Protocol Treatment Reasons Met d 
 
 
 
 
a. 
See LUNGMAP Section 5.1 for registration information.  
 
b. 
Notification of sub-study assignment will be provided by the SWOG Statistics and Data 
Management Center (SDMC) (see LUNGMAP Section 11.0 for details). 
 
c. 
See S1900C Section 5.1 for the definition of eligible STK11 genomic alterations by Foundation 
Medicine Inc. criteria. 
 
d. 
Upon progression (as defined in Section 10.2), patients may be eligible for another sub-study. The 
new sub-study assignment will be determined by the SWOG SDMC (see Section 14.4). 
 
 


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1.0 
OBJECTIVES 
 
1.1 
Primary Objectives  
 
a. 
To evaluate the objective response rate (ORR) (confirmed and unconfirmed, 
complete and partial) with talazoparib plus avelumab in patients with Stage IV or 
recurrent non-squamous non-small cell lung cancer bearing pathogenic STK11 
genomic alterations that were previously-treated with anti-PD-1/PD-L1 therapy and 
platinum-based chemotherapy. 
 
b. 
To evaluate disease control rate at 12 weeks (DCR12) after registration. 
 
1.2 
Secondary Objectives 
 
a. 
To evaluate investigator assessed progression-free survival (IA-PFS). 
 
b. 
To evaluate overall survival (OS). 
 
c. 
To evaluate duration of response (DOR) among responders. 
 
d. 
To evaluate the frequency and severity of toxicities. 
 
1.3 
Translational Medicine Objectives 
 
a. 
To collect, process, and bank cell-free DNA (cfDNA) at baseline, Cycle 3 Day 1, 
progression, and end of treatment for future development of a proposal to evaluate 
comprehensive next-generation sequencing of circulating tumor DNA (ctDNA) and 
examine molecular mechanisms of resistance to talazoparib and avelumab. 
 
Note: The translational medicine proposal to use these specimens will be 
submitted as a revision to CTEP for approval, prior to SDMC review of assay 
results. 
b. 
To establish a tissue/blood repository from patients with refractory non-small cell 
lung cancer (NSCLC). 
 
c. 
To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent 
somatic mutations in KEAP1 detected on the Foundation Medicine Inc. (FMI) panel 
from the LUNGMAP screening protocol. 
 
d. 
To evaluate clinical outcomes (ORR, IA-PFS, OS) in patients with concurrent 
mutations in ATM or other DNA damage response genes detected on the FMI 
panel from the LUNGMAP screening protocol. 
 
e. 
To evaluate the association between tumor mutational burden (TMB) measured 
on the FMI panel from the LUNGMAP screening protocol and clinical outcomes 
(ORR, IA-PFS, OS). 
 
 
 
 
 
2.0 
BACKGROUND 
 
2.1 
Rationale for Biomarker and Drug Selection 
 
Inactivating genomic alterations in the STK11 tumor suppressor gene represent one of the 
most common somatic genetic events in non-small cell lung cancer (NSCLC) (17% of all 


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lung adenocarcinomas-LUAC) and frequently co-occur with mutant KRAS (~25% of all 
KRAS-mutant NSCLC harbor STK11 co-mutations). (1,2) STK11 encodes LKB1, a serine 
threonine kinase with an established role in the regulation of cellular growth, metabolism 
and polarity through phosphorylation of AMP-activated protein kinase (AMPK) and 14 
AMPK-related kinases (ARKs). (3) STK11 somatic mutations are typically spread across 
the STK11 gene without major hotspots, and are, in their vast majority, inactivating. (4,5)  
 
Loss of function genomic alterations in STK11 (non-synonymous mutations or bi-allelic 
loss) have been previously identified as a major determinant of primary resistance to PD-
1/PD-L1 axis blockade in KRAS-mutant NSCLC and more broadly among non-squamous 
non-small cell lung cancer regardless of KRAS status. (6,7,8, 9) Loss of STK11 is 
associated with establishment of a “cold”, non-T-cell inflamed tumor immune 
microenvironment with low density of infiltrating CD8+ lymphocytes and low expression of 
PD-L1 on tumor cells. (10,11,12,13) Importantly, establishment of an inert tumor immune 
microenvironment in STK11-deficient NSCLC occurs despite the presence of intermediate 
or high tumor mutation burden. (14,15,16) It is also notable that the PD-1 inhibitor 
recalcitrant phenotype of STK11 somatic genomic alterations extends to PD-L1 positive 
(PD-L1 tumor proportion score ≥1%) non-squamous non-small cell lung cancer, and is 
therefore at least partially independent of PD-L1 status. (17) In immune-competent murine 
models of non-small cell lung cancer (syngeneic as well as genetically engineered murine 
models) loss of STK11 directly promotes PD-1 inhibitor resistance, supporting a causal 
effect. (18,19) Thus, STK11-deficient NSCLC represents a prevalent, molecularly-defined 
subgroup of NSCLC with de novo resistance to PD-1/PD-L1 inhibitor monotherapy, despite 
the presence of intermediate or high tumor mutation burden. More recently, STK11 
genomic alterations were also associated with worse clinical outcomes with 
pemetrexed/carboplatin (or cisplatin)/pembrolizumab. In addition, STK11-mutant patients 
harboring co-mutations in KEAP1 exhibited lower ORR and shorter PFS and OS with 
chemo-immunotherapy. These findings support focused clinical efforts to identify rational 
combination therapeutic strategies aimed at re-establishing effective anti-tumor immunity 
in STK11-deficient tumors. 
 
The rationale for combining PARP-inhibitors with PD-1/PD-L1 inhibitors 
There is compelling rationale for combining PARP inhibitors with PD-1/PD-L1 inhibitors in 
order to enhance anti-tumor immune responses. Recent work in small cell lung cancer 
demonstrated that treatment with the PARP inhibitor olaparib can significantly potentiate 
the anti-tumor effect of PD-L1 blockade and trigger dramatic and sustained tumor 
regressions in immune competent animal models of small cell lung cancer. (20) Critically, 
the impressive clinical activity of combination therapy occurred despite the lack of 
significant anti-tumor activity of each individual agent, suggesting that sensitization to anti-
PD-L1 therapy occurs as a result of the therapeutic combination. In agreement with this, 
combination therapy – but not each treatment alone - increased the densities of infiltrating 
CD3+ and CD8+ T lymphocytes. Notably, PARP inhibitor therapy resulted in increased 
tumor PD-L1 expression. (21) 
 
Mechanistically, exposure to olaparib activates the STING/TBK1/IRF3 innate immune 
pathway that responds to cytosolic DNA. (22, 23, 24) Engagement of innate immune 
signaling leads to increased tumor cell expression of PD-L1 and production of IFNβ that 
promotes a type I interferon response. Importantly, activation of innate immune signaling 
results in the production of increased levels of CCL5 and CXCL10, chemokines that 
mediate the recruitment and activation of cytotoxic T lymphocytes. (25) Thus, engagement 
of innate immune signaling pathways mediates the profound synergy between olaparib and 
anti-PD-L1 therapy. In addition to promoting activation of the STING/TBK1/IRF3 pathway, 
DNA damage can further promote increased antigen presentation and increased 
expression of natural killer cell ligands (for example NKG2D), thus providing additional, 


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non-mutually exclusive pathways through which PARP inhibition may synergize with PD-
1/PD-L1 blockade. (26)  
 
Pre-clinical evidence of PARP inhibitor activity in STK11-mutant NSCLC  
There is direct experimental evidence that STK11-deficient NSCLC cell lines are selectively 
sensitive to talazoparib and engage innate immune signaling following exposure to modest 
talazoparib concentrations. In order to assess the impact of STK11 status on sensitivity to 
talazoparib in NSCLC, four previously established STK11 proficient/deficient NSCLC pairs 
were utilized by re-introducing full-length functional STK11 or empty vector in the H460, 
H2030, A549 and H23 STK11-mutant NSCLC lines that do not express STK11 protein. 
(27,28) STK11-isogenic cell line pairs were then exposed to increasing concentrations of 
talazoparib in vitro for 72 hours. Strikingly, STK11-deficient derivatives of all four NSCLC 
lines (referred to as Control) were more sensitive to talazoparib compared with their STK11 
proficient counterparts (referred to as LKB1 OE) that were resistant to talazoparib (Figure 
1). These results suggest that in NSCLC cell lines, sensitivity to talazoparib is at least 
partially dependent on STK11 status. Critically, exposure of the four STK11-deficient 
NSCLC cell lines (A549, H460, H2030 and H23) to low concentrations of talazoparib 
(50nM-100nM) for 48 hours resulted in elevated levels of phospho-TBK1 Ser172 protein, 
indicating that PARP inhibition engages innate immune signaling in this context (Figure 2). 
Thus, there is direct experimental evidence that exposure to talazoparib can result in 
immune pathway activation in STK11-deficient NSCLC cell lines. These results suggest 
that STK11-mutant NSCLC may be particularly amenable to combination therapy with 
talazoparib and avelumab. These results are further supported by work from other groups 
that showed that STK11 deficiency is associated with sensitivity to different PARP inhibitors 
(29), as well as to genetic and pharmacological inhibition of CHK1 (30,31) and 
pharmacological inhibition of the WEE1 kinase. (32) In addition, it was recently reported 
that STK11 protein is recruited to sites of double-strand DNA breaks (marked by 
accumulation of ɣH2AX) upon genotoxic stress and plays a role in the regulation of BRCA1 
expression through a post-transcriptional mechanism. (33) Thus, it has been postulated 
that STK11 may exert a more direct role in the DNA damage response which may underpin 
the enhanced sensitivity of STK11-deficient NSCLC cell to PARP inhibitors.  
 
Taken together these findings constitute rationale for combination therapy with PARP 
inhibitors and checkpoint inhibitor blockade to overcome the intrinsic resistance of STK11-
mutant NSCLC to PD-1/PD-L1 inhibitor monotherapy.  
 


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Figure 1. Sensitivity of NSCLC cell lines to talazoparib is at least partially dependent on STK11 status. 
Dose response curves of four STK11 deficient /proficient isogenic non-small cell lung cancer cell line pairs to 
the PARP1 inhibitor talazoparib. Cell viability was measured after exposure to the indicated concentrations of 
talazoparib for 120 hours using the Cell Counting Kit-8 (Dojindo Molecular Technologies, Inc). Note that in 
each of the four isogenic pairs STK11 deficiency is associated with increased sensitivity to talazoparib, 
whereas re-introduction of full-length STK11 confers resistance.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.2 
Rationale for Inclusion in Lung-MAP 
The Lung-MAP study is a master protocol for genomic screening and multi-sub-study 
testing of drug/biomarker combinations in a Phase II/III setting compatible with subsequent 
FDA approval. Genomic screening of a large patient resource provided by sites 
participating in the NCI National Clinical Trials Network (NCTN) identifies a series of 
molecular targets/biomarkers which are matched to new drugs, leading to appropriate sub-
study assignment and drug treatment.  Each molecular target in Lung-MAP is represented 
by a biomarker for which there is an analytically validated diagnostic assay. This approach 
 
 
 
Figure 2. Engagement of innate immune signaling following exposure to talazoparib in STK11-mutant 
NSCLC cell lines. Immunoblotting for phospho-TBK1 (Ser172), a marker of innate immune pathway activation 
following exposure to the indicated concentrations of talazoparib for 72 hours in four naturally STK11-deficient 
non-small cell lung cancer cell lines. Cleaved PARP is a marker of apoptosis and GAPDH serves as loading 
control. Note that exposure to modest concentrations of talazoparib results in increased expression of 
phospho-TBK1 in all four STK11 deficient NSCLC cell lines. These results indicate that treatment with 
talazoparib results in activation of innate immune signaling in STK11-deficient NSCLC cell lines.                        


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provides the basis for this large-scale screening/clinical registration trial with the ability to 
screen patients, either through genomic analysis or immunohistochemistry-based assays, 
with homogeneous eligibility criteria and direct them to a sub-study based on the results of 
screening diagnostic tests.  
 
Based on the results of the tumor analysis, patients will either be assigned to one of the 
biomarker-driven sub-studies or to a ‘non-match’ sub-study for patients with none of the 
eligibility biomarkers. The biomarker-driven sub-studies are designed around a 
genotypically-defined alteration in the tumor and a drug that targets it. The non-match 
studies are designed around an investigational agent with the potential for efficacy in a 
broader population. For a full description and justification of the study design, refer to the 
LUNGMAP Screening Protocol. 
 
Prevalence of STK11 somatic mutations and bi-allelic loss in non-squamous non-small cell 
lung cancer: 
Based on data from the TCGA as well as the Foundation Medicine database, the frequency 
of pathogenic somatic mutations and bi-allelic deletions in STK11 is ~17% of non-
squamous NSCLC. In view of the low prevalence of STK11 genomic alterations in pure 
squamous cell lung cancer and the lack of preliminary data regarding the  impact of STK11 
genomic alterations on clinical outcomes with PD-1 axis blockade in this histological 
subtype, patients with pure squamous non-small cell lung cancer will not be included in 
this study. 
 
2.3 
Study Design 
 
This is a single arm, open label signal seeking study assessing the efficacy of talazoparib 
plus avelumab in patients with non-squamous NSCLC with pathogenic STK11 genomic 
alterations (mutations or bi-allelic deletion using the FoundationOne assay), whose 
disease has progressed following initiation of platinum-doublet chemotherapy and anti-PD-
1 or anti-PD-L1 therapy, administered concurrently or sequentially. The co-primary 
objectives are to evaluate the response rate and disease control rate at 12 weeks for 
talazoparib and avelumab among patients found to have pathogenic STK11 genomic 
alterations on tumor genomic profiling using the FoundationOne assay.  
  
2.4 
Rationale 
 
Inactivating STK11 genomic alterations are prevalent in non-squamous NSCLC (~17%) 
and constitute a major driver of primary resistance to PD-1 axis blockade, irrespective of 
tumor cell PD-L1 expression and tumor mutational burden. Given the high prevalence of 
STK11 alterations in non-squamous NSCLC, identification of rational therapeutic 
approaches to restore effective anti-tumor immunity in this molecular subset constitutes a 
major unmet clinical need. Combination of talazoparib, a potent catalytic PARP inhibitor 
with additional PARP trapping activity with avelumab, a fully human PD-L1 inhibitory 
antibody, represents a rational therapeutic strategy for this immunotherapy resistant 
subgroup of NSCLC. If successful, this approach has the potential to result in meaningful 
prolongation of overall survival and improved quality of life for non-squamous NSCLC 
patients bearing STK11 mutant tumors.  
  
2.5 
Data 
 
Avelumab (10mg/kgr IV every 2 weeks) was compared with docetaxel for patients with 
Stage IIIB, IV or recurrent NSCLC and disease progression after treatment with a platinum-
containing doublet in the randomized open label JAVELIN Lung 200 Phase 3 clinical trial. 
(34) Among 529 PD-L1 positive patients (≥1% cutoff) the ORR with avelumab was 19% 
compared to 12% in the docetaxel group (OR 1.76, 95% CI 1.08-2.86; P=0.011). Overall 


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survival did not differ significantly between the two groups (mOS 11.4 months [95% CI 9.4-
13.9] vs 10.3 months [8.5-13.0]; HR 0.90 [96% CI 0.72-1.12]; one sided P=0.16). Avelumab 
was overall well tolerated with grade 3-5 adverse events observed in 10% of avelumab-
treated patients. In the avelumab group, the most common treatment-related adverse 
events (All grade) were infusion-related reactions (17%) and decreased appetite (9%) and 
the most common grade 3 or worse treatment-related adverse events were infusion-related 
reaction (2%) and increased lipase (1%).  
 
Talazoparib was evaluated in the first-in-human multicenter Phase I study NCT01286897 
consisting of a dose-escalation (Part 1) cohort in patients with solid tumors and a dose 
expansion (Part 2) cohort in patients with tumors predicted to be potentially sensitive to 
PARP inhibition, including patients with germline pathogenic BRCA1/2 mutations; triple-
negative breast cancer; high grade serous papillary and/or undifferentiated  ovarian, 
fallopian tube or peritoneal  cancers; castration-resistant prostate and pancreatic cancers, 
Ewing’s sarcoma and small cell lung cancer. (35) The MTD and RP2D was determined to 
be 1 mg/day, with an elimination half-life of 50 hours. The most common G3/G4 treatment-
related adverse events were anemia (24%), thrombocytopenia (18%) and neutropenia 
(10%). Among 23 patients with small cell lung cancer enrolled in the dose expansion cohort 
and treated with 1 mg/day of talazoparib the ORR was 9% and the clinical benefit rate 
(defined as PR/CR + SD lasting ≥16 weeks) was 26%.  
 
The combination of avelumab plus talazoparib is being evaluated in the open-label phase 
1b/2 JAVELIN PARP Medley (B9991025, NCT03330405) clinical trial in ~316 PD-1/PD-L1 
inhibitor- naïve patients with selected solid tumors, including patients with NSCLC. 
Different daily doses of talazoparib plus avelumab at a fixed dose of 800mg IV Q2W are 
administered during the Phase 1b to define the RP2D for the combination. As of May 18, 
2018 among 12 patients enrolled at dose level D0 (talazoparib 1.0mg PO QD, avelumab 
800mg IV Q2W) in 3 sequential cohorts (n=9 CRPC; n=2 TNBC, n=1 ovarian cancer) that 
completed the DLT monitoring period and were evaluable for DLT only 1 SAE of anemia 
was reported, with no G3 AEs other than hematologic toxicities and no Grade 4-5 AEs. 
Therefore, the RP2D for the talazoparib/avelumab combination was talazoparib 1 mg PO 
QD days 1-28 and avelumab 800mg IV Q2W. Phase 2 enrollment opened on June 01, 
2018 and is ongoing (communication with Pfizer).  
 
2.6 
Inclusion of Women and Minorities and Planned Enrollment Report 
 
This study was designed to include women and minorities but was not designed to measure 
differences of intervention effects.  The anticipated accrual in the ethnicity/race and sex 
categories is shown in the table below.  
 
 


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DOMESTIC PLANNED ENROLLMENT REPORT 
Racial 
Categories 
Ethnic Categories 
Total 
Not Hispanic or Latino 
Hispanic or Latino 
Female 
Male 
Female 
Male 
American 
Indian/ 
Alaska Native 
0 
0 
0 
0 
0 
Asian 
0 
1 
0 
0 
1 
Native 
Hawaiian or 
Other Pacific 
Islander 
0 
0 
0 
0 
0 
Black or 
African 
American 
1 
2 
0 
0 
3 
White 
17 
21 
1 
1 
40 
More Than 
One Race 
0 
0 
0 
0 
0 
Total 
18 
24 
1 
1 
44 
 
 
3.0 
DRUG INFORMATION 
 
Investigator Brochures  
 
For information regarding Investigator Brochures, please refer to SWOG Policy 15. 
 
For this sub-study, talazoparib and avelumab are investigational and are being provided under an 
IND held by SWOG.  For INDs filed by SWOG, the protocol serves as the Investigator Brochure for 
the performance of the protocol. In such instances submission of the protocol to the IRB should 
suffice for providing the IRB with information about the drug. However, in cases where the IRB 
insists on having the official Investigator’s Brochure from the company, requests may be submitted 
to the CTSU website by completing the CTSU Request for Clinical Brochure.  
 
3.1 
Talazoparib (PF-06944076) (NSC 771561) (IND143217) 
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: Talazoparib is a highly potent and specific inhibitor of 
PARP1 and 2 with activity in tumor cell lines bearing DNA repair deficiencies. 
Treatment with a PARP inhibitor results in cell cycle arrest and apoptosis. 
 
b. 
PHARMACOKINETICS 
 
1. 
Absorption: Absorption of talazoparib is rapid and peak concentrations 
were generally achieved 1 to 8 hours post dose. At steady state, the mean 
Cmax was 21 ng/mL, the mean plasma trough concentration (Cmin) was 
3.72 ng/mL, the mean AUC was 202 ng●h/mL, and the mean peak-to-
trough ratio was approximately 6 hours. Food delays absorption of 
talazoparib but has no effect on the extent of absorption.   
 
2. 
Distribution: Protein binding of talazoparib is 78.7% in human plasma. The 
apparent volume of distribution (V/F) decreases with increasing doses. At 
1000 mcg/day, the mean V/F is 415 L. After repeated administration at 


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1000 mcg/day, talazoparib accumulated approximately 2.4-fold relative to 
a single dose.  
 
3. 
Metabolism: Overall, talazoparib is largely cleared via excretion of 
unchanged parent drug and metabolized to a minor extent via oxidation 
and dehydrogenation. 
 
4. 
Elimination:  Elimination follows biphasic kinetics, with a mean half-life 
ranging from 52.9 to 229 hours. Renal excretion is a major elimination 
pathway for unchanged parent talazoparib. Following oral administration, 
44 to 90.6% of the dose was recovered in the urine as unchanged parent 
drug.   
 
c. 
ADVERSE EFFECTS  
 
1. 
Adverse Effects:  
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. Refer to the 'CTEP, NCI Guidelines: Adverse Event Reporting 
Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/
aeguidelines.pdf for further clarification. Frequency is provided based on 
553 patients. Below is the CAEPR for Talazoparib (MDV3800, BMN 673). 
 
Version 2.4, October 24, 20201 
 
 Adverse Events with Possible  
 Relationship to Talazoparib (MDV3800, BMN 673) 
 (CTCAE 5.0 Term) 
[n= 553] 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
Anemia 
 
 
 
 
Febrile neutropenia 
GASTROINTESTINAL DISORDERS 
 
Abdominal pain 
 
 
Constipation 
 
Diarrhea 
 
 
 
Dyspepsia 
 
 
Mucositis oral 
 
Nausea 
 
 
Vomiting 
 
 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
Fatigue 
 
 
 
Fever 
 
 
Pain 
 
INFECTIONS AND INFESTATIONS 
 
Infection2 
 
INVESTIGATIONS 
 
Lymphocyte count 
decreased 
 
Neutrophil count 
decreased 
 
 


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 Adverse Events with Possible  
 Relationship to Talazoparib (MDV3800, BMN 673) 
 (CTCAE 5.0 Term) 
[n= 553] 
Likely (>20%) 
Less Likely (<=20%) 
Rare but Serious (<3%) 
Platelet count 
decreased 
 
 
 
White blood cell 
decreased 
 
METABOLISM AND NUTRITION DISORDERS 
 
Anorexia 
 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND 
POLYPS) 
 
 
Leukemia secondary to 
oncology chemotherapy 
 
 
Myelodysplastic 
syndrome 
 
 
Treatment related 
secondary malignancy 
NERVOUS SYSTEM DISORDERS 
 
Dizziness 
 
Headache 
 
 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
Alopecia 
 
 
 
1This 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. 
 
2Infection may include any of the 75 infection sites under the 
INFECTIONS AND INFESTATIONS SOC. 
 
3Neuropathy peripheral may include both Peripheral sensory neuropathy 
and Peripheral motor neuropathy under the NERVOUS SYSTEM 
DISORDERS SOC. 
 
 
Adverse events reported on talazoparib (MDV3800, BMN 673) trials, 
but for which there is insufficient evidence to suggest that there 
was a reasonable possibility that talazoparib (MDV3800, BMN 673) 
caused the adverse event: 
 
BLOOD AND LYMPHATIC SYSTEM DISORDERS - Blood and 
lymphatic system disorders - Other (pancytopenia) 
CARDIAC DISORDERS - Atrial flutter; Sinus bradycardia 
GASTROINTESTINAL DISORDERS - Abdominal distension; Flatulence; 
Intra-abdominal hemorrhage; Small intestinal obstruction; Toothache 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - 
Edema limbs; General disorders and administration site conditions - 
Other (accidental overdose); Non-cardiac chest pain 


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HEPATOBILIARY DISORDERS - Hepatic failure; Sinusoidal obstruction 
syndrome 
INVESTIGATIONS - Alanine aminotransferase increased; Aspartate 
aminotransferase increased; Weight loss 
METABOLISM AND NUTRITION DISORDERS - Hyperkalemia; 
Hypokalemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - 
Arthralgia; Back pain; Generalized muscle weakness; Muscle cramp; 
Myalgia; Neck pain; Pain in extremity 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL 
CYSTS AND POLYPS) - Neoplasms benign, malignant and unspecified 
(incl cysts and polyps) - Other (glioblastoma multiforme); Neoplasms 
benign, malignant and unspecified (incl cysts and polyps) - Other 
(metastases to meninges); Neoplasms benign, malignant and 
unspecified (incl cysts and polyps) - Other (metastatic breast cancer) 
NERVOUS SYSTEM DISORDERS - Dysgeusia; Intracranial 
hemorrhage; Nervous system disorders - Other (neuropathy peripheral)3; 
Nervous system disorders - Other (nonserious axonal sensorimotor 
polyneuropathy); Syncope; Transient ischemic attacks 
PSYCHIATRIC DISORDERS - Anxiety; Insomnia; Psychiatric disorders - 
Other (mental status changes) 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - 
Cough; Dyspnea; Epistaxis; Oropharyngeal pain; Pleural effusion; 
Respiratory, thoracic and mediastinal disorders - Other (obstructive 
airways disorder) 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Dry skin; Rash 
maculo-papular 
VASCULAR DISORDERS - Thromboembolic event 
 
 
Note: Talazoparib (MDV3800, BMN 673) 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. 
 
2. 
Pregnancy and Lactation: 
 
Studies in pregnant animals to evaluate the effect of talazoparib on 
pregnancy have not been performed. Women of childbearing potential 
should use highly effective contraceptive measures during and for at least 
7 months after completion of treatment. Non-sterilized males who are 
sexually active with a female partner should use highly effective 
contraceptive measures during and for at least 4 months after completion 
of treatment. Male patients must not make sperm donations during 
treatment and for 4 months following the last dose of treatment. 
 
Studies in lactating animals to evaluate the effect of talazoparib have not 
been performed. It is not known whether talazoparib is excreted in human 
milk. Therefore, breastfeeding should be stopped during talazoparib 
treatment. 
 
3. 
Drug Interactions:  
 


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Talazoparib does not inhibit or induce CYP450 isoenzymes. Therefore, 
drug-drug interactions related to CYP450 inhibition or induction are 
unlikely to be clinically significant.  
 
Talazoparib is a substrate for P-gp and BCRP, and plasma talazoparib 
concentrations may increase or decrease when co-administered with P-
gp or BCRP inhibitors or inducers, respectively. Guidelines for 
concomitant use of talazoparib with inhibitors or inducers of P-gp or 
inhibitors of BCRP are as follows:  
 
• 
Use of strong P-gp inhibitors (e.g., dronedarone, quinidine, 
ranolazine, verapamil, oral ketoconazole, itraconazole), P-gp 
inducers (e.g., rifampin, tipranavir/ritonavir), or BCRP inhibitors 
(e.g., elacridar [GF120918]) should be avoided.  
 
Caution should be used for coadministration of other P-gp inhibitors (e.g., 
amiodarone, 
azithromycin, 
captopril, 
carvedilol, 
clarithromycin, 
conivaptan, cyclosporine, diltiazem, erythromycin, felodipine, lopinavir, 
quercetin), P-gp inducers (e.g., avasimibe, carbamazepine, phenytoin, St 
John’s wort), or BCRP inhibitors (e.g., cyclosporine, eltrombopag, and 
gefitinib). 
 
Please note that this list is not all-inclusive. Because lists of these agents 
are constantly changing, it is important to regularly consult a frequently 
updated list for the most up-to-date listing of agents; medical reference 
texts such as the Physicians’ Desk Reference may also provide this 
information. 
https://www.fda.gov/drugs/drug-interactions-labeling/drug-development-
and-drug-interactions  
 
d. 
DOSING & ADMINISTRATION 
 
See Section 7.0 Treatment Plan. 
 
e. 
HOW SUPPLIED 
 
1. 
Talazoparib is supplied by Pfizer and distributed by Pharmaceutical 
Management Branch (PMB). 
 
Talazoparib is a capsule formulation comprised of a blend of talazoparib 
tosylate drug substance and silicified microcrystalline cellulose filled into a 
hypromellose capsule. It is supplied as 1000 mcg (opaque pale-pink, size 
4) and 250 mcg (opaque white, size 4) capsules supplied in 30-count high-
density polyethylene (HDPE) bottles with induction-sealed closures. 
 
f. 
STORAGE, PREPARATION & STABILITY 
 
1. 
Store talazoparib at room temperature (15-30 ºC; 59-86 ºF). Contact Pfizer 
for temperature excursion information.  
 
If a storage temperature excursion is identified, do not use the affected 
investigational product. The investigational product must be stored 
separately in an appropriate location pending the final disposition decision. 
Return the investigational product that underwent the temperature 
excursion in the appropriate storage conditions and quarantine until a 
suitable determination is made.  In case of temperature excursion at the 


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site outside of storage range, complete the Site Temperature Excursion 
Report 
Form 
(see 
Appendix 
18.6) 
and 
email 
to 
GCSTempExcursionSupport@pfizer.com. In the email correspondence, 
reference the Pfizer tracking number for this study: WI247821.  
 
Talazoparib is considered a cytotoxic agent; precautions regarding 
appropriate secure storage and handling must be used by healthcare 
professionals, including personal protective clothing, disposable gloves, 
and equipment. Patients should be advised that oral anticancer agents are 
toxic substances and the patient and caregivers should always use gloves 
when handling capsules. For additional patient instructions, see Section 
7.4. 
 
3.2 
Avelumab (MSB0010718C; Bavencio®) (NSC 799232) (IND 143217) 
 
a. 
PHARMACOLOGY 
 
Mechanism of Action: Avelumab binds PD-L1 and blocks the interaction between 
PD-L1 and PD-1. This removes the suppressive effects of PD-L1 on antitumor 
CD8+ T cells, resulting in the restoration of cytotoxic T cell response. 
 
b. 
PHARMACOKINETICS 
 
Absorption: Avelumab is administered intravenously and is 100% bioavailable. 
 
Distribution: Avelumab is expected to be distributed in the systemic circulation and 
to a lesser extent into the extracellular space. In vitro studies suggest that 
avelumab binds to human tissues that are known for PD-L1 expression: various 
epithelial cell types, endothelium, mononuclear cells (including dendritic cells, 
lymphocytes, monocytes and macrophages), pancreatic islets, placental 
trophoblasts and decidual cells, smooth muscle cells, and mesenchymal stem 
cells.  The volume of central and peripheral compartments is estimated to be 2.84L 
and 1.21L in the typical patient, respectively. The geometric mean Vss for a patient 
receiving 10mg/kg was 4.72L, which is consistent with distribution mainly limited 
to systemic circulation. 
 
Metabolism: Avelumab is degraded by proteolytic catabolism. CYP450 does not 
contribute to its metabolism. 
 
Elimination: The primary route of elimination of avelumab is through proteolytic 
degradation. The geometric mean clearance calculated by noncompartmental 
analyses [Study EMR100070-001] was estimated as 0.362mL/hr/kg for an initial 
10mg/kg/dose. The corresponding value for Japanese patients [Study 
EMR100070-002] was calculated as 0.471mL/hr/kg at the 10mg/kg dose. The 
estimate of clearance obtained for a typical patient in population pharmacokinetic 
analysis 
was 
0.0246 
L/hr. 
Population 
pharmacokinetic 
analysis 
and 
noncompartmental analysis results are comparable. 
 
c. 
ADVERSE EFFECTS 
 
1. 
Adverse Effects: The Comprehensive Adverse Events and Potential Risks 
list (CAEPR) provides a single list of reported and/or potential adverse 


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events (AE) associated with an agent using a uniform presentation of 
events by body system. Refer to the 'CTEP, NCI Guidelines: Adverse 
Event 
Reporting 
Requirements' 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/
aeguidelines.pdf for further clarification.  
Frequency is provided based on 1738 patients. Below is the CAEPR for 
Avelumab. 
Version 2.0, April 23, 20191 
Adverse Events with Possible Relationship  
to Avelumab 
(CTCAE 5.0 Term) 
[n=1738] 
Likely 
(> 20%) 
Less Likely 
(4 - ≤ 20%) 
Rare but Serious  
(≤ 3%) 
BLOOD AND LYMPHATIC SYSTEM DISORDERS 
 
Anemia 
 
CARDIAC DISORDERS 
 
 
Myocarditis2 
 
 
Pericarditis2 
ENDOCRINE DISORDERS 
 
 
Adrenal insufficiency2 
 
 
Hyperthyroidism2 
 
 
Hypophysitis2 
 
 
Hypopituitarism2 
 
Hypothyroidism2 
 
EYE DISORDERS 
 
 
Uveitis2 
GASTROINTESTINAL DISORDERS 
 
Abdominal pain 
 
 
 
Colitis2 
 
Diarrhea 
 
 
Nausea 
 
 
Pancreatitis2 
 
 
Vomiting 
 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 
 
Chills 
 
Fatigue 
 
 
 
Fever 
 
 
Flu like symptoms3 
 
HEPATOBILIARY DISORDERS 
 
 
Hepatic failure2 
 
 
Hepatobiliary disorders 
- Other (autoimmune 
hepatitis, immune-
related hepatitis)2 
IMMUNE SYSTEM DISORDERS 
 
 
Autoimmune disorder2 
 
 
Cytokine release 
syndrome3 
 
 
Immune system 
disorders - Other 
(sarcoidosis)2 
INFECTIONS AND INFESTATIONS 
 
Infection4 
 


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Adverse Events with Possible Relationship  
to Avelumab 
(CTCAE 5.0 Term) 
[n=1738] 
Likely 
(> 20%) 
Less Likely 
(4 - ≤ 20%) 
Rare but Serious  
(≤ 3%) 
INJURY, POISONING AND PROCEDURAL COMPLICATIONS 
 
Infusion related reaction3 
 
INVESTIGATIONS 
 
Alanine 
aminotransferase 
increased 
 
 
Alkaline phosphatase 
increased 
 
 
Aspartate 
aminotransferase 
increased 
 
 
Blood bilirubin increased 
 
 
CPK increased 
 
 
Creatinine increased 
 
 
GGT increased 
 
 
Lipase increased 
 
 
Lymphocyte count 
decreased 
 
 
Neutrophil count 
decreased 
 
 
Platelet count decreased 
 
 
Serum amylase 
increased 
 
 
Thyroid stimulating 
hormone increased 
 
METABOLISM AND NUTRITION DISORDERS 
 
Anorexia 
 
 
 
Hyperglycemia2 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 
 
Arthralgia2 
 
 
Generalized muscle 
weakness 
 
 
Muscle cramp 
 
 
Myalgia2 
 
 
 
Myositis2 
 
Pain in extremity 
 
NERVOUS SYSTEM DISORDERS 
 
 
Encephalopathy2 
 
 
Guillian-Barre 
syndrome2 
 
 
Myasthenia gravis2 
 
 
Nervous system 
disorders - Other (non-
infectious 
encephalitis)2 
 
 
Nervous system 
disorders - Other (non-
infectious meningitis)2 
 
 
Peripheral motor 
neuropathy 
 
 
Peripheral sensory 
neuropathy2 


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Adverse Events with Possible Relationship  
to Avelumab 
(CTCAE 5.0 Term) 
[n=1738] 
Likely 
(> 20%) 
Less Likely 
(4 - ≤ 20%) 
Rare but Serious  
(≤ 3%) 
RENAL AND URINARY DISORDERS 
 
 
Renal and urinary 
disorders - Other 
(immune related 
nephritis)2 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 
 
Cough 
 
 
 
Pneumonitis2 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS 
 
Eczema 
 
 
Pruritus 
 
 
Rash acneiform 
 
 
Rash maculo-papular 
 
 
1This 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. 
 
2Immune-mediated adverse reactions have been reported in patients 
receiving avelumab.  Adverse events potentially related to avelumab may 
be manifestations of immune-mediated adverse events. In clinical trials, 
most immune-mediated adverse reactions were reversible and managed 
with interruptions of avelumab), administration of corticosteroids and 
supportive care. 
 
3Infusion reactions, including high-grade hypersensitivity reactions, 
anaphylaxis, and cytokine release syndrome, which have been observed 
following administration of avelumab, may manifest as fever, chills, shakes, 
itching, rash, hypertension or hypotension, or difficulty breathing during and 
immediately after administration of avelumab. 
 
4Infection includes all 75 sites of infection under the INFECTIONS AND 
INFESTATIONS SOC. 
  
Adverse events reported on avelumab trials, but for which there is 
insufficient evidence to suggest that there was a reasonable 
possibility that avelumab caused the adverse event: 
 
CARDIAC DISORDERS - Palpitations; Sinus tachycardia 
EYE DISORDERS - Blurred vision; Dry eye 
GASTROINTESTINAL DISORDERS - Abdominal distension; Constipation; 
Dry mouth; Dyspepsia; Flatulence; Mucositis oral 
GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS - 
Edema limbs; Localized edema; Malaise; Non-cardiac chest pain; Pain 
INVESTIGATIONS - Electrocardiogram QT corrected interval prolonged; 
Investigations - Other (c-reactive protein increased); Weight gain; Weight 
loss 


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METABOLISM 
AND 
NUTRITION 
DISORDERS 
- 
Dehydration; 
Hypoalbuminemia; 
Hypokalemia; 
Hypomagnesemia; 
Hyponatremia; 
Hypophosphatemia 
MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS - Back 
pain; Bone pain 
NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS 
AND POLYPS) - Neoplasms benign, malignant and unspecified (incl cysts 
and polyps) - Other (tumor flare); Tumor pain 
NERVOUS SYSTEM DISORDERS - Dizziness; Dysesthesia; Dysgeusia; 
Headache; Tremor 
RENAL AND URINARY DISORDERS - Proteinuria 
RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS - 
Dyspnea; Hypoxia 
SKIN AND SUBCUTANEOUS TISSUE DISORDERS - Alopecia; Dry skin; 
Hyperhidrosis 
VASCULAR DISORDERS - Flushing; Hot flashes; Hypertension 
 
Note: Avelumab 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. 
 
2. 
Pregnancy and Lactation: Based on its mechanism of action, avelumab 
can cause fetal harm when administered to a pregnant woman. Advise 
females of reproductive potential to use effective contraception during 
treatment with avelumab and for at least one month after the last dose of 
avelumab.  There is no information regarding the presence of avelumab in 
human milk, the effects on the breastfed infant or the effects on milk 
production. Since many drugs including antibodies are excreted in human 
milk, advise lactating women not to breastfeed during treatment and for at 
least one month after the last dose of avelumab due to the potential for 
serious adverse reactions in breastfed infants.  
 
3. 
Special Populations: No dedicated clinical studies have been conducted 
to evaluate the effect of renal or hepatic impairment on the 
pharmacokinetics of avelumab. Even though a limited number of patients 
with severe renal impairment have been studies, renal impairment is not 
expected to have an effect on the pharmacokinetics of avelumab. here are 
limited data from patients with severe hepatic impairment, and the effect 
of severe hepatic impairment on the pharmacokinetics of avelumab is not 
known.  
 
4. 
Drug Interactions: No interaction studies have been conducted with 
avelumab in humans. 
 
d. 
DOSING & ADMINISTRATION 
See Section 7.0 Treatment Plan. 
 
e. 
HOW SUPPLIED 
 
Avelumab is supplied by Merck KGaA/EMD Serono, Inc./Pfizer and distributed by 
the Pharmaceutical Management Branch, CTEP/DCTD/NCI as single-use 200 mg 
vials containing a sterile solution of 10 mL total volume (20 mg/ml).  Avelumab is 
a clear and colorless to slightly yellow concentrate for solution containing D-
mannitol, glacial acetic acid, polysorbate 20, sodium hydroxide, and water for 
injection, and supplied in glass vials closed with a rubber (not made with natural 


S1900C 
 
 
Page 24 
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rubber latex) stopper and sealed with an aluminum crimp seal closure fitted with a 
removable plastic cap.  
 
f. 
STORAGE, PREPARATION & STABILITY 
 
1. 
Avelumab must be stored under refrigeration (2-8 C, 36-46º F) and 
protected from light until use. Avelumab must not be frozen. Rough 
shaking must be avoided during handling and preparation.  
 
2. 
Prepare avelumab solution under a laminar flow hood using aseptic 
technique. If a laminar flow hood is not available, alternative procedures 
and 
aseptic 
handling 
techniques 
that 
prevent 
microbiological 
contamination may be used.  
 
3. 
Prior to preparation of the dilution for infusion, allow vial(s) to equilibrate 
to room temperature. The measured dose should be diluted with 250 mL 
0.9% Sodium Chloride or 0.45% Sodium Chloride solution. Gently invert 
the mixture 10 times. Do not shake infusion bag in order to avoid foaming 
and/or excessive shearing of the protein solution. Carefully inspect the 
prepared dose to confirm homogeneity of the solution and that it is free of 
any visible particles or discoloration. 
 
4. 
Prepared solutions of avelumab should be used immediately. If not used 
immediately, diluted avelumab may be stored for up to 4 hours at room 
temperature (15C-25C) or up to 24 hours under refrigeration (2C to 
8C); this includes infusion time. Note that the time interval for stability 
begins at the time the intact avelumab vials are removed from the 
refrigerator and allowed to reach room temperature for dose preparation. 
If finished doses are stored under refrigeration, allow the bag containing 
avelumab to come to room temperature. 
If a storage temperature excursion is identified, do not use the affected 
investigational product. The investigational product must be stored 
separately in an appropriate location pending the final disposition decision. 
In case of temperature excursion at the site outside of storage range, 
complete the Site Temperature Excursion Report Form (see Appendix 
18.6) and email to GCSTempExcursionSupport@pfizer.com. In the email 
correspondence, reference the Pfizer tracking number for this study: 
WI247821. 
 
5. 
No other drugs should be added to the solution of avelumab for infusion. 
 
6. 
Administer diluted avelumab solution through infusion tubing with a sterile, 
non-pyrogenic, low protein binding, 0.2-micron in-line filter. Do not co-
administer other drugs through the same IV line. 
  
3.3 
NCI-Supplied Agent Ordering and Agent Accountability 
 
NCI-supplied agents may be requested by eligible participating Investigators (or their 
authorized designee) at each participating institution. The CTEP assigned protocol number 
(S1900C) 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 participating investigator at 
that institution. 


S1900C 
 
 
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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. For 
questions about drug orders, transfers, returns, or accountability, call or email PMB any 
time. Refer to the PMB’s website for specific policies and guidelines related to agent 
management. 
 
No starter supplies may be ordered. Patients must be enrolled and registered to protocol 
S1900C prior to order submission through OAOP.  
 
Useful Links and Contacts 
• 
CTEP Forms, Templates, Documents:  http://ctep.cancer.gov/forms/  
• 
NCI CTEP Investigator Registration (RCR) Help Desk:  RCRHelpDesk@nih.gov  
• 
PMB policies and guidelines: 
http://ctep.cancer.gov/branches/pmb/agent_management.htm  
• 
PMB Online Agent Order Processing (OAOP) application:   
https://ctepcore.nci.nih.gov/OAOP/ 
• 
CTEP Identity and Access Management (IAM) account:   
https://ctepcore.nci.nih.gov/iam/index.jsp  
• 
CTEP IAM account help:   
ctepreghelp@ctep.nci.nih.gov  
• 
PMB e-mail:  PMBAfterHours@mail.nih.gov  
 
PMB phone and hours of service:  240/276-6575 Monday through Friday between 8:30 am 
and 4:30 pm (ET) 
 
a. 
Drug Return and/or Disposition Instruction  
 
1. 
Drug Returns: All unused drug supplies must be returned to the PMB. 
When it is necessary to return study drug (e.g., sealed vials remaining 
when expired vials are recalled by the PMB), 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).  
 
2. 
Drug Accountability: The investigator, or a responsible party designated 
by the investigator, must maintain a careful record of the receipt, 
disposition, and return of all drugs received from the PMB using the 
appropriate NCI Investigational Agent  (Drug) Accountability Record  
(DARF)  available on the CTEP forms page.  Store and maintain separate 
NCI Investigational Agent Accountability Records for each agent, strength, 
formulation and ordering investigator in this protocol. 
 
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. 
 
  
4.0 
STAGING CRITERIA 
 
Patients must have Stage IV or recurrent disease as outlined below (AJCC Cancer Staging Manual, 
8th Edition, 2017): 
 
Stage IVA 
Any T Any N M1a 
 
 
Any T Any N M1b 
 
Stage IVB 
Any T Any N M1c 


S1900C 
 
 
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Primary Tumor (T) 
 
TX 
Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in 
sputum or bronchial washings but not visualized by imaging or bronchoscopy 
T0 
No evidence of primary tumor 
Tis 
Carcinoma in situ 
Adenocarcinoma in situ (AIS): adenocarcinoma with pure lepidic pattern, ≤ 3 cm in 
greatest dimension 
T1 
Tumor ≤ 3 cm in greatest dimension, surrounded by lung or visceral pleura, without 
bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e., not in the 
main bronchus) 
T1mi 
Minimally invasive adenocarcinoma: adenocarcinoma (≤ 3 cm in greatest dimension) with 
a predominantly lepidic pattern and ≤ 5 mm invasion in greatest dimension 
T1a 
Tumor ≤ 1 cm in greatest dimension. A superficial, spreading tumor of any size whose 
invasive component is limited to the bronchial wall and may extend proximal to the main 
bronchus also is classified as T1a, but these tumors are uncommon.  
T1b 
Tumor ˃ 1 cm but ≤ 2 cm in greatest dimension 
T1c 
Tumor ˃ 2 cm but ≤ 3 cm in greatest dimension 
T2 
Tumor ˃ 3 cm but ≤ 5 cm or having any of the following features: 
• Involves the main bronchus regardless of distance to the carina, but without 
involvement of the carina 
• 
Invades visceral pleura (PL1 or PL2) 
• Associated with atelectasis or obstructive pneumonitis that extends to the hilar 
region, involving part or all of the lung 
T2 tumors with these features are classified as T2a if ≤ 4 cm or if the size cannot be 
determined and T2b if ˃ 4 cm but ≤ 5 cm. 
T2a 
Tumor ˃ 3 cm but ≤ 4 cm in greatest dimension 
T2b 
Tumor ˃4 cm but ≤ 5 cm in greatest dimension 
T3 
Tumor ˃ 5 cm but ≤ 7 cm in greatest dimension or directly invading any of the following:  
parietal pleural (PL3), chest wall (including superior sulcus tumors), phrenic nerve, parietal 
pericardium, or separate tumor nodule(s) in the same lobe as the primary 
T4 
Tumor ˃ 7 cm or tumor of any size invading one or more of the following:  diaphragm, 
mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, 
vertebral body, or carina; separate tumor nodule(s) in an ipsilateral lobe different from that 
of the primary 
 
Regional Lymph Nodes (N) 
 
NX 
Regional lymph nodes cannot be assessed 
N0 
No regional lymph node metastases 
N1 
Metastasis in ipsilateral peribronchial and/or ipsilateral hilar lymph nodes and 
intrapulmonary nodes, including involvement by direct extension 
N2 
Metastasis in ipsilateral mediastinal and/or subcarinal lymph node(s) 
N3 
Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral 
scalene, or supraclavicular lymph node(s)  
 
Distant Metastasis (M) 
 
M0 
No distant metastasis 
M1 
Distant metastasis 
M1a 
Separate tumor nodule(s) in a contralateral lobe; tumor with pleural or malignant pleural or 
pericardial effusion. nodules or malignant pleural (or pericardial) effusion. ** 
M1b 
Single extrathoracic metastasis in a single organ (including involvement of a single 
nonregional node) 
M1c 
Multiple extrathoracic metastases in a single organ or in multiple organs 


S1900C 
 
 
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** 
Most pleural (and pericardial) effusions with lung cancer are due to tumor.  In a few 
patients, however, multiple microscopic examinations of pleural (pericardial) fluid are 
negative for tumor, and the fluid is non-bloody and is not an exudate.  If these elements 
and clinical judgment dictate that the effusion is not related to the tumor, the effusion should 
be excluded as a staging descriptor. 
 
 
5.0 
ELIGIBILITY CRITERIA 
 
Each of the criteria in the following section must be met in order for a patient to be considered 
eligible for registration in OPEN.  Section 5 may be printed and used to by the site, but is not to be 
uploaded in RAVE (unless specially stated). For each criterion requiring test results and dates, 
please record this information on the Onstudy Form and submit via Medidata Rave® (see Section 
14.0).  Any potential eligibility issues should be addressed to the SWOG Statistics and Data 
Management Center (SDMC) in Seattle at 206/652-2267 or LUNGMAPQuestion@crab.org prior to 
registration. NCI policy does not allow for waiver of any eligibility criterion  
(http://ctep.cancer.gov/protocolDevelopment/policies_deviations.htm). 
 
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 4 weeks later would be 
considered Day 28.  This allows for efficient patient scheduling without exceeding the guidelines.  
If Day 7, 14, 16, 28, or 42 falls on a weekend or holiday, the limit may be extended to the next 
working day. 
 
5.1 
Disease Related Criteria 
 
a. 
Patients must be assigned to S1900C. Assignment to S1900C is determined by 
the LUNGMAP protocol genomic profiling using the FoundationOne assay. 
Biomarker eligibility for S1900C is based on the identification of a pathogenic 
somatic mutation in STK11 or STK11 bi-allelic loss on tumor. 
 
b. 
Patients must have histologically or cytologically confirmed Stage IV or recurrent 
non-squamous, 
mixed 
squamous/non-squamous 
(e.g., 
adeno-squamous 
carcinoma), or non-small cell lung cancer not otherwise specified (NSCLC NOS). 
Patients with pure squamous cell carcinoma are not eligible. 
 
 
c. 
Patients with evidence of chronic hepatitis B virus (HBV) infection must have 
undetectable HBV viral load on suppressive therapy within 28 days prior to sub-
study registration.  
 
d. 
Patients with a history of hepatitis C virus (HCV) infection must have been treated 
and cured. Patients with HCV infection who are currently on treatment must have 
an undetectable HCV viral load within 28 days prior to sub-study registration. 
 
e. 
Patients with known human immunodeficiency virus (HIV) infection are eligible, 
provided they are on effective anti-retroviral therapy and have undetectable viral 
load at their most recent viral load test and within 6 months prior to sub-study 
registration. 
 
f. 
Patients must not have EGFR sensitizing mutations, EGFR T790M mutation, ALK 
gene fusion, ROS 1 gene rearrangement, and BRAF V600E mutation unless they 
have progressed following all standard of care targeted therapy. 
 


S1900C 
 
 
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5.2 
Prior/Concurrent Therapy Criteria 
 
a. 
Patients must have received at least one line of anti-PD-1 or anti-PD-L1 therapy 
for Stage III, IV or recurrent disease.  
 
Any number of additional, non-platinum-based chemotherapy or targeted therapy 
regimens for recurrent or metastatic disease are allowed. 
 
1. 
Patients may not have received more than one line of anti-PD-1 or anti-
PD-L1 therapy in the Stage IV or recurrent setting. Anti-PD-1 or anti-PD-
L1 therapy may have been given alone or in combination with platinum-
based chemotherapy, an anti-CTLA4 therapy, or other immune-
modulatory 
therapy. 
Patients 
must 
have 
experienced 
disease 
progression>42 days following initiation (Cycle 1 Day 1) of the anti-PD-1 
or anti-PD-L1 containing regimen.  
 
2. 
Patients, must have received prior platinum-based chemotherapy and 
experienced disease progression >42 days following initiation (Cycle 1 
Day 1) of platinum based chemotherapy. Note: Patients may have 
received this in combination with anti-PD-1 or anti-PD-L1. 
 
3. 
Patients who received anti-PD-1 or anti-PD-L1 therapy following 
concurrent chemoradiation for Stage III disease as their only line of anti-
PD-1 or anti-PD-L1 therapy, are eligible if they experienced disease 
progression less than (<) 365 days from the date of initiation of anti-PD-1 
or anti-PD-L1 therapy.   
 
b. 
Patients who received prior adjuvant platinum-based therapy post-surgical 
resection for Stage I-III disease (i.e. the patient has not received platinum-based 
chemotherapy for Stage IV or recurrent disease) must have had disease 
progression during or after platinum-based chemotherapy that occurred less than 
(<) 365 days from the last date that the patient received that therapy. 
 
c. 
Patients must be able to swallow capsules whole. 
 
d. 
Patients must not have had prior exposure to any agent with a PARP inhibitor (e.g., 
veliparib, olaparib, rucaparib, niraparib, talazoparib) as its primary pharmacology.  
 
e. 
Patients must not be taking, nor plan to take while on protocol treatment strong P-
gp inhibitors, P-gp inducers, or strong breast cancer resistance protein (BCRP) 
inhibitors. Please refer section 3.1 c. for detailed information. 
 
f. 
Patients must have progressed (in the opinion of the treating physician) following 
their most recent line of therapy. 
 
g. 
Patients must not have received prior systemic immunotherapy within 28 days prior 
to sub-study registration and must not have received any prior systemic therapy 
(including systemic chemotherapy or investigational drug) within 21 days prior to 
sub-study registration. Patients must have recovered (≤ Grade 1) from any side 
effects of prior therapy. Patients must not have received any radiation therapy 
within 14 days prior to sub-study registration. (See 5.3b for criteria regarding 
therapy for CNS metastases). 
 


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h. 
Patients must not be planning to receive any concurrent chemotherapy, 
immunotherapy, biologic or hormonal therapy for cancer treatment while receiving 
treatment on this study. Concurrent use of hormones for non-cancer-related 
conditions (e.g., insulin for diabetes and hormone replacement therapy) is 
acceptable. 
 
5.3 
Clinical/Laboratory Criteria 
 
a. 
Patients must have measurable disease (Section 10.1) documented by CT or MRI. 
The CT from a combined PET/CT may be used to document only non-measurable 
disease unless it is of diagnostic quality as defined in Section 10.1c. Measurable 
disease must be assessed within 28 days prior to sub-study registration. Pleural 
effusions, ascites and laboratory parameters are not acceptable as the only 
evidence of disease. Non-measurable disease must be assessed within 42 days 
prior to sub-study registration. All disease must be assessed and documented on 
the Baseline Tumor Assessment Form. Patients whose only measurable disease 
is within a previous radiation therapy port must demonstrate clearly progressive 
disease (in the opinion of the treating investigator) prior to sub-study registration. 
See Sections 15.5 and Appendix 18.2 for guidelines and submission instructions 
for required central radiology review. CT and MRI scans must be submitted for 
central review via TRIAD. 
 
b. 
Patients must have a CT or MRI scan of the brain to evaluate for CNS disease 
within 42 days prior to sub-study registration. Patient must not have 
leptomeningeal disease, spinal cord compression or brain metastases unless: (1) 
metastases have been locally treated and have remained clinically controlled and 
asymptomatic for at least 14 days following treatment, and prior to sub-study 
registration, AND (2) patient has no residual neurological dysfunction and has 
been off corticosteroids for at least 24 hours prior to sub-study registration. 
 
c. 
Patient must not have had a major surgery within 14 days prior to sub-study 
registration. Patient must have fully recovered from the effects of prior surgery in 
the opinion of the treating investigator. 
 
d. 
Patients must have adequate hepatic function as defined by serum bilirubin ≤ 
Institutional Upper Limit of Normal (IULN) and either ALT or AST ≤ 2 x IULN within 
28 days prior to sub-study registration (if both ALT and AST are done, both must 
be ≤ 2 IULN). For patients with liver metastases, bilirubin and either ALT or AST 
must be ≤ 5 x IULN (if both ALT and AST are done, both must be ≤ 5 x IULN). 
 
e. 
Patients must have a serum creatinine ≤ the IULN or calculated creatinine 
clearance ≥ 60 mL/min using the following Cockroft-Gault Formula. This specimen 
must have been drawn and processed within 28 days prior to sub-study 
registration: 
 
Calculated Creatinine Clearance = (140 - age) X (weight in kg) † 
    72 x serum creatinine* 
 
Multiply this number by 0.85 if the patient is a female.  
 
† The kilogram weight is the patient weight with an upper limit of 140% of the IBW. 
* Actual lab serum creatinine value with a minimum of 0.7 mg/ dL. 
 
Creatinine Calculator:  
https://crawb.crab.org/TXWB/CreatinineClearanceCalculator.aspx  
 


S1900C 
 
 
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f. 
Patients’ most recent Zubrod performance status must be 0-1 (Section 10.4) 
documented within 28 days prior to sub-study registration. 
 
g. 
Patients must not have any Grade III/IV cardiac disease as defined by the New 
York Heart Association Criteria (i.e., patients with cardiac disease resulting in 
marked limitation of physical activity or resulting in inability to carry on any physical 
activity without discomfort), unstable angina pectoris, and myocardial infarction 
within 6 months, or serious uncontrolled cardiac arrhythmia (Appendix 18.1). 
 
h. 
Pre-study history and physical exam must be obtained within 28 days prior to sub-
study registration. 
 
i. 
No other prior malignancy is allowed except for the following: adequately treated 
basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated 
Stage I or II cancer from which the patient is currently in complete remission, or 
any other cancer from which the patient has been disease free for five years. 
 
j. 
Patients must not be pregnant or nursing. Women/men of reproductive potential 
must have agreed to use an effective contraceptive method. A woman is 
considered to be of "reproductive potential" if she has had menses at any time in 
the preceding 12 consecutive months. In addition to routine contraceptive 
methods, "effective contraception" also includes heterosexual celibacy and 
surgery intended to prevent pregnancy (or with a side-effect of pregnancy 
prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal 
ligation. However, if at any point a previously celibate patient chooses to become 
heterosexually active during the time period for use of contraceptive measures 
outlined in the protocol, he/she is responsible for beginning contraceptive 
measures. 
 
k. 
Patients must not have a history of prior organ transplantation, including allogeneic 
stem-cell transplantation. 
 
l. 
Patients must not have received systemic treatment with corticosteroids (> 10 mg 
daily prednisone or equivalent) or other immunosuppressive medications within 14 
days prior to sub-study registration. Inhaled or topical steroids, and adrenal 
replacement doses ≤ 10 mg daily prednisone or equivalent are permitted in the 
absence of active autoimmune disease. 
 
m. 
Patients must not have active autoimmune disease that requires systemic steroids 
(equivalent of >10 mg of prednisone) or immunosuppressive agents within 14 days 
prior to sub-study registration (for example disease-modifying anti-rheumatic 
drugs). Exceptions include: patients with controlled type 1 diabetes mellitus, 
controlled hypo- or hyperthyroidism, vitiligo, resolved childhood asthma/atopy, or 
psoriasis not requiring immunosuppressive therapy. 
 
n. 
Patients must not have any impairment of gastrointestinal function or 
gastrointestinal disease that may significantly alter the absorption of talazoparib 
(e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption 
syndrome, small bowel resection, or active peptic ulcer disease). Note: peptic ulcer 
is considered non-active if clinically stable for 1 month.  
 
o. 
Patients must not have active small or large intestine inflammation such as Crohn's 
disease or ulcerative colitis within 12 months prior to sub-study registration. 
 
p. 
Patients must not have known prior or suspected hypersensitivity to monoclonal 
antibodies (Grade ≥3).  


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q. 
Patients must not have any history of anaphylaxis or uncontrolled asthma. 
 
Uncontrolled asthma is defined as a patient having any one of the following criteria:  
1. 
Poor symptom control: ACQ consistently >1.5 or ACT <20 (or “not well 
controlled” by NAEPP or GINA guidelines over the 3 months or 
evaluation).  
 
2. 
Frequent severe exacerbations: 2 or more bursts of systemic CSs (>3 
days each) in the previous year.  
 
3. 
Serious exacerbations: at least one hospitalization, Intensive Care Unit 
stay or mechanical ventilation in the previous year.  
 
4. 
Airflow limitation: FEV1<80% predicted (in the presence of reduced 
FEV1/FVC defined as less than the normal lower limit) following a withhold 
of both short- and long-acting bronchodilators. 
r. 
Patients must not have experienced any immune related adverse event ( including 
but not limited to pneumonitis), that led to permanent discontinuation of prior 
immunotherapy and/or required prolonged high dose of steroids (defined as>10mg 
daily prednisone or equivalent for more than 56 days (8 weeks)). 
 
s. 
Patients must not have evidence of active infection requiring systemic therapy. 
 
t. 
Patients must not have received any live attenuated vaccinations within 28 days 
prior to sub-study registration. 
 
u. 
Patients must have an ANC ≥ 1,500/mcl, platelet count ≥ 100,000 mcl, and 
hemoglobin ≥ 9 g/dL obtained within 28 days prior to sub-study registration. 
Patients must be transfusion independent (i.e., no blood product transfusions for 
a period of at least 14 days prior to sub-study registration). 
 
5.4 
Specimen Submission Criteria 
 
a. 
Patients must agree to have blood specimens submitted for circulating tumor DNA 
(ctDNA) as outlined in Section 15.3. 
 
b. 
Patients must also be offered participation in banking and in the correlative studies 
for collection and future use of specimens as described in Section 15.4. 
 
5.5 
Regulatory Criteria 
 
a. 
Patients must be informed of the investigational nature of this study and must sign 
and give written informed consent in accordance with institutional and federal 
guidelines. 
 
b. 
As a part of the OPEN registration process (LUNGMAP Section 13.2 for OPEN 
access instructions) the treating institution's identity is provided in order to ensure 
that the current (within 365 days) date of institutional review board approval for this 
study has been entered in the system. 
 
c. 
Patients with impaired decision-making capacity are eligible as long as their 
neurological or psychological condition does not preclude their safe participation 
in the study (e.g., tracking pill consumption and reporting adverse events to the 


S1900C 
 
 
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investigator). For patients with impaired decision making capabilities, legally 
authorized representatives may sign and give informed consent on behalf of study 
patient in accordance with applicable federal, local, and CIRB regulations. 
 
 
6.0 
STRATIFICATION FACTORS 
 
There are no stratification factors in this study. 
 
 
7.0 
TREATMENT PLAN 
 
For treatment or dose modification questions, please contact Dr. Ferdinandos Skoulidis and Dr. 
Jennifer Marie Suga at S1900CMedicalQuery@swog.org. For dosing principles or questions, 
please consult the SWOG Policy #38 "Dosing Principles for Patients on Clinical Trials" at 
https://www.swog.org/sites/default/files/docs/2017-11/Policy38.pdf. 
 
7.1 
Precautions 
See Section 3.0 and Appendix 18.5 for drug interactions and precautions.  
Patients must not receive any live attenuated vaccinations during protocol treatment.  
7.2  
Pre-Medication and Supportive Care 
 
a. 
Pre-medication associated with standard drug administration and supportive care 
(including anti-diarrheas, antibiotics, diuretics or other medications) may be given 
as indicated by the current American Society of Clinical Oncology (ASCO) 
guidelines. 
 
b. 
In order to mitigate infusion-related reactions, a premedication with an 
antihistamine and with acetaminophen 30 to 60 minutes prior to the first 4 infusions 
of avelumab is mandatory (for example, 25-50 mg diphenhydramine and 500-650 
mg acetaminophen IV or oral). Premedication should be administered for 
subsequent 
avelumab 
infusions 
based 
upon 
clinical 
judgment 
and 
presence/severity of prior infusion reactions. This may be modified based on local 
treatment standards and guidelines, as appropriate.  
 
c. 
Small volume, low dose palliative radiotherapy (≤ 20 Gy) for painful bone 
metastases is permitted, provided that no target lesions are encompassed, and 
the patient does not have progression as defined in Section 10.0. Delaying the 
next dose of protocol therapy by up to two weeks is permitted. 
 
7.3 
Disease Assessment 
 
See Section 9.0 for disease assessment timepoints. Submit scans as outlined in Section 
14.0 and Section 15.0. 
 
Disease Assessment During Treatment 
CT or MRI (the same method used at pre-study to meet the eligibility criteria in Section 5.3) 
must be performed on week 6 (± 7 day window), week 12 (± 7 day window), and then every 
8 weeks (± 7 day window) thereafter regardless of treatment delays, until discontinuation 
of protocol treatment. The 6 weeks should start from sub-study registration. If the patient 
remains on protocol treatment after progression due to clinical benefit in the opinion of the 
treating investigator (per Section 7.6), scans must continue per protocol schedule until 
treatment is discontinued.  


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Pre-study Brain CT/MRI is required per Section 5.3. If patient has brain metastases at 
baseline, scans must use the same modality as baseline and be repeated at week 12 (± 7 
days) and every 8 weeks (± 7 days) thereafter while on treatment. 
 
Disease Assessment During Off Protocol Treatment, Prior to Progression 
After off protocol treatment prior to progression, disease assessments should continue 
every 12 weeks (± 7 day window) until progression. 
 
If patient has brain metastases at baseline, continue brain CT or MRI scans (same modality 
as baseline) after off protocol treatment prior to progression, as clinically indicated. For 
alignment with the protocol and good clinical practice, recommended frequency of brain 
scans after off protocol treatment (and prior to progression) is at least every 12 weeks, 
unless more frequent scans are clinically appropriate. 
7.4 
Treatment – S1900C 
 
Agent 
Dose 
Route 
Schedule * 
 
 
Talazoparib 
1000 mcg 
PO 
Daily  
 
            
 
Avelumab 
800 mg 
IV over 
Days 1 & 15 
 
 
60 mins 
 
 
 
 
 
 
*  Note:  One cycle = 28 calendar days 
 
Setting: Avelumab should be administered in a setting that allows for access to and 
administration of therapy for anaphylaxis, such as the ability to implement immediate 
resuscitation measures.  Steroids, epinephrine (1:1,000 dilution), allergy medications (IV 
antihistamines), bronchodilators, or equivalents, and oxygen should be available for 
immediate access. Sites must have a plan to contact emergency services to provide 
prompt advanced life support including intubation. 
Observation period:  Following avelumab infusions, patients must be observed for 30 
minutes post-infusion for potential infusion-related reactions.   
Patient Instructions: 
Patients should be advised that talazoparib is a toxic substance and that patients and their 
caregivers should always use gloves when handling capsules.  
 
Patients should be instructed to swallow talazoparib capsules whole and not to chew them 
prior to swallowing. Talazoparib can be taken with or without food. No capsule should be 
ingested if it is broken, cracked, or otherwise not intact. Patients should be encouraged to 
take their dose at approximately the same time each day (preferably in the morning).  
 
Patients who miss a day’s dose entirely must be instructed NOT to “make it up” the next 
day.  
If more than 12 hours has elapsed from usual dose time (e.g. 10am), patient should 
consider that day skipped, and he/she should resume treatment the next day at the usual 
time. 
 
Patients who vomit any time after taking a dose must be instructed NOT to “make it up,” 
and to resume treatment the next day as prescribed.  


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Patients who inadvertently take one extra dose during a day must be instructed to skip the 
next day’s dose. 
Note: On days the patient is in-clinic, there are no study dosing order of study drugs.  
 
7.5 
Drug Compliance Documentation 
 
Drug compliance will be recorded by patients in the Patient Diary (see Appendix 18.4). 
Institutional CRAs will review and ascertain patient adherence with protocol therapy at the 
end of treatment for each cycle.  The Patient Diary should be kept in the patient's research 
chart. All sites must use the Patient Diary provided. CIRB requires that the provided 
Patient Diary be utilized for this study. 
 
7.6  
Criteria for Removal from Protocol Treatment 
 
a. 
Progression of disease or symptomatic deterioration (as defined in Sections 10.2d 
and 10.2e). However, the patient may continue protocol treatment as long as the 
patient is continuing to clinically benefit from treatment in the opinion of the treating 
investigator. Patients should still be removed from protocol treatment for criteria 
below. 
 
Upon progression, the Request for New Sub-Study Assignment Form may be 
submitted under the patient’s screening protocol (LUNGMAP) to receive a new 
sub-study assignment (see Section 14.4i). 
 
b. 
Unacceptable toxicity.  
 
c. 
Treatment delay for any reason is > 28 days except for patients receiving steroid 
therapy for an immune related adverse event (as noted in Section 8.0). If patient 
is receiving steroid therapy for an immune related adverse event (irAE), the 
maximum dose delay could be 84 days to allow tapering of the steroid dose to ≤ 
10 mg prednisone or equivalent. 
 
d. 
The patients may withdraw from protocol treatment at any time for any reason. 
 
7.7  
Discontinuation of Treatment 
 
All reasons for discontinuation of treatment must be documented in the Off Protocol 
Treatment Notice. 
 
7.8 
Follow-Up Period 
 
All patients will be followed until death or 3 years after sub-study registration, whichever 
occurs first. 
 
Note: Patients who enroll on a new sub-study following progression must continue follow-
up on this sub-study, in addition to follow-up on the new sub-study. 
 
 
8.0 
TOXICITIES TO BE MONITORED AND DOSE MODIFICATIONS 
 
8.1 
NCI Common Terminology Criteria for Adverse Events 
 
This study will utilize the CTCAE (NCI Common Terminology Criteria for Adverse Events) 
Version 5.0 for toxicity and Serious Adverse Event reporting.  A copy of the CTCAE Version 


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5.0 can be downloaded from the CTEP home page (http://ctep.cancer.gov).  All appropriate 
treatment areas should have access to a copy of the CTCAE Version 5.0. 
 
8.2 
General Considerations 
 
a. 
Missed doses are to be omitted rather than made up. 
 
b. 
If multiple toxicities are experienced, dose modifications will be based on the 
toxicity requiring the largest dose reduction. 
 
c. 
Once talazoparib dose is reduced, patients will continue at the new dose. No 
talazoparib dose re-escalations are allowed. 
 
d. 
A maximum of three dose reductions are allowed. 
 
e. 
The maximum dose delay for any reason is 28 days, with the exception that if 
patient is receiving steroid therapy for an immune related adverse event (irAE), the 
maximum dose delay could be 84 days to allow tapering of the steroid dose to ≤ 
10 mg prednisone or equivalent. 
 
f. 
The assessment for discontinuation of talazoparib should be made separately from 
the assessment made for discontinuation of avelumab.  
 
g. 
Although there is overlap among the discontinuation criteria, if discontinuation 
criteria are met for avelumab but not for talazoparib, treatment with talazoparib 
may continue if avelumab is discontinued, at the discretion of the treating 
physician. In the event that criteria are met subsequently for resumption of 
avelumab while treatment with talazoparib is ongoing, avelumab should be re-
introduced on the first day of the next scheduled cycle of therapy. The above 
criteria would also apply if discontinuation criteria are met for talazoparib but not 
for avelumab. 
 
If a patient receiving combination therapy meets criteria for discontinuation and the 
investigator is unable to determine whether the event is related to both or one study 
drug, the patient should discontinue both drugs. 
 
See Section 7.4 for patient instructions. 
 
8.3 
Dose Interruptions – Avelumab 
 
Dose modifications should be made based on the observed toxicity, as summarized in the 
tables below.  
 
a. 
Treatment Modification for Symptoms of Infusion-Related Reactions 
 


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NCI-CTCAE Grade  
Treatment Modification for Avelumab 
Grade 1 – mild 
Mild transient reaction; infusion interruption not indicated; 
intervention not indicated. 
Decrease avelumab infusion rate by 50% 
and monitor closely for any worsening. 
 
Grade 2 – moderate 
Therapy or infusion interruption indicated but responds 
promptly to symptomatic treatment (for example, 
antihistamines, NSAIDs, narcotics, IV fluids); 
prophylactic medications indicated for  24 h. 
Temporarily discontinue avelumab infusion. 
Resume infusion at 50% of previous rate 
once infusion-related reaction has resolved 
or decreased to at least Grade 1 in severity 
and monitor closely for any worsening. 
Grade 3 or Grade 4 – severe or life-threatening 
Grade 3: Prolonged (for example, not rapidly responsive 
to symptomatic medication and/or brief interruption of 
infusion); recurrence of symptoms following initial 
improvement; hospitalization indicated for clinical 
sequelae. 
Grade 4: Life-threatening consequences; urgent 
intervention indicated. 
Stop avelumab infusion immediately and 
disconnect infusion tubing from the patient. 
Patients must be withdrawn immediately 
from avelumab treatment and must not 
receive any further avelumab treatment. 
- If avelumab infusion rate has been decreased by 50% or interrupted due to an infusion reaction, it 
must remain decreased for the next scheduled infusion.  If no infusion reaction is observed in the next 
scheduled infusion, the infusion rate may be returned to baseline at the subsequent infusions based 
on investigator’s medical judgment. 
- If hypersensitivity reaction occurs, the patient must be treated according to the best available medical 
practice.  
IV = intravenous; NCI-CTCAE = National Cancer Institute-Common Terminology Criteria for Adverse 
Event; NSAIDs = nonsteroidal anti-inflammatory drugs. 
 
 
 


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b. 
Management of Immune-mediated Adverse Reactions 
 
Gastrointestinal irAEs 
Severity of 
Diarrhea/Colitis 
Initial Management 
Follow-up Management 
Grade 1 
  
Continue avelumab therapy 
Symptomatic treatment (e.g. loperamide) 
Close monitoring for worsening 
symptoms 
Educate patient to report worsening 
immediately 
If worsens: 
Treat as Grade 2, 3 or 4.  
Grade 2  
  
Withhold avelumab therapy 
Symptomatic treatment 
If improves to Grade ≤ 1:  
Resume avelumab therapy 
 
If persists > 5-7 days or recurs: 
Treat as Grade 3 or 4. 
Grade 3 to 4 
 
Withhold avelumab for Grade 3. 
Permanently discontinue avelumab for 
Grade 4 or recurrent Grade 3. 
 
1 to 2 mg/kg/day prednisone IV or 
equivalent 
Add prophylactic antibiotics for opportunistic 
infections  
Consider lower endoscopy  
If improves:  
Continue steroids until Grade ≤ 1, then 
taper < 10 mg per day over at least 1 
month; resume avelumab therapy 
following steroids taper (for initial Grade 
3). ** 
 
If worsens, persists > 3 to 5 days, or 
recurs after improvement: 
Add infliximab 5mg/kg (if no 
contraindication). Note: infliximab 
should not be used in cases of 
perforation or sepsis.  
 
Permanently discontinue avelumab for 
Grade 4 diarrhea or colitis or recurrent 
Grade 3 diarrhea or colitis 


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Dermatological irAEs 
Grade of Rash 
Initial Management 
Follow-up Management 
Grade 1 to 2  
 
Continue avelumab therapy Symptomatic 
therapy (for example, antihistamines, topical 
steroids)  
If persists > 1 to 2 weeks or recurs:  
Withhold avelumab therapy  
Consider skin biopsy  
 
Consider 0.5-1.0 mg/kg/day prednisone 
or equivalent. Once improving, taper 
steroids < 10 mg per day over at least 1 
month, consider prophylactic antibiotics 
for opportunistic infections, and resume 
avelumab therapy following steroids 
taper. ** 
If worsens:  
Treat as Grade 3 to 4.  
Grade 3 to 4 
 
Withhold avelumab for Grade 3. 
Permanently discontinue for Grade 4 or 
recurrent Grade 3.  
Consider skin biopsy  
Dermatology consult  
1 to 2 mg/kg/day prednisone or equivalent 
Add prophylactic antibiotics for opportunistic 
infections  
If improves to Grade ≤ 1:  
Taper steroids < 10 mg per day over at 
least 1 month; resume avelumab 
therapy following steroids taper (for 
initial Grade 3). ** 
Pulmonary irAEs 
Grade of 
Pneumonitis 
Initial Management 
Follow-up Management 
Grade 1 
Radiographic 
changes only  
Consider withholding avelumab therapy  
Monitor for symptoms every 2 to 3 days  
Consider Pulmonary and Infectious Disease 
consults  
Clinically re-assess at least every 2 
weeks and resume at the discretion of 
the treating investigator 
If worsens:  
Treat as Grade 2 or Grade 3 to 4.  
Grade 2 
 
Withhold avelumab therapy 
Pulmonary and Infectious Disease consults 
Monitor symptoms daily; consider 
hospitalization  
1 to 2 mg/kg/day prednisone or equivalent 
Add prophylactic antibiotics for opportunistic 
infections  
Consider bronchoscopy, lung biopsy  
Re-assess every 1 to 3 days  
If improves:  
When symptoms return to Grade ≤ 1, 
taper steroids < 10 mg per day over at 
least 1 month, and then resume 
avelumab therapy following steroids 
taper ** 
If not improving after 2 weeks or 
worsening:  
Treat as Grade 3 to 4.  


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Grade 3 to 4 
  
Permanently discontinue avelumab therapy. 
Hospitalize. 
Pulmonary and Infectious Disease consults. 
1 to 2 mg/kg/day prednisone or equivalent  
Add prophylactic antibiotics for opportunistic 
infections  
Consider bronchoscopy, lung biopsy  
If improves to Grade ≤ 1:  
Taper steroids < 10 mg per day over at 
least 1 month ** 
If not improving after 48 hours or 
worsening:  
Add additional immunosuppression (for 
example, infliximab, cyclophosphamide, 
IV immunoglobulin, or mycophenolate 
mofetil)  
Hepatic irAEs 
Grade of Liver 
Test Elevation 
Initial Management 
Follow-up Management 
Grade 1 
 
Continue avelumab therapy 
Continue liver function monitoring  
If worsens:  
Treat as Grade 2 or 3 to 4.  
Grade 2 
 
Withhold avelumab therapy 
Increase frequency of monitoring to every 3 
days. 
 
Administer corticosteroids (initial dose of 1 
to 2 mg/kg/day prednisone or equivalent, 
followed by a corticosteroid taper) for Grade 
2 or greater hepatitis. 
If returns to Grade ≤ 1: 
Resume routine monitoring; resume 
avelumab therapy after corticosteroid 
taper. ** 
If elevation persists > 5 to 7 days or 
worsens:  
Treat as Grade 3 to 4. 
Grade 3 to 4 
 
Permanently discontinue avelumab therapy  
Increase frequency of monitoring to every 1 
to 2 days  
1 to 2 mg/kg/day prednisone or equivalent 
Add prophylactic antibiotics for opportunistic 
infections  
Consult gastroenterologist/ hepatologist 
Consider obtaining MRI/CT scan of liver and 
liver biopsy if clinically warranted  
If returns to Grade ≤ 1:  
Taper steroids < 10 mg per day over at 
least 1 month ** 
If does not improve in > 3 to 5 days, 
worsens or rebounds:  
Add mycophenolate mofetil 1 gram (g) 
twice daily  
If no response within an additional 3 to 
5 days, consider other 
immunosuppressants per local 
guidelines. 
Renal irAEs 
Grade of 
Creatinine 
Increased  
Initial Management 
Follow-up Management 
Grade 1 
 
Continue avelumab therapy 
Continue renal function monitoring 
If worsens: 
Treat as Grade 2 to 3 or 4. 


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Grade 2 to 3 
 
 
 
 
 
Withhold avelumab therapy 
Increase frequency of monitoring to every 3 days 
1 to 2 mg/kg/day prednisone or equivalent. 
Add prophylactic antibiotics for opportunistic 
infections 
Consider renal biopsy 
If returns to Grade ≤1: 
Taper steroids < 10 mg per day 
over at least 1 month, and resume 
avelumab therapy following 
steroids taper. ** 
If worsens:  
Treat as Grade 4. 
Grade 4 
 
 
 
 
 
 
 
Permanently discontinue avelumab therapy 
Monitor creatinine daily 
1 to 2 mg/kg/day prednisone or equivalent. 
Add prophylactic antibiotics for opportunistic 
infections 
Consider renal biopsy 
Nephrology consult 
If returns to Grade ≤1: 
Taper steroids < 10 mg per day 
over at least 1 month. ** 
Cardiac irAEs 
Myocarditis 
Initial Management 
Follow-up Management 
New onset of cardiac signs or 
symptoms and / or new 
laboratory cardiac biomarker 
elevations (e.g. troponin, CK-MB, 
BNP) or cardiac imaging 
abnormalities suggestive of 
myocarditis.  
Withhold avelumab therapy. 
Hospitalize. 
In the presence of life-threatening 
cardiac decompensation, consider 
transfer to a facility experienced in 
advanced heart failure and 
arrhythmia management. 
Cardiology consult to establish 
etiology and rule-out immune-
mediated myocarditis.  
Guideline based supportive 
treatment as per cardiology 
consult.* 
 
Consider myocardial biopsy if 
recommended per cardiology 
consult. 
If symptoms improve and 
immune-mediated etiology is 
ruled out, re-start avelumab 
therapy. 
 
If symptoms do not 
improve/worsen, viral 
myocarditis is excluded, and 
immune-mediated etiology is 
suspected or confirmed 
following cardiology consult, 
manage as immune-mediated 
myocarditis. 
Immune-mediated myocarditis 
Permanently discontinue avelumab. 
Guideline based supportive 
treatment as appropriate as per 
cardiology consult.* 
1 to 2 mg/kg/day prednisone or 
equivalent 
Once improving, taper steroids 
< 10 mg per day over at least 1 
month. ** 
 
If no improvement or 
worsening, consider additional 


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Add prophylactic antibiotics for 
opportunistic infections. 
immunosuppressants (e.g. 
azathioprine, cyclosporine A). 
*Local guidelines, or eg. ESC or AHA guidelines  
ESC guidelines website:  https://www.escardio.org/Guidelines/Clinical-Practice-Guidelines 
AHA guidelines website: 
http://professional.heart.org/professional/GuidelinesStatements/searchresults.jsp?q=&y=&t=1001 
Endocrine irAEs 
Endocrine Disorder 
Initial Management 
Follow-up Management 
Grade 1 or Grade 2 
endocrinopathies 
(hypothyroidism, 
hyperthyroidism, adrenal 
insufficiency, type I diabetes 
mellitus) 
Continue avelumab therapy 
Endocrinology consult if needed 
 
Start thyroid hormone 
replacement therapy (for 
hypothyroidism), anti-thyroid 
treatment (for hyperthyroidism), 
corticosteroids (for adrenal 
insufficiency) or insulin (for Type I 
diabetes mellitus) as appropriate.   
 
Rule-out secondary 
endocrinopathies (i.e. 
hypopituitarism / hypophysitis) 
Continue hormone 
replacement/suppression and 
monitoring of endocrine 
function as appropriate. 
Grade 3 or Grade 4 
endocrinopathies 
(hypothyroidism, 
hyperthyroidism, adrenal 
insufficiency, type I diabetes 
mellitus) 
Withhold avelumab therapy 
Consider hospitalization 
Endocrinology consult 
 
Start thyroid hormone 
replacement therapy (for 
hypothyroidism), anti-thyroid 
treatment (for hyperthyroidism), 
corticosteroids (for adrenal 
insufficiency) or insulin (for type I 
diabetes mellitus) as appropriate.   
 
Rule-out secondary 
endocrinopathies (i.e. 
hypopituitarism / hypophysitis) 
Resume avelumab once 
symptoms and/or laboratory 
tests improve to Grade ≤ 1 (with 
or without hormone 
replacement/suppression). 
 
Continue hormone 
replacement/suppression and 
monitoring of endocrine 
function as appropriate.  
Hypopituitarism/Hypophysitis 
(secondary endocrinopathies) 
If secondary thyroid and/or 
adrenal insufficiency is confirmed 
(i.e. subnormal serum FT4 with 
inappropriately low TSH and/or 
low serum cortisol with 
inappropriately low ACTH): 
Resume avelumab once 
symptoms and hormone tests 
improve to Grade ≤ 1 (with or 
without hormone replacement). 
 
In addition, for hypophysitis with 
abnormal MRI, resume 
avelumab only once shrinkage 
of the pituitary gland on MRI/CT 
scan is documented.  


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• 
Refer to endocrinologist for 
dynamic testing as indicated 
and measurement of other 
hormones (FSH, LH, GH/IGF-
1, PRL, testosterone in men, 
estrogens in women)  
• 
Hormone 
replacement/suppressive 
therapy as appropriate  
• 
Perform pituitary MRI and 
visual field examination as 
indicated 
 
If hypophysitis confirmed: 
• 
Continue avelumab if mild 
symptoms with normal MRI. 
Repeat the MRI in 1 month 
• 
Withhold avelumab if 
moderate, severe or life-
threatening symptoms of 
hypophysitis and/or abnormal 
MRI. Consider hospitalization. 
Initiate corticosteroids (1 to 2 
mg/kg/day prednisone or 
equivalent) followed by 
corticosteroids taper during at 
least 1 month. ** 
• 
Add prophylactic antibiotics 
for opportunistic infections. 
 
Continue hormone 
replacement/suppression 
therapy as appropriate. 
Other irAEs (not described above) 
Grade of other irAEs  
Initial Management 
Follow-up Management 
Stevens Johnson Syndrome 
(SJS)/toxic epidermal necrolysis 
(TEN), rhabdomyolysis, 
myasthenia gravis, histiocytic 
necrotizing lymphadenitis, 
demyelination, vasculitis, 
hemolytic anemia, hypophysitis, 
iritis, and encephalitis)  
 
 
Permanently discontinue 
avelumab. 
Grade 2 or Grade 3 clinical signs 
or symptoms suggestive of a 
potential irAE 
Withhold avelumab therapy 
pending clinical investigation 
If irAE is ruled out, manage as 
appropriate according to the 
diagnosis and consider re-
starting avelumab therapy 
If irAE is confirmed, treat as 
Grade 2 or 3 irAE. 
Grade 2 irAE or first 
occurrence of Grade 3 irAE 
Withhold avelumab therapy 
1 to 2 mg/kg/day prednisone or 
equivalent   
If improves to Grade ≤ 1:  


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Add prophylactic antibiotics for 
opportunistic infections  
Specialty consult as appropriate 
Taper steroids < 10 mg per day 
over at least 1 month and 
resume avelumab therapy 
following steroids taper. ** 
Recurrence of same Grade 3 
irAEs 
Permanently discontinue 
avelumab therapy 
1 to 2 mg/kg/day 
prednisone or equivalent 
Add prophylactic antibiotics for 
opportunistic infections  
Specialty consult as appropriate 
If improves to Grade ≤ 1:  
Taper steroids < 10 mg per day 
over at least 1 month. ** 
Grade 4  
 
Permanently discontinue 
avelumab therapy 
1 to 2 mg/kg/day 
prednisone or equivalent and/or 
other immunosuppressant as 
needed 
Add prophylactic antibiotics for 
opportunistic infections  
Specialty consult. 
If improves to Grade ≤ 1:  
Taper steroids < 10 mg per day 
over at least 1 month ** 
** Requirement for 10 mg per 
day or greater prednisone or 
equivalent for more than 12 
weeks for reasons other than 
hormonal replacement for 
adrenal insufficiency 
 
Persistent Grade 2 or 3 irAE 
lasting 12 weeks or longer 
Permanently discontinue 
avelumab therapy 
Specialty consult 
 
Abbreviations: ACTH=adrenocorticotropic hormone; ADL=activities of daily living; ALT=alanine aminotransferase; 
AST=aspartate aminotransferase; BNP=B-type natriuretic peptide; CK-MB=creatine kinase MB;  CT= computed 
tomography; FSH=follicle-stimulating hormone; GH=growth hormone; IGF-1=insulin-like growth factor 1; 
irAE=immune-related adverse event; IV=intravenous; LH=luteinizing hormone; MRI=magnetic resonance imaging; 
NCI-CTCAE=National 
Cancer 
Institute-Common 
Terminology 
Criteria 
for 
Adverse 
Events; 
PRL=prolactin;T4=thyroxine; TSH=thyroid-stimulating hormone; ULN=upper limit of normal. 
 
8.4 
Dose Modifications – Talazoparib  
 
Dose modifications should be made based on the observed toxicity, as summarized in the 
tables below. For any grade 4 toxicity, please contact Dr. Ferdinandos Skoulidis and Dr. 
Jennifer Marie Suga at S1900CMedicalQuery@swog.org.  
 
DRUG 
DOSE LEVEL 
DOSE 
 
Talazoparib 
Full 
 
1000 mcg/day 
 
-1 Level 
 
750 mcg/day 
 
-2 Level 
 
500 mcg/day 
 
-3 Level 
250 mcg/day 
 
-4 Level 
Discontinue 
 
 
 


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Table 1: Renal Impairment Dose Modifications 
Toxicity  
Dose Modification 
Grade ≥ 3 
Hold protocol treatment until resolution to < Grade 2, treatment may 
then resume at the next lower dose 
 
 
Table 2: Dose Modifications Based on Hematologic or Nonhematologic Toxicity 
Note: No dose modifications are required for any grade lymphopenia. 
Toxicity  
Dose Modification 
Hemoglobin Grade ≥ 3   
Hold protocol treatment until resolution to < Grade 2, treatment 
may then resume at the next lower dose.  
 
Platelet count Grade ≥ 3   
Hold protocol treatment until resolution to ˂ Grade 2, treatment 
may then resume at the next lower dose.  
 
Neutrophil count Grade ≥ 3   
Hold protocol treatment until resolution to ˂ Grade 2, treatment 
may then resume at the next lower dose.  
 
 
 
Table 3: Liver Test Abnormalities That Require Dose Modifications 
Baseline AST or 
ALT Value 
Elevation 
Dose Modification and Toxicity Management 
≤ 3 × ULN 
> 5 × ULN to ≤ 8 × 
ULN  
Hold protocol treatment pending investigation into alternative 
causes of drug-induced liver injury (DILI). The patient should be 
followed for possible DILI. Resuming treatment, at one dose level 
reduction if no prior dose reduction otherwise resume at same dose, 
may be considered if an alternative cause for the impaired liver tests 
(i.e., ALT, AST, total bilirubin) is discovered and the laboratory 
abnormalities resolve to < Grade 1. 
The decision to resume treatment should be discussed and agreed 
on unanimously by the patient, treating investigator, and Study 
Chair. Following rechallenge, patients should be closely monitored 
for signs and symptoms of hepatitis, and/or abnormal liver test 
results. If signs or symptoms recur with rechallenge, talazoparib 
should be permanently discontinued and removed from protocol 
treatment.  
 
If an alternative cause for the impaired liver tests cannot be found, 
permanently discontinue and remove from protocol treatment. 
See Table 4 for evaluations.  
> 3 to ≤ 5 × ULN 
> 8 × ULN  
Baseline Total 
Bilirubin Value 
Elevation 
≤ 1.5 × ULN 
> 3 × ULN 
 
Talazoparib should be discontinued permanently if ALL of the following 4 criteria are met 
(i.e., potential severe DILI/Hy’s Law case):  
 
1. 
AST or ALT increases to ≥ 3 × ULN (> 5 × ULN if baseline ALT/AST is > 3 and 
≤ 5 × ULN) 
 
2. 
Total bilirubin increases to > 2 × ULN and/or INR > 1.5 
 
3. 
Alkaline phosphatase (ALP) value does not reach 2 × ULN 
 


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4. 
No alternative cause explains the combination of the above laboratory 
abnormalities; important alternative causes include, but are not limited to: 
• 
Hepatobiliary tract disease 
• 
Viral 
hepatitis 
(e.g., 
hepatitis 
A/B/C/D/E, 
Epstein-Barr 
virus, 
cytomegalovirus, 
herpes 
simplex 
virus, 
varicella, 
toxoplasmosis, 
parvovirus) 
• 
Congestive heart failure, hypotension, or any cause of hypoxia to the liver 
causing ischemia 
• 
Exposure to hepatotoxic agents/drugs or hepatotoxins, including herbal 
and dietary supplements, plants, and mushrooms   
• 
Alcoholic hepatitis 
• 
Non-alcoholic steatohepatitis (NASH)  
• 
Autoimmune hepatitis  
• 
Wilson’s disease and hemochromatosis 
• 
Alpha-one antitrypsin deficiency  
 
If an alternative cause for hepatotoxicity is identified or if the liver test abnormalities 
do not reach the specified severity, it is recommended, but not required that 
talazoparib be withheld or permanently discontinued, as appropriate for the safety 
of the patient based on the patient population and/or severity of the hepatotoxicity 
or event.   
 
All patients in whom talazoparib is withheld (either conditionally or permanently) 
due to a potential DILI are to undergo a period of “close observation” until the liver 
test abnormalities return to baseline or normal values.  The evaluations listed in 
Table 4 are recommend, but not required to be performed. 
 
Table 4: Liver Monitoring After Events Meeting Hy’s Law Criteria or 
Suggesting Potentially Severe Drug-Induced Liver Injuries 
 
Results 
Frequency for Repeating Liver (AST, ALT, Bilirubin 
[Total and Direct]) and INR Tests  
After the initial liver test abnormality  
Within 24 hours  
If AST or ALT ≥ 3 × ULN (> 5 × ULN if baseline 
ALT/AST is > 3 and ≤ 5 × ULN), and total bilirubin > 
2 × ULN or INR > 1.5 
Every 24 hours until laboratory abnormalities improve 
If ALT or AST ≥ 3 × ULN (> 5 × ULN if baseline 
ALT/AST is > 3 and ≤ 5 × ULN) and total bilirubin 
and/or INR are normal  
Every 48 to 72 hours until laboratory abnormalities 
improve 
If the liver test abnormalities improve AND the patient 
is asymptomatic 
Frequency may decrease 
 
As DILI is a diagnosis of exclusion, it is important to initiate investigation of 
alternative causes for abnormal liver tests; this may include consultation with a 
hepatologist.  The Study Chair should be contacted for questions regarding 
adequate follow-up tests. 
 
 


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8.5 
Dose Modification Contacts 
 
For treatment or dose modification questions, please contact Dr. Ferdinandos Skoulidis 
and Dr. Jennifer Marie Suga at S1900CMedicalQuery@swog.org. For dosing principles or 
questions, please consult the SWOG Policy #38 "Dosing Principles for Patients on Clinical 
Trials" at https://www.swog.org/sites/default/files/docs/2017-11/Policy38.pdf. 
 
8.6 
Adverse Event Reporting Requirements 
 
TheRave® Cancer Therapy Evaluation Program Adverse Event Reporting System (CTEP-
AERS) integration enables evaluation of post-baseline Adverse Events (AE) entered in 
Rave to determine whether they require expedited reporting and facilitates entry in CTEP-
AERS for those AEs requiring expedited reporting. 
 
All AEs that occur after baseline are collected in Medidata Rave using the Adverse Event 
form, which is available for entry at each treatment or reporting period, and used to collect 
AEs that start during the period or persist from the previous reporting period. CRA will enter 
AEs that occur prior to the start of treatment on a baseline form that is not included in the 
Rave-CTEP-AERS integration. AEs that occur prior to enrollment must begin and end on 
the baseline Adverse Events form and should not be included on the standard Adverse 
Events form that is available at treatment unless there has been an increase in grade. 
 
Prior to sending AEs through the rule’s evaluation process, site staff should verify the 
following on the Adverse Event form in Rave: 
• 
The reporting period (course/cycle) is correct; and 
• 
AEs are recorded and complete (no missing fields) and the form is query free.  
 
The CRA reports AEs in Rave at the time the Investigator learns of the event. If the CRA 
modifies an AE, it must be re-submitted for rules evaluation. 
 
Upon completion of AE entry in Medidata Rave, the CRA submits the AE for rules 
evaluation by completing the Expedited Reporting Evaluation form. Both NCI and protocol-
specific reporting rules evaluate the AEs submitted for expedited reporting. A report is 
initiated in CTEP-AERS using information entered in Medidata Rave for AEs that meet 
reporting requirements. The CRA completes the report by accessing CTEP-AERS via a 
direct link on the Medidata Rave Expedited Reporting Evaluation form. 
 
In the rare occurrence, that Internet connectivity is lost; a 24-hour notification is to be made 
to CTEP by telephone at 301-897-7497. Once internet connectivity is restored, the 24-hour 
notification that was phoned in must be entered immediately into CTEP-AERS using the 
direct link from Medidata Rave. 
 
Additional information about the CTEP-AERS integration is available on the CTSU website: 
• 
Study specific documents: Protocols > Documents> Education and Promotion; and   
• 
Expedited Safety Reporting Rules Evaluation user guide: Resources > CTSU 
Operations Information> User Guides & Help Topics. 
NCI requirements for SAE reporting are available on the CTEP website:  
• 
NCI Guidelines for Investigators: Adverse Event Reporting Requirements is 
available 
at 
https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/aeguid
elines.pdf. 
 
If you have questions about this process, please contact the SAE Program Manager 210-
614-8808 or email  adr@swog.org. 


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The CTEP-AERS electronic reporting system “Help” feature has detailed instructions in the 
section "Submitting Reports for RAVE Users". 
 
8.7 
Serious Adverse Event Reporting Requirements 
 
a. 
Definition and Purpose 
 
Definition:  Adverse event means any untoward medical occurrence associated 
with the use of a drug in humans, whether or not considered drug related. (FDA, 
21 CFR 312.32). See Table 8.6 for definition of a Serious Adverse Event (SAE) 
and reporting requirements. 
 
Adverse event data collection and reporting, which are required as part of every 
clinical trial, are done to ensure the safety of patients enrolled in the studies as well 
as those who will enroll in future studies using similar agents. Adverse events are 
reported in a routine manner at scheduled times during a trial. (Directions for 
routine reporting are provided in Section 14.0.) Additionally, certain adverse events 
must be reported in an expedited manner to allow for more timely monitoring of 
patient safety and care. The following guidelines prescribe expedited adverse 
event reporting for this protocol.  
 
b. 
Reporting Method 
 
This study requires that expedited adverse events be reported to SWOG 
Operations Office using the Cancer Therapy Evaluation Program Adverse Event 
Reporting System (CTEP-AERS).  CTEP’s guidelines for CTEP-AERS can be 
found at http://ctep.cancer.gov.   
 
NOTE:  For this study, all adverse events requiring expedited reporting must 
initially be reported on the Adverse Event Form in the appropriate Treatment 
Cycle folder in Medidata Rave.  The CTEP-AERS report must then be initiated 
directly from the Adverse Event Form in Medidata Rave.  Do not initiate the 
CTEP-AERS report via the CTEP-AERS website. 
 
c. 
When to report an event in an expedited manner 
 
Some adverse events require 24-hour notification (refer to Table 8.6) via CTEP-
AERS.  
 
In the rare event when internet connectivity is disrupted a 24-hour notification is 
made to SWOG by telephone at 210-614-8808 or by email adr@swog.org.  An 
electronic report MUST be submitted immediately upon re-establishment of 
internet connection. 
 
When the adverse event requires expedited reporting, submit the report via CTEP-
ARS within the number of calendar days of learning of the event specified in Table 
8.6 
 
d. 
Other recipients of adverse event reports 
 
The SWOG Operations Office will forward reports and documentation to the 
appropriate regulatory agencies and drug companies as required. 
 
Adverse events determined to be reportable to the Institutional Review Board 
responsible for oversight of the patient must be reported according to local policy 
and procedures. 


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e. 
Expedited reporting for investigational agents 
 
Expedited reporting is required if the participant has received at least one dose of 
the investigational agent(s) as part of the trial. Reporting requirements are 
provided in Table 8.6. The investigational agent(s) used in this study are avelumab 
and talazoparib. If there is any question about the reportability of an adverse event 
or if Internet connectivity is disrupted please telephone or email the SAE Program 
Manager at the Operations Office, 210/614-8808 or adr@swog.org, before 
preparing the report. 
 
NOTE: For this study, all adverse events requiring expedited reporting must 
initially be reported on the Adverse Event Form in the appropriated 
Treatment Cycle folder in Medidata Rave.  Once the adverse event is entered 
into RAVE, the Rules Engine will confirm whether or not the adverse event 
requires expedited reporting.  The CTEP-AERS report must then be initiated 
directly from the Adverse Event Form in Medidata Rave.  Do not initiate the 
CTEP-AERS report via the CTEP-AERS website.  Sites are encouraged to 
confirm the Expedited Reporting Evaluation Recommendation with the 
reporting criteria outlined in Table 8.6 (Section 8.6f.2). 
 
 


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Table 8.6: 
Late Phase 2 and Phase 3 Studies:  Expedited Reporting Requirements for Adverse Events that 
Occur on Studies under a Non-CTEP IND within 30 Days of the Last Administration of the 
Investigational Agent/Intervention Talazoparib + Avelumab1  
 
FDA REPORTING REQUIREMENTS FOR SERIOUS ADVERSE EVENTS (21 CFR Part 312) 
NOTE:  Investigators MUST immediately report to the sponsor (NCI) ANY Serious Adverse Events, whether or not 
they are considered related to the investigational agent(s)/intervention (21 CFR 312.64) 
 
 An adverse event is considered serious if it results in ANY of the following outcomes:   
1) 
Death 
2) 
A life-threatening adverse event  
3) 
An adverse event that results in inpatient hospitalization or prolongation of existing hospitalization for ≥ 24 
hours  
4) 
A persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions  
5) 
A congenital anomaly/birth defect.  
6) 
Important Medical Events (IME) that may not result in death, be life threatening, or require hospitalization 
may be considered serious when, based upon medical judgment, they may jeopardize the patient or 
subject and may require medical or surgical intervention to prevent one of the outcomes listed in this 
definition. (FDA, 21 CFR 312.32; ICH E2A and ICH E6). 
 
ALL SERIOUS adverse events that meet the above criteria MUST be immediately reported to the NCI via CTEP-
AERS within the timeframes detailed in the table below. 
Hospitalization 
Grade 1 
Timeframes 
Grade 2 
Timeframes 
Grade 3 Timeframes 
Grade 4 & 5 
Timeframes 
Resulting in 
Hospitalization  
≥ 24 hrs 
10 Calendar Days 
24-Hour 5 
Calendar Days 
Not resulting in 
Hospitalization  
≥ 24 hrs 
Not required 
10 Calendar Days 
NOTE:  Protocol specific exceptions to expedited reporting of serious adverse events are found in Section 8.6f. 
Expedited AE reporting timelines are defined as: 
o “24-Hour; 5 Calendar Days” - The AE must initially be reported via CTEP-AERS within 24 hours of 
learning of the AE, followed by a complete expedited report within 5 calendar days of the initial 24-
hour report. 
 
o “10 Calendar Days” - A complete expedited report on the AE must be submitted within 10 calendar 
days of learning of the AE. 
1Serious adverse events that occur more than 30 days after the last administration of investigational 
agent/intervention and have an attribution of possible, probable, or definite require reporting as follows:  
 
Expedited 24-hour notification followed by complete report within 5 calendar days for: 
• All Grade 4, and Grade 5 AEs 
Expedited 10 calendar day reports for: 
• Grade 2 adverse events resulting in hospitalization or prolongation of hospitalization  
• Grade 3 adverse events 
May 5, 2011 
 
 


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f. 
Additional Instructions or Exceptions to CTEP-AERS Expedited Reporting 
Requirements for Late Phase 2 and Phase 3 Studies Utilizing an Agent 
under a Non-CTEP IND: 
 
1. 
Group-specific instructions. 
 
Supporting Documentation Submission – Within 5 calendar days submit 
documentation supporting the CTEP-AERS report to the SWOG 
Operations Office by fax 210-614-0006. Specific instructions will be sent 
by email to the reporting site by the SAE Program Manager. 
 
2.  
The adverse events listed below also require expedited reporting via 
CTEP-AERS for this trial: 
• 
≥ Grade 2 AST or ALT if after evaluation it meets Hy’s Law 
https://www.fda.gov/downloads/Drugs/.../guidances/UCM174090.pdf  
(See Sections IV.C, Case Report Forms and IV.E4, Assessment of 
Hy’s Law Cases in the Clinical Trials Database) 
• 
≥ Grade 2 bilirubin 
 
g. Reporting Secondary Malignancy, including AML/ALL/MDS 
 
1.   
A secondary malignancy is a cancer caused by treatment for a previous 
malignancy (e.g., treatment with investigational agent/intervention, 
radiation or chemotherapy).  A secondary malignancy is not considered a 
metastasis of the initial neoplasm. 
 
 
SWOG requires all secondary malignancies that occur following treatment 
with an agent under a Non-NCI IND to be reported via CTEP-AERS.  Three 
options are available to describe the event. 
 
• 
Leukemia secondary to oncology chemotherapy (e.g., Acute 
Myelocytic Leukemia [AML]) 
 
• 
Myelodysplastic syndrome (MDS) 
 
• 
Treatment-related secondary malignancy 
 
 
Any malignancy possibly related to cancer treatment (including AML/MDS) 
should also be reported via the routine reporting mechanisms outlined in 
each protocol. 
 
Second Malignancy: A second malignancy is one unrelated to the 
treatment of a prior malignancy (and is NOT a metastasis from the 
initial malignancy).  Second malignancies require ONLY routine 
reporting.  
 
For more information see: 
http://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/
aeguidelines.pdf  
 
2. 
Supporting documentation should be submitted to CTEP in accordance 
with instructions provided by the CTEP-AERS system.  Supporting 
documentation must also be submitted to SWOG Operations Office by fax 
to 210-614-0006. 
              
NOTE: If a patient has been enrolled in more than one NCI-sponsored study, the 
report must be submitted for the most recent trial. 


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h.  
Reporting Pregnancy, Pregnancy Loss, and Death Neonatal 
 
1. 
Pregnancy Study participants who become pregnant while on study; that 
pregnancy should be reported in an expedited manner via CTEP-AERS 
as Grade 3 “Pregnancy, puerperium and perinatal conditions – Other 
(pregnancy)” under the Pregnancy, puerperium and perinatal 
conditions SOC.   
 
Additionally, the pregnancy outcome for patients on study should be 
reported via CTEP-AERS at the time the outcome becomes known, 
accompanied by the same Pregnancy Report Form used for the initial 
report. 
 
2. 
Pregnancy Loss  Pregnancy loss is defined in CTCAE as “Death in 
utero.” Pregnancy loss should be reported expeditiously as Grade 4 
“Pregnancy loss” under the Pregnancy, puerperium and perinatal 
conditions SOC.   
 
A Pregnancy loss should NOT be reported as a Grade 5 event under the 
Pregnancy, puerperium and perinatal conditions SOC, as currently CTEP-
AERS recognizes this event as a patient death. 
 
3. 
Death Neonatal  “Death neonatal is defined in CTCAE as “Newborn death 
occurring during the first 28 days after birth.”    A neonatal death should 
be reported expeditiously as Grade 4 “Death neonatal” under the 
General disorders and administration SOC. 
 
Neonatal death should NOT be reported as a Grade 5 event under the 
General disorders and administration SOC as currently CTEP-AERS 
recognizes this event as a patient death. 
 
NOTE:  When submitting CTEP-AERS reports for “Pregnancy, “Pregnancy loss”, 
or “Neonatal loss”, the Pregnancy Information Form should also be completed and 
faxed with any additional medical information to 210-614-0006.  The potential risk 
of exposure of the fetus to the investigational agent(s) or chemotherapy agent(s) 
should be documented in the “Description of Event” section of the CTEP-AERS 
report. 
 
The 
Pregnancy 
Information 
Form 
is 
available 
at:  
http://ctep.cancer.gov/protocolDevelopment/adverse_effects.htm .   
 


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9.0 
STUDY CALENDAR 
 
9.1 
Talazoparib and Avelumab 
 
NOTE: The study calendar is a good tool for a general snapshot of study requirements but does not replace details provided in the 
relevant sections of the protocol. Use the study calendar in conjunction with the detailed procedures and information in the protocol 
but not as the sole or primary source for managing this trial. 
 
  
Pre-Reg 
(w/in 28 days 
prior to 
registration, 
unless 
otherwise 
noted) 
Cycle Length = 28 days 
(+/- 3 days) 
At Off 
Tx 
Off Tx FU Prior 
to Prog 
Off Tx FU After 
Prog 2  
REQUIRED 
STUDIES 
Cycle 1 
Cycle 2 
Cycle 3 
Subsequent Cycles 1 
PHYSICAL 
  
History & Physical 
Exam 
X 
X 
X 
X 
X 
X 
X 3 
  
Weight & 
Performance Status 
X 
X 
X 
X 
X 
X 
X 3 
  
Patient Diary 5 
  
X 
X 
X 
X 
X  
  
  
Toxicity Notation 
  
X 
X 
X 
X 
X 
X 6 
X 6 
Smoking Status 
Assessment 
X 
  
  
  
  
  
X 
  
  
  
LABORATORY 
  
  
  
  
  
  
  
If labs obtained w/in 14 days 
prior to tx, tests need not be 
repeated on C1D1. 
Results up to 48 hours prior to Day 1 tx 
  
  
  
CBC/Diff/Platelets/ 
Hgb 
X 
X 
X 
X 
X 
X 
X 6 
X 6 
Chemistry Panel 7 
X 
X 
X 
X 
X 
X 
X 6 
X 6 
 
TSH w/ Reflex to 
Free T4 
X 13 
 
X 13 
 
X 13  
(every other cycle) 
 
X 6 
X 6 
 
Hepatitis B/ C viral 
load test  
X 14 
 
 
 
 
 
 
 
 


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Pre-Reg 
(w/in 28 days 
prior to 
registration, 
unless 
otherwise 
noted) 
Cycle Length = 28 days 
(+/- 3 days) 
At Off 
Tx 
Off Tx FU Prior 
to Prog 
Off Tx FU After 
Prog 2  
REQUIRED 
STUDIES 
Cycle 1 
Cycle 2 
Cycle 3 
Subsequent Cycles 1 
 
HIV viral load test  
X 14  
 
 
 
 
 
 
 
 
X-RAYS & SCANS 
CT or MRI for 
Disease 
Assessment 4 
X 4 
  
X 4 
Week 6 
X 4 
Week 12 
 X 4 
 
  
X 4  
  
Brain CT/MRI 
X 8 
  
  
X 8 
Week 12 
 X 8 
 
  
X 8 
  
SPECIMEN SUBMISSION 
ctDNA Whole Blood 
 
 X 10 
(pre-tx) 
  
 X 10  
  
  
 
X 10 
(first progression & off protocol treatment) 
Buffy Coat /Plasma 
for Banking 11 
X 
  
X 11 
X 11 
 
X 11 
(cycle 4 only) 
X 11 
(first progression) 
TREATMENT        
  
(28-day cycle) 
Talazoparib 12 
  
X 
Days 1-28 
X 
Days 1-28 
X 
Days 1-28 
X 
Days 1-28 
  
  
  
 
Avelumab 12 
 
X 
Days 1, 15 
X 
Days 1, 15 
X 
Days 1, 15 
X 
Days 1, 15 
 
 
 
 
NOTE: 
Forms are found on the CTSU website (www.ctsu.org).  Forms submission guidelines are found in Section 14.0. 


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NOTE: 
Unless indicated otherwise in the protocol, scheduled procedures and assessments (treatment administration, toxicity assessment for continuous 
treatment, disease assessment, specimen collection and follow-up activities) must follow the established SWOG guidelines on the allowed 
protocol visits/treatment window as outlined in https://www.swog.org/clinical-trials/protocol-workbench. SWOG Best Practices allows for a +/- 3 
day window for 28-day cycles. 
Footnotes for Calendar 9.1 (Talazoparib and Avelumab): 
1 
During continued treatment, items marked under physical and laboratory should be performed prior to every subsequent cycle, unless otherwise 
noted. Disease assessments and image submission are to take place on weeks 6 and 12 (± 7 days), and then every 8 weeks (± 7 days) 
thereafter, regardless of treatment delay. Treatment and evaluation will continue until any one of the criteria in Section 7.6 is met. If the patient 
remains on protocol treatment after progression due to clinical benefit in the opinion of the treating investigator (per Section 7.6), treatment 
schedule must continue per protocol. 
2 
After off protocol treatment after progression, follow-up will occur (with lab tests and scans performed at the discretion of the treating physician) 
every 6 months for 2 years then at end of 3 years from date of sub-study registration. Note: Patients who enroll on a new sub-study following 
progression must continue follow-up on this sub-study, in addition to follow-up on the new sub-study. 
3 
After off protocol treatment prior to progression, patients should be followed by repeating indicated studies every 8 weeks or more often as 
clinically indicated until progression. Disease assessment should continue per Section 7.3. 
4 
CT or MRI (the same method used at pre-study to meet the eligibility criteria in Section 5.3) must take place on weeks 6 and 12 (± 7 days), and 
then every 8 weeks (± 7 days) thereafter, regardless of treatment delay, while on treatment. After off protocol treatment prior to progression, 
scans must take place every 12 weeks (± 7 days) until disease progression. The 6 weeks should start from sub-study registration. See Sections 
5.3 and 7.3 for additional details.  
5 
The CRA will review the Patient Diary at the end of each cycle (see Appendix 18.4). 
6 
Assessments should continue if clinically indicated and until resolution of all acute adverse events. 
7 
Chemistry panel (non-fasting) must include creatinine, LFTs (ALT, AST), and bilirubin. 
8 
Brain CT/MRI is required per Sections 5.3 and 7.3. If patient has brain metastases at baseline, scans must use the same modality as baseline 
and be performed at week 12 (+/- 7 days) and every 8 weeks thereafter while on treatment. After off treatment prior to progression, patients 
should be followed by repeating brain CT or MRI every 12 weeks as clinically indicated until progression. 
10 
See Section 15.3. Note: Kits must be ordered and will take up to 3 days to arrive. 
11 
With patient’s consent additional research blood draws will be collected per Section 15.4. 
12 
See Section 7.0 for treatment details.  
13 
TSH and if abnormal, reflex to Free T4 and other work up per investigator, should be performed as clinically indicated at pre-study. While on 
treatment, monitor thyroid function every other cycle. See Section 8.4 for avelumab dose modifications. 
14 
See Section 5.1 for details. 


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10.0 
CRITERIA FOR EVALUATION AND ENDPOINT ANALYSIS 
 
10.1 
Measurability of Lesions 
 
a. 
Measurable disease: Measurable disease is defined differently for lymph nodes 
compared with other disease and will be addressed in a separate section below. 
 
1. 
Lesions that can be accurately measured in at least one dimension 
(longest diameter to be recorded) as ≥ 2.0 cm by chest x-ray, by ≥ 1.0 cm 
with CT or MRI scans, or ≥ 1.0 cm with calipers by clinical exam. All tumor 
measurements must be recorded in decimal fractions of centimeters (or 
millimeters). 
 
The defined measurability of lesions on CT scan is based on the 
assumption that CT slice thickness is 0.5 cm or less. It is strongly 
recommended that CT slice of 0.5 cm be used.  If CT scans have slice 
thickness greater than 0.5 cm, the minimum size for a measurable lesion 
should be twice the slice thickness.   
 
2. 
Malignant lymph nodes are to be considered pathologically enlarged and 
measurable if it measures ≥ 1.5 cm in SHORT AXIS (greatest diameter 
perpendicular to the long axis of the lymph node) when assessed by scan 
(CT scan slice recommended being no greater than 0.5 cm). 
 
b. 
Non-measurable disease:  All other lesions (or sites of disease), including small 
lesions (longest diameter < 1.0 cm or pathologic lymph nodes with ≥ 1.0 cm to < 
1.5 cm short axis), are considered non-measurable disease. Bone lesions, 
leptomeningeal disease, ascites, pleural/pericardial effusions, lymphangitis 
cutis/pulmonitis, inflammatory breast disease, and abdominal masses (not 
followed by CT or MRI), are considered as non-measurable as are previously 
radiated lesions that have not progressed. 
 
c. 
Notes on measurability 
 
1. 
For CT and MRIs, the same type of scanner should be used and the image 
acquisition protocol should be followed as closely as possible to prior 
scans. It is no longer necessary to distinguish between spiral and 
conventional CT. 
 
2. 
Body scans should be performed with breath-hold scanning techniques, if 
possible.  
 
3. 
PET-CT: At present, the low dose or attenuation correction CT portion of 
a PET-CT is not always of optimal diagnostic CT quality for use with 
RECIST measurements. However, if the site can document that the CT 
performed as part of a PET-CT is of identical diagnostic quality to a 
diagnostic CT, then the CT portion of the PET-CT can be used for RECIST 
measurements and can be used interchangeably with stand-alone CT. 
The slice thickness of 0.5 cm or less is highly recommended. If CT scans 
have slice thickness > 0.5 cm, the minimum size for a measurable lesion 
should be twice the slice thickness. 
 
4. 
Ultrasound: Ultrasound is not useful in assessment of lesion size and 
should not be used as a method of measurement. 
 


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5. 
Cystic lesions that meet the criteria for radiographically defined simple 
cysts should not be considered as malignant lesions (neither measurable 
nor non-measurable) since they are, by definition simple cysts. 
 
6. 
If a target lesion becomes very small some radiologists indicate that it is 
too small to measure. If the lesion is actually still present, a default 
measurement of 0.5 cm should be applied. If the radiologist believes the 
lesion has gone, a default measurement of 0.0 cm should be recorded. 
 
10.2 
Objective Status at Each Disease Evaluation 
 
Objective Status is to be recorded at each evaluation. All measurable lesions up to a 
maximum of 2 lesions per organ, 5 lesions in total, representative of all involved organs, 
should be identified as target lesions at baseline. All other lesions (or sites of disease) 
including any measurable lesions over and above the 5 target lesions should be identified 
as non-target lesions. Measurements must be provided for target measurable lesions, 
while presence or absence must be noted for non-target measurable and non-measurable 
disease.  
 
For studies that use disease progression as an endpoint, all potential sites of metastases 
should be evaluated at each time point rather than following only sites of disease identified 
at baseline. It is acceptable to image only the areas of the body most likely to be involved 
with metastatic disease for the tumor type (chest, abdomen, pelvis, and/or bone scan are 
typical), with the addition of any areas with suspected involvement based upon clinical 
symptoms.  For study-specific imaging requirements, see the Study Calendar in Section 
9.0. 
 
a. 
Complete Response (CR): Complete disappearance of all target and non-target 
lesions (with the exception of lymph nodes mentioned below). No new lesions. No 
disease related symptoms.  Any lymph nodes (whether target or non-target) must 
have reduction in short axis to < 1.0 cm. All disease must be assessed using the 
same technique as baseline. 
 
b. 
Partial Response (PR): Applies only to patients with at least one measurable 
lesion. Greater than or equal to 30% decrease under baseline of the sum of 
appropriate diameters of all target measurable lesions. No unequivocal 
progression of non-measurable disease. No new lesions. All target measurable 
lesions must be assessed using the same techniques as baseline. 
 
c. 
Stable: Does not qualify for CR, PR, Progression or Symptomatic Deterioration. 
All target measurable lesions must be assessed using the same techniques as 
baseline. 
 
d. 
Progression: One or more of the following must occur: 20% increase in the sum 
of appropriate diameters of target measurable lesions over smallest sum observed 
(over baseline if no decrease during therapy) using the same techniques as 
baseline, as well as an absolute increase of at least 0.5 cm. Unequivocal 
progression of non-measurable disease in the opinion of the treating physician (an 
explanation must be provided).  Appearance of any new lesion/site. Death due to 
disease without prior documentation of progression and without symptomatic 
deterioration (see 10.2e). 
 
Notes on progression and new lesions:  
1. 
For equivocal findings of progression (e.g. very small and uncertain new 
lesions; cystic changes or necrosis in existing lesions), treatment may 
continue until the next scheduled assessment.  If at the next scheduled 


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assessment, progression is confirmed, the date of progression should be 
the earlier date when progression was suspected. 
 
2. 
FDG-PET imaging can complement regular scans in identifying new 
lesions according to the following algorithm.  
o 
Negative FDG-PET at baseline, with a positive FDG-PET at 
follow-up is a sign of progression based on a new lesion. 
o 
No FDG-PET at baseline and a positive FDG-PET at follow-up 
corresponding to a potential new site of disease must have a 
confirmation by anatomical assessment (e.g. CT, MRI, x-ray) as 
new site of disease to be considered progressive disease. In such 
a case, the date of progressive disease will be the date of the initial 
abnormal FDG-PET.   
 
3. 
A previous abnormal target lymph node that became normal and 
subsequently enlarged in size meeting the criteria for a pathologic and 
measurable lymph node (a short axis of ≥ 1.5 cm) should be added to the 
sum of diameters to determine if criteria for progression are met based on 
target lesions. 
 
4. 
A previously abnormal non-target lymph node that became normal and 
subsequently recurred must meet the criteria for progression based on 
non-target lesions to be considered progression. 
 
A normal lymph node at baseline (<1.0 cm) that subsequently becomes pathologic 
is considered a new lesion and should be considered progression. 
 
If a single pathologic lymph node is driving the progression event, continuation of 
treatment/follow-up and confirmation by a subsequent exam should be 
contemplated. If it becomes clear that the new lymph node has not 
resolved, or has increased in size, the date of progression would be the 
date the new lymph node was first documented. 
 
e. 
Symptomatic deterioration: Global deterioration of health status requiring 
discontinuation of treatment without objective evidence of progression. Efforts 
should be made to obtain objective evidence of progression after discontinuation. 
 
f. 
Assessment inadequate, objective status unknown: Progression or 
symptomatic deterioration has not been documented, and one or more target 
measurable lesions have not been assessed or inconsistent assessment methods 
were used. 
Objective status notes: 
1. 
Non-measurable and non-target measurable disease do not affect 
Objective Status in determination of CR (must be absent--a patient who 
otherwise has a CR, but who has non-measurable or non-target 
measurable disease present or not assessed, will be classified as having 
a PR). However, non-measurable and non-target lesions are included in 
determination of progression (if new sites of disease develop or if 
unequivocal progression occurs in the opinion of the treating physician).  
2. 
An objective status of PR or stable cannot follow one of CR. Stable can 
follow PR only in the rare case that tumor increases too little to qualify as 
progression, but enough that a previously documented 30% decrease no 
longer holds. 
3. 
In cases for which initial flare reaction is possible (hypercalcemia, 
increased bone pain, erythema of skin lesions), objective status is not 


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progression unless either symptoms persist beyond 4 weeks or there is 
additional evidence of progression. 
4. 
Lesions that appear to increase in size due to presence of necrotic tissue 
will not be considered to have progressed.  
5. 
For bone disease documented on bone scan only, increased uptake does 
not constitute unequivocal progression. However, increase in the soft 
tissue component of a lesion as measured by CT or MRI would constitute 
progression. 
6. 
Appearance of new pleural effusions does not constitute unequivocal 
progression unless cytologically proven of neoplastic origin, since some 
effusions are a toxicity related to therapy or other medical conditions. 
Increase in the size of an existing effusion does not constitute unequivocal 
progression, since the fluid status of the patient could alter the size of the 
effusion.  
7. 
If CR determination depends on a lesion for which the status is unclear by 
the required tests, it is recommended the residual lesion be investigated 
with biopsy or fine needle aspirate.  
8. 
Lymph nodes are considered one organ.  Only two lymph nodes should 
be selected as target lesions.  Other involved lymph nodes should be 
assessed and followed as non-target lesions. 
9. 
“Paired” organs, i.e. lungs, kidneys and ovaries, are considered one organ.   
10. 
Pleural-based lung lesions are considered part of the lung in determining 
target lesions (a maximum of two lung lesions should be selected), 
whereas pleural effusions/thickening can be reported as a separate site. 
 
10.3 
Best Response 
 
This is calculated from the sequence of objective statuses. 
 
a. 
CR:  Two or more objective statuses of CR a minimum of four weeks apart 
documented before progression or symptomatic deterioration. 
 
b. 
PR:  Two or more objective statuses of PR or better a minimum of four weeks apart 
documented before progression or symptomatic deterioration, but not qualifying as 
CR. 
 
c. 
Unconfirmed CR:  One objective status of CR documented before progression or 
symptomatic deterioration but not qualifying as CR or PR. 
 
d. 
Unconfirmed PR:  One objective status of PR documented before progression or 
symptomatic deterioration but not qualifying as CR, PR or unconfirmed CR. 
 
e. 
Stable/no response:  At least one objective status of stable/no response 
documented at least 6 weeks after registration and before progression or 
symptomatic deterioration, but not qualifying as anything else above. 
 
f. 
Increasing disease:  Objective status of progression within 12 weeks of 
registration, not qualifying as anything else above. 
 
g. 
Symptomatic deterioration: Objective status of symptomatic deterioration within 
12 weeks of registration, not qualifying as anything else above.   
 
h. 
Inadequate assessment, response unknown:  Progression or symptomatic 
deterioration greater than 12 weeks after registration and no other response 
category applies. 
 
10.4 
Performance Status 


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Patients will be graded according to the Zubrod Performance Status Scale. 
 
POINT 
DESCRIPTION 
 
0 
Fully active, able to carry on all pre-disease performance without 
restriction. 
 
1 
Restricted in physically strenuous activity but ambulatory and able 
to carry out work of a light or sedentary nature, e.g., light 
housework, office work. 
 
2 
Ambulatory and capable of self-care but unable to carry out any 
work activities; up and about more than 50% of waking hours. 
 
3 
Capable of limited self-care, confined to bed or chair more than 
50% of waking hours. 
 
4 
Completely disabled; cannot carry on any self-care; totally 
confined to bed or chair. 
 
10.5 
Time to Death 
 
From date of sub-study registration to date of death due to any cause.  Patients last known 
to be alive are censored at date of last contact. 
 
10.6 
Investigator-Assessed Progression-Free Survival 
 
From date of sub-study registration to date of first documentation of progression assessed 
by local review or symptomatic deterioration (as defined above), or death due to any cause.  
Patients last known to be alive without report of progression are censored at date of last 
disease assessment. For patients with a missing scan (or consecutive missing scans) 
whose subsequent scan determines progression, the expected date of the first missing 
scan (as defined by the disease assessment schedule) will be used as the date of 
progression.  
 
10.7 
Progression-Free Survival by Central Review 
 
From date of sub-study registration to date of first documentation of progression assessed 
by central review or symptomatic deterioration (as defined above), or death due to any 
cause.  Patients last known to be alive without report of progression are censored at date 
of last disease assessment. For patients with a missing scan (or consecutive missing 
scans) whose subsequent scan determines progression, the expected date of the first 
missing scan (as defined by the disease assessment schedule) will be used as the date of 
progression.  
 
10.8 
Duration of Response (DoR) 
 
From date of first documentation of response (CR or PR) to date of first documentation of 
progression assessed by local review or symptomatic deterioration (as defined above), or 
death due to any cause among patients who achieve a response (CR or PR).  Patients last 
known to be alive without report of progression are censored at date of last disease 
assessment. For patients with a missing scan (or consecutive missing scans) whose 
subsequent scan determines progression, the expected date of the first missing scan (as 
defined by the disease assessment schedule) will be used as the date of progression. 
 
10.9 
Disease Control Rate at 12 Weeks (DCR12) 


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Disease control at 12 weeks is defined as a best response of CR, PR, UPR, or UCR by/at 
the second disease assessment at 12 weeks after registration (+/- 2 weeks), or stable 
disease at 12 weeks after registration (+/- 2 weeks).  Patients with missing or delayed 
disease assessment at 12 weeks (+/- 2 weeks), at or before the disease assessment at 20 
weeks (+/- 2 weeks) with documented lack of progression (CR, PR, UPR, UCR, or stable) 
are coded as having disease control at 12 weeks.  Patients not known to have disease 
control at 12 weeks who have at least 12 weeks of follow-up will be coded as not having 
disease control at 12 weeks. 
 
 
11.0 
STATISTICAL CONSIDERATIONS 
 
11.1 
Sample Size with Power Justification 
 
The co-primary objectives of the study are to evaluate the best objective response (CR, 
UCR, PR, UPR per 10.3) rate (ORR) and the disease control (CR, UCR, PR, UPR, or SD 
per 10.3) rate at 12 weeks after registration (DCR12) in patients treated with avelumab and 
talazoparib.  
 
Eligibility is based on detection of pathogenic STK11 genomic alterations (non-
synonymous somatic mutations in STK11 or bi-allelic loss on tumor genomic profiling using 
the  FoundationOne assay – see Section 5.1). 
 
The total accrual goal to the study is 40 eligible and evaluable patients. An interim analysis 
will take place on the first 20 eligible patients enrolled are evaluable for response (see 
details in section 11.2). Assuming that 10% of patients who are enrolled will be not eligible, 
the total accrual goal is 44 patients.    
 
The sample size is based on a design with 90% power and 1-sided 0.05 level type I error 
to rule out an objective response rate (ORR) of 10% or less if the true ORR is 28% or 
greater and 90% power to rule out a DCR12 of 30% at the 5% level, if the true rate is 54%.  
However, the rules for concluding activity are based on a combination of these thresholds 
(see Table 2 for details).  
 
The following table (Table 1) describes the power to conclude there is activity based on 
the underlying true response and stable disease rates by 12 weeks after registration 
(recalling that disease control is the combined response and stable disease rates).  The 
properties of this design are summarized in Table 2.  
 
Table 1: Probability of concluding activity of talazoparib and avelumab  
True 
Response 
Rate 
Power 
for RR 
alone* 
True Disease Control Rate 
30% 
35% 
45% 
55% 
10% 
4 
6 
11 
31 
47 
15% 
23 
25 
29 
51 
73 
20% 
56 
56 
56 
68 
87 
25% 
81 
81 
81 
84 
94 
30% 
94 
94 
94 
94 
98 
* Provided for comparison if the study success rules did not include DCR and were based 
on RR alone 
 
The expected prevalence of the STK11 biomarker is 17%. Sites are notified of a patient’s 
sub-study assignment by the SWOG Statistical and Data Management Center (SDMC) 
after the results of the biomarker testing have been reported to the SDMC. As described in 


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LUNGMAP Section 11.0 (the Lung-MAP screening protocol), patients with biomarkers 
matching only this study will be assigned to this study and sub-study assignment will be 
based on randomization for patients eligible for multiple biomarker-driven sub-studies. The 
frequency of patients assigned to this sub-study will depend on the other biomarker-driven 
sub-studies actively accruing while this study is accruing and could be less than the 
percentages eligible for the sub-studies.  
 
The expected average monthly accrual rate is 3 patients per month. The anticipated 
duration of accrual is 15-19 months, depending on the need for a temporary closure. The 
anticipated duration of follow-up to the final analysis is 6 months after the study is closed 
to accrual. 
 
11.2 
Analysis Plan 
 
The interim analysis will take place when the first 20 enrolled eligible patients are evaluable 
for response. Patients will be considered evaluable if they receive at least one dose each 
of talazoparib and avelumab and satisfy one of the following: 1) had a response reported, 
2) have gone off protocol treatment in the absence of response, or 3) have submitted at 
minimum the first 4 disease assessments indicating lack of response. Patients not known 
to have a response will be coded as non-responders. Accrual will be placed on a temporary 
hold if all patients in the interim analysis set have submitted data for second scheduled 
disease assessment and the rule to continue accrual has not be met.  
 
The rule for continuing past the 1st stage is based on an assessment of objective response 
alone. The observation of 2 or more objective responses (CR or PR, confirmed or 
unconfirmed) in the would be considered sufficient evidence to continue accrual up to a 
total of 40 eligible patients who received at least one dose of talazoparib and avelumab. 
 
Table 2. Likelihood of continuing to 2nd stage 
True 
Probability 
of 
response 
Probability of 
continuing  
5% 
25% 
10% 
61% 
15% 
82% 
20% 
93% 
25% 
98% 
30% 
99% 
 
If the study meets the criteria to continue to full accrual: 
• 
the observation of at least 8 patients with a response (20% response rate) would 
be considered evidence to rule out a response rate of 10%.   
• 
the observation of at least 18 patients with disease control at 12 weeks (45% or 
greater) would be considered evidence to rule out a DCR12 of 30%.   
 
The thresholds for interpretation of activity is based on these thresholds but allows for 
interpretation of activity based on a minimal level of responses and the disease control rate 
threshold. The study would be considered to have provided sufficient evidence to study 
talazoparib and avelumab further if the criteria in the following table are met: 
 
 


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Table 3: Criteria for interpretation of study data at final analysis 
   
 
 
 
 
 
 
 
Secondary objectives will include an assessment of the frequency and severity of toxicities, 
estimation of the distribution of progression-free survival (PFS), overall survival (OS), and 
duration of response among responders.  
 
Binary proportions and associated confidence intervals will be calculated.  The method of 
Kaplan-Meier will be used to estimate survival distributions and the Brookmeyer-Crowley 
method will be used to estimate confidence intervals around medians.   
 
With 40 eligible patients, binary proportions (response rates, DCR12, PFS and OS at 
landmark times) can be estimated to be within 16% with 95% confidence.  
 
 
12.0 
DISCIPLINE REVIEW 
 
12.1 
Radiology Review 
 
Central collection is required but review of scans will not be triggered if the study will not 
be submitted to the FDA for FDA approval of the investigational therapy. Central review of 
scans will be triggered only if deemed necessary for FDA evaluation.  A detailed description 
of the central radiology PFS review, including image acquisition parameters and image 
submission instructions, can be found in LUNGMAP Section 18.2f. 
 
a. 
To ensure the highest standards and consistency between different centers, all 
scans for disease assessment (baseline, interim and end of treatment scans) must 
be submitted to the National Cancer Institute’s National Clinical Trials Network 
(NCTN) Imaging and RT Quality Assurance Service Core (IROC) in Ohio for 
centralized review (Section 15.5). 
 
b. 
Centralized review will be performed by 3 radiology experts. The scans will be 
submitted to IROC.  IROC will transmit the scans to the reviewers who will transmit 
the results to the SWOG Statistics and Data Management Center. 
 
c. 
Details of submission of scans to IROC for centralized review and on the central 
review process are listed in Section 15.5 and LUNGMAP Appendix 18.2f. 
 
 
13.0 
REGISTRATION GUIDELINES 
 
See Section 13.0 of LUNGMAP for registration guidelines. 
 
In order to open Lung-MAP studies at the site, a separate Study Specific Worksheet (SSW) is 
required to be submitted to the CIRB for the LUNGMAP screening protocol and each sub-study.  
 
13.1 
Registration Timing 
 
Initiation of treatment must be planned to start no more than 10 calendar days after sub-
study registration.  
Response Evaluation 
Disease Control at 12 weeks evaluation 
# w/ disease control 
# responses 
< 18 w/ DCR12 
≥18 w/ DCR12 
< 4  
No evidence of activity 
No evidence of activity 
4-7 
No evidence of activity 
Evidence of activity 
≥ 8  
Evidence of activity 
Evidence of activity 


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13.2  
Investigator/Site Registration 
 
For investigator/site registration, please refer to Section 13.2 of the LUNGMAP screening 
protocol. In addition, a Delegation Task Log is required for this sub-study.  
 
Delegation of Task Log (DTL): 
Each site must complete a protocol-specific Delegation of Tasks Log (DTL) using the DTL 
application in the Delegation Log section on the CTSU members’ website. The Clinical 
Investigator (CI) is required to review and electronically sign the DTL prior to the site 
receiving an approved site registration status and enrolling patients to the study. To 
maintain an approved site registration status the CI must re-sign the DTL at least annually 
and when a new version of the DTL is released; and activate new task assignments 
requiring CI sign-off. Any individual at the enrolling site on a participating roster may initiate 
the site DTL. Once the DTL is submitted for CI approval, only the designated DTL 
Administrators or the CI may update the DTL. Instructions on completing the DTL are 
available in the Help Topics button in the DTL application and include a Master Task List, 
which describes DTL task assignments, CI signature, and CTEP registration requirements. 
 
 
14.0 
DATA SUBMISSION SCHEDULE 
 
14.1 
Data Submission Requirement 
 
Data must be submitted according to the protocol requirements for ALL patients 
registered, whether or not assigned treatment is administered, including patients 
deemed to be ineligible.  Patients for whom documentation is inadequate to 
determine eligibility will generally be deemed ineligible. 
 
14.2 
Master Forms 
 
Master forms can be found on the protocol page on the CTSU website (www.ctsu.org) and 
(with the exception of the sample consent form and the Registration Worksheet) must be 
submitted on-line via the Web; see Section 14.3 for details. 
 
14.3 
Data Submission Procedures 
 
a. Medidata Rave is a clinical data management system being used for data 
collection for this trial/study. Access to the trial in Rave is controlled through the 
CTEP-IAM system and role assignments.  
 
Requirements to access Rave via iMedidata: 
• 
A valid CTEP-IAM account; and  
• 
Assigned a Rave role on the LPO or PO roster at the enrolling site of: Rave 
CRA, Rave Read Only, Rave CRA (LabAdmin), Rave SLA, or Rave 
Investigator.  
 
Rave role requirements: 
• 
Rave CRA or Rave CRA (Lab Admin) role must have a minimum of an 
Associate Plus (AP) registration type; 
• 
Rave Investigator role must be registered as a Non-Physician Investigator 
(NPIVR) or Investigator (IVR); and 


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• 
Rave Read Only role must have at a minimum an Associates (A) registration 
type. 
 
Refer to https://ctep.cancer.gov/investigatorResources/default.htm for registration 
types and documentation required. 
 
 This study has a Delegation of Tasks Log (DTL). Therefore, those requiring write 
access to Rave must also be assigned the appropriate Rave tasks on the DTL. 
 
Upon initial site registration approval for the study in Regulatory Support System 
(RSS), all persons with Rave roles assigned on the appropriate roster will be sent 
a study invitation e-mail from iMedidata. To accept the invitation, site staff must log 
in to the Select Login (https://login.imedidata.com/selectlogin) using their CTEP-
IAM user name and password and click on the accept link in the upper right-corner 
of the iMedidata page. Site staff will not be able to access the study in Rave until 
all required Medidata and study specific trainings are completed. Trainings will be 
in the form of electronic learnings (eLearnings) and can be accessed by clicking 
on the link in the upper right pane of the iMedidata screen. If an eLearning is 
required and has not yet been taken, the link to the eLearning will appear under 
the study name in iMedidata instead of the Rave EDC link; once the successful 
completion of the eLearning has been recorded, access to the study in Rave will 
be granted, and a Rave EDC link will display under the study name. 
 
Site staff that have not previously activated their iMedidata/Rave account at the 
time of initial site registration approval for the study in RSS will receive a separate 
invitation from iMedidata to activate their account. Account activation instructions 
are located on the CTSU website, in the Data Management section under the Rave 
resource materials (Medidata Account Activation and Study Invitation 
Acceptance). Additional information on iMedidata/Rave is available on the CTSU 
members’ 
website 
in 
the 
Data 
Management 
> 
Rave 
section 
at 
www.ctsu.org/RAVE/ or by contacting the CTSU Help Desk at 1-888/823-5923 or 
by e-mail at ctsucontact@westat.com.  
 
a. 
You may also access Rave® via the SWOG CRA Workbench via the SWOG 
website (www.swog.org).  
 
For difficulties with the CRA Workbench, please email  
technicalquestion@crab.org. 
 
b. 
Institutions participating through the Cancer Trials Support Unit (CTSU) please 
refer to the CTSU Participation Table. 
 
c. 
The Data Quality Portal (DQP) provides a central location for site staff to manage 
unanswered queries and form delinquencies, monitor data quality and timeliness, 
generate reports, and review metrics.  
 
The DQP is located on the CTSU members’ website under Data Management. The 
Rave Home section displays a table providing summary counts of Total 
Delinquencies and Total Queries. DQP Queries, DQP Delinquent Forms and the 
DQP Reports modules are available to access details and reports of unanswered 
queries, delinquent forms, and timeliness reports. Review the DQP modules on a 
regular basis to manage specified queries and delinquent forms. 
 


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The DQP is accessible by site staff that are rostered to a site and have access to 
the CTSU website. Staff that have Rave study access can access the Rave study 
data using a direct link on the DQP. 
To learn more about DQP use and access, click on the Help icon displayed on the 
Rave Home, DQP Queries, and DQP Delinquent Forms modules. 
 
Note: Some Rave protocols may not have delinquent form details or reports 
specified on the DQP. A protocol must have the Calendar functionality 
implemented in Rave by the Lead Protocol Organization (LPO) for delinquent form 
details and reports to be available on the DQP. Site staff should contact the LPO 
Data Manager for their protocol regarding questions about Rave Calendar 
functionality.   
 
14.4 
Data Submission Overview and Timepoints  
 
a. 
WITHIN 15 DAYS OF S1900C REGISTRATION, SUBMIT: 
 
Vital Status Form 
 
S1900C Eligibility Criteria Form 
 
S1900C Onstudy Form 
 
If needed, also submit: 
Radiation Therapy Form 
Brain Metastases Form 
 
 
Smoking Status Assessment Form 
 
Baseline Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at baseline*  
 
If needed, RT summary and/or planning document* 
 
 
 
 
If needed, radiology report from brain CT/MRI* 
 
*(NOTE: Upload reports via the Source Documentation: Baseline form in Rave)  
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from scans 
performed to assess disease at baseline as specified in Section 15.5 
 
b. 
IF PATIENT CONSENTS, SUBMIT SPECIMENS: 
 
Specimens as specified in Section 15.0  
 
c. 
WITHIN 15 DAYS AFTER EACH CYCLE (CYCLE = 28 DAYS) OF TREATMENT, 
SUBMIT: 
 
Vital Status Form 
 
S1900C Treatment Form 
 
S1900C Adverse Event Form* 
 
If needed, Immune-Related Adverse Event Form 


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S1900C Laboratory Values Form  
 
For Cycle 1 only: Submit the S1900C Pre-Treatment Laboratory Values Form. 
 
*For the last cycle of treatment, include all adverse events occurring within 30 days 
after the last treatment. 
 
d. 
WITHIN 15 DAYS AFTER EVERY DISEASE ASSESSMENT (INCLUDING BOTH 
ON TREATMENT AND OFF PROTOCOL TREATMENT PRIOR TO DISEASE 
PROGRESSION (see Section 9.0 for Disease Assessment Schedule), SUBMIT: 
 
Vital Status Form 
 
Follow-Up Tumor Assessment Form (RECIST 1.1) documenting results of 
assessment 
 
Radiology reports from all scans performed to assess disease at follow-up (NOTE: 
Upload reports via the Source Documentation: Follow-up form in Rave) 
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from scans 
performed to assess disease as specified in Section 15.5. 
 
e. 
WITHIN 15 DAYS OF DISCONTINUATION OF TREATMENT, SUBMIT: 
 
Vital Status Form 
 
Off Protocol Treatment Notice documenting reasons for off protocol treatment 
 
Smoking Status Assessment Form 
 
Forms specified in Section 14.4c. 
 
f. 
WITHIN 30 DAYS, ONCE OFF PROTOCOL TREATMENT EVERY 6 MONTHS 
FOR THE FIRST 2 YEARS FROM S1900C REGISTRATION, THEN AT THE END 
OF YEAR 3 FROM SUB-STUDY REGISTRATION SUBMIT: 
 
Vital Status Form 
 
Advanced NSCLC Follow-Up Form 
 
If needed, also submit: 
Radiation Therapy Form 
Brain Metastases Form 
 
Late Adverse Events (if prior to treatment for progression or relapse or a second 
primary, and prior to non-protocol treatment, the patient experiences any severe 
[Grade ≥ 3] adverse event that is possibly, probably, or definitely related to protocol 
treatment, or a Serious Adverse Event [SAE] of any grade/attribution, that has not 
been previously reported). 
 
g. 
WITHIN 15 DAYS OF PROGRESSION/RELAPSE, SUBMIT: 
 
Vital Status Form 
 
Site(s) of Progression or Relapse Form 
 


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Follow-Up Tumor Assessment Form (RECIST 1.1) 
 
Radiology reports from all scans performed to assess disease at follow-up (NOTE: 
Upload reports via the Source Documentation: Follow-up form in Rave) 
 
Submit to IROC via TRIAD for Central Radiology Review:  Images from scans 
performed to assess disease as specified in Section 15.5. 
 
h. 
WITHIN 30 DAYS OF KNOWLEDGE OF DEATH: 
 
Vital Status Form 
 
Submit the Notice of Death documenting death information and S1900C End of 
Study form.  In addition, if the patient was still on protocol treatment, submit 
materials specified in Section 14.4e or if patient was no longer on treatment, submit 
a final Advanced NSCLC Follow-Up Form. 
 
i. 
DATA SUBMISSION FOR PATIENTS WHO HAVE PROGRESSED AND WISH 
TO REGISTER TO A NEW SUB-STUDY: 
 
WITHIN 15 DAYS OF PROGRESSION/RELAPSE: 
 
Submit the Request for New Sub-Study Assignment Form under the patient’s 
screening protocol (LUNGMAP) in Rave®. Continue follow-up on S1900C per 
Section 9.0. See Section 14.0 of the screening protocol for additional data 
submission requirements following request for new sub-study assignment. 
 
j. 
WITHIN 30 DAYS OF MAXIMUM FOLLOW-UP OF 3 YEARS: 
 
Vital Status Form 
 
S1900C End of Study Form 
 
 
15.0 
SPECIAL INSTRUCTIONS 
 
 
15.1 
Specimen Flow Diagram 
 
Please refer to Section 15 of LUNGMAP for the specimen flow diagram for the screening 
protocol.  
 
15.2 
SWOG Specimen Tracking System (STS) 
 
See LUNGMAP Section 15.1 for SWOG Specimen Tracking System (STS) instructions. 
 
15.3  
LUNGMAP ctDNA Assay – Peripheral Whole Blood (REQUIRED FOR PATIENTS) 
 
 
 
Blood specimens will be collected in order to isolate and investigate circulating tumor DNA 
(ctDNA) and blood tumor mutational burden (bTMB) – a form of fragmented DNA released 
into patient peripheral circulation specifically from the tumors. Analysis of ctDNA can reveal 
the presence of tumor-specific mutations and other abnormalities that can serve as 
biomarkers. The information collected will be limited to tumor-specific abnormalities known 
or suspected to play roles in tumor evolution.  Patient germ-line genetic information will not 
be collected. 
 
a. 
Kit Ordering 


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Immediately after identifying a patient for trial and prior to treatment initiation, sites 
must contact Foundation Medicine, Inc. – Blood Samples, Lab #232, to order kits 
as follows: 
 
• 
Call FMI Client Services at 1-888/988-3639 or email request to 
lung.MAP@FoundationMedicine.com  
• 
Site must identify itself as a participant in the SWOG Lung-MAP S1900C sub-
study and request the “Lung-MAP ctDNA Clinical Trial Kit” 
• 
Reference the FMI Study ID: FoundationOneLiquidDx-AMC-
PRO-20-1496 
• 
Provide the following information: 
o 
Treating physician's name 
o 
Treating physician's email address 
o 
Contact name 
o 
Contact email address 
o 
Contact phone 
o 
Address to which kits should be sent 
o 
Number of kits needed (one per patient per timepoint) 
 
Kits will arrive within 3 days after ordering (excluding weekends and holidays). 
 
Kits will read “Foundation Medicine Clinical Trials Kit,” and include two Roche Cell-
Free DNA blood collection tubes, collection instructions, FedEx return bags, and 
pre-printed FedEx airway bills. Blood collection tubes must be used before their 
expiration date. 
 
b. 
Timepoints 
 
Collect blood at: 
• 
After sub-study registration and prior to treatment initiation 
o 
Recommended to collect on Cycle 1 Day 1 (prior to treatment) 
during other labs to lessen patient visits. 
 
Note: This is a separate requirement for a ctDNA whole blood 
specimen for all patients registered to S1900C, regardless of 
whether or not there was a ctDNA blood collection for LUNGMAP. 
  
• 
Cycle 3 Day 1 (prior to treatment) 
• 
First progression after study treatment 
o 
Collection must be within 14 days after site learns of progression 
and prior to starting non-protocol treatment. 
• 
Off protocol treatment 
Note: If the first progression after study treatment and the off protocol treatment 
timepoints occur at the same time, only a single specimen is to be collected.  
 
c. 
Specimen Collection and Shipment Instructions 
 
Specimen must be logged via the SWOG Specimen Tracking System.  
 
Step 1: Check special tubes provided in kits to confirm liquid is clear and without 
cloudiness or crystals. 
 
Step 2: Label tubes with date of collection, patient identifiers as requested on the 
included labels (patient date of birth can be added as an extra identifier), 
and sub-study number. 
 


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Step 3: Collect two tubes of whole blood (8.5 mL per tube) 
o 
Prevent backflow: tubes contain chemical additives and it is important 
to avoid backflow into patient 
o 
Collect specimen by venipuncture 
o 
Fill tubes completely (8.5 mL per tube) 
 
Step 4: Remove the tube from adapter and immediately mix by gentle inversion 8 
to 10 times. Inadequate or delayed mixing may result in inaccurate test 
results. One inversion is a complete turn of the wrist, 180̊ and back, per 
the figure below. 
 
 
 
Step 5: Place specimen into the specimen collection kit. 
o 
Confirm each tube is labeled with the supplied labels indicating the 
date of collection and two unique patient identifiers (label included in 
kit). 
 
Step 6: Select “Ship this Shipment and Generate Packing List” in the SWOG 
Specimen Tracking System to generate the Packing List. A copy of the 
SWOG Specimen Tracking Packing List must be included in the shipment. 
Confirm that the tubes are labeled as specified on the Packing List. 
 
Step 7: Preferably on the same day of collection, ship via FedEx overnight delivery 
at ambient temperature. Do not freeze or refrigerate blood samples. Keep 
at 43-99̊ F (6-37̊ C). 
 
FMI accepts Saturday deliveries. If shipping on a Friday, please overnight 
shipment and mark for Saturday delivery. 
 
d. 
Specimen Usage 
 
Cell-free, circulating DNA will be isolated from the plasma component of the whole 
blood. Using a hybrid-capture, next-generation sequencing technology (developed 
by Foundation Medicine), alterations in clinically significant cancer genes 
(oncogenes and tumor suppressor genes) will be identified and quantitated relative 
to wild-type sequences. Tumor-specific alterations will include point mutations, 
small insertions and deletions, chromosomal rearrangements and copy 
number/amplification events in (LUNGMAP ctDNA Assay) including an 
assessment of tumor mutation burden (TMB) will be conducted using ctDNA. A full 
proposal will be developed, reviewed, and approved by SWOG and CTEP once 
funding has been obtained. 
 
The ctDNA results are for research purposes and will not be shared with the 
investigator or patient.  
 
15.4 
Translational Medicine and Banking (OPTIONAL FOR PATIENT) 
 


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Specimens for translational medicine and banking (submitted to the SWOG Biospecimen 
Bank – Solid Tissue, Myeloma and Lymphoma Division, Lab #201) are considered optional 
for the patient: 
 
a. 
With patient’s consent, specimens must be collected and submitted as follows: 
 
1. 
Buffy Coat and Plasma: 
 
Specimens must be collected at the following times. 
 
• 
Pre-study (after consenting and prior to treatment initiation on 
sub-study) 
Note: If a patient provided buffy coat and plasma for 
LUNGMAP and the blood collection was within 42 days prior 
to the sub-study registration, then no additional pre-study 
blood specimen is required. 
• 
Cycles 2, 3, 4 (at the same time as lab collection, prior to the 
start of cycle treatment) - Patients that go off protocol 
treatment are not required to continue to submit specimens. 
• 
First progression after study treatment. 
 
Collect approximately 8-10 mL of blood in EDTA tubes. Blood should be 
processed within one hour after venipuncture. If immediate processing 
within this time frame is not possible, then refrigerate (4°C) blood in EDTA 
tubes. The approximate time from collection to processing should be 
recorded as part of the patient’s source documentation. EDTA tubes must 
be centrifuged at 800 x g for 10 minutes at 4˚C for the collection of plasma. 
[Note: Sites that do not have a refrigerated centrifuge should spin at room 
temperature and ensure specimens are placed on ice (regular, not dry) 
immediately after being drawn and process rapidly.] Using a pipette, 
transfer the plasma to a 15-mL centrifuge tube. Remove the buffy coat 
layer (thin white or gray layer of cells between the plasma and red blood 
cells) and split between two appropriately labeled 2-mL cryovials.  
 
Spin the plasma in the 15-mL centrifuge tube at 800 x g for an additional 
10 minutes. Avoiding any pelleted material, pipette the plasma into labeled 
cryovials at 0.5 ml aliquots. Plasma must be clear before freezing; no cells 
or debris should be present.  
 
Plasma and buffy coat vials must be placed upright in a -80˚C freezer 
immediately after processing to ensure long-term viability.   
 
Frozen plasma and buffy coat specimens must be shipped to the SWOG 
Biospecimen Bank on dry ice. Frozen specimens may be shipped in 
batches – refer to Section 15.4b. 
 
b. 
Specimen Collection, Submission, and Labeling Instructions 
 
Samples for multiple patients may be shipped in batches to the SWOG 
Biospecimen Bank – Solid Tissue, Myeloma and Lymphoma Division, Lab #201, 
at least every 3 months (if not more frequently), with a maximum of 5 patients’ 
samples included per batch. 
 
For additional information about labeling and shipping instructions for frozen 
plasma and buffy coat specimens, refer to the SWOG Specimen Submission 
webpage 
(https://www.swog.org/clinical-trials/biospecimen-
resources/biospecimen-processing-and-submission-procedures). 


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1. 
Liquid specimens must be labeled with the following: 
• 
SWOG patient number 
• 
Patient initials 
• 
Collection date (date the specimen was collected from the patient) 
• 
Specimen type (e.g. blood, serum, etc.) 
 
 
c. 
Specimen collection kits are not being provided for this submission; sites must use 
institutional supplies. 
 
15.5 
Radiology Review (REQUIRED) 
 
CT, PET/CT, and/or MRI images must be locally read and interpreted by the local site 
radiology service.  Imaging exams must then be submitted to the Imaging and Radiation 
Oncology Core (IROC) at Ohio via TRIAD Imaging Submission procedures for central data 
collection and quality control (QC) check as well as central review. 
 
a. 
CT, PET/CT, and/or MRI images must be submitted to IROC Ohio for central 
review. See Section 7.3 and 9.0 for timepoints and details.  
 
The same imaging modality used for the pre-treatment exam must be used for the 
post-treatment exams (see LUNGMAP Section 10.1). Each exam should be 
performed per Appendix 18.2f of LUNGMAP. IROC will perform a QC of the 
imaging exams.   
 
Note: PET-CT: At present, the low dose or attenuation correction CT portion of a 
PET-CT is not always of optimal diagnostic CT quality for use with RECIST 
measurements. However, if the site can document that the CT performed as part 
of a PET-CT is of identical diagnostic quality to a diagnostic CT, then the CT portion 
of the PET-CT can be used for RECIST measurements and can be used 
interchangeably with stand-alone CT. The slice thickness of 0.5 cm or less is highly 
recommended. If CT scans have slice thickness > 0.5 cm, the minimum size for a 
measurable lesion should be twice the slice thickness. 
 
Clinical management and treatment decisions will be made by the treating 
physician based on local site assessments and other clinically appropriate 
considerations. 
 
Central review of scans will not be triggered if the study will not be submitted to the 
FDA for FDA approval of the investigational therapy.  Central review of scans will 
be triggered only if deemed necessary for FDA evaluation.  A detailed description 
of the central radiology review, including image acquisition parameters and image 
submission instructions, can be found in Appendix 18.2f of LUNGMAP. 
 
b. 
TRIAD Digital Image Submission  
 
Transfer of Images and Data (TRIAD) is the American College of Radiology’s 
(ACR) image exchange application.  TRIAD provides sites participating in clinical 
trials a secure method to transmit images. TRIAD anonymizes and validates the 
images as they are transferred. 
 
TRIAD will be the sole means of image transfer to the IROC Ohio. TRIAD should 
be installed prior to study participant enrollment to ensure prompt secure, 
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1. 
TRIAD Access Requirements: 
 
• 
A valid and active CTEP-IAM account (see LUNGMAP Section 
13.2). 
• 
Registration and Credential Repository (RCR) registration type of: 
Associate (A), Associate Plus (AP), Non-Physician Investigator 
(NPIVR), or Investigator (IVR) registration type. Refer to the CTEP 
Registration Procedures section for instructions on how to request a 
CTEP-IAM account and complete registration in Registration and 
Credential Repository (RCR). 
• 
TRIAD Site User role on the NCTN or ETCTN roster.   
 
All individuals on the Imaging and Radiation Oncology Core provider roster have 
access to TRIAD, and may submit images for credentialing purposes, or for 
enrollments to which the provider is linked in OPEN. 
 
2. 
TRIAD Installation: 
 
To submit images, the individual holding the TRIAD Site User role will 
need to install the TRIAD application on their workstation. TRIAD 
installation documentation is available at:  
https://triadinstall.acr.org/triadclient/. 
 
This process can be done in parallel to obtaining your CTEP-IAM account 
and RCR registration. 
 
For questions, contact TRIAD Technical Support staff via email TRIAD-
Support@acr.org or 1-703-390-9858. 
 
16.0 
ETHICAL AND REGULATORY CONSIDERATIONS 
 
The following must be observed to comply with Food and Drug Administration regulations for the 
conduct and monitoring of clinical investigations; they also represent sound research practice. 
 
Informed Consent 
 
The principles of informed consent are described by Federal Regulatory Guidelines (Federal 
Register Vol. 82, No. 12, January 19, 2017) and the Office for Protection from Research Risks 
Reports:  Protection of Human Subjects (Code of Federal Regulations 45 CFR 46).  They must be 
followed to comply with FDA regulations for the conduct and monitoring of clinical investigations. 
 
Institutional Review 
 
This study must be approved by an appropriate institutional review committee as defined by Federal 
Regulatory Guidelines (Federal Register Vol. 82, No. 12, January 19, 2017) and the Office for 
Protection from Research Risks Reports: Protection of Human Subjects (Code of Federal 
Regulations 45 CFR 46). 
 
Drug Accountability 
 
An investigator is required to maintain adequate records of the disposition of investigational drugs 
according to procedures and requirements governing the use of investigational new drugs as 
described in the Code of Federal Regulations 21 CFR 312 and the CTEP Investigator’s Handbook. 
 
Publication and Industry Contact 


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The agents supplied by CTEP, DCTD, NCI used in this protocol are provided to the NCI under 
Collaborative Agreements (CRADA, CTA, CSA) between the Pharmaceutical Companies 
(hereinafter referred to as "Collaborators") and the NCI Division of Cancer Treatment and 
Diagnosis.  Therefore, the following obligations/guidelines in addition to the provisions in the 
"Intellectual Property Option to Collaborator"  
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm) contained within the 
terms of award apply to the use of the Agents in this study: 
 
a. 
Agents may not be used for any purpose outside the scope of this protocol, nor can Agents 
be transferred or licensed to any party not participating in the clinical study.  Collaborators 
data for Agents are confidential and proprietary to Collaborators and shall be maintained 
as such by the investigators.  The protocol documents for studies utilizing Agents contain 
confidential information and should not be shared or distributed without the permission of 
the NCI.  If a copy of this protocol is requested by a patient or patient’s family member 
participating on the study, the individual should sign a confidentiality agreement. A suitable 
model agreement can be downloaded from: http://ctep.cancer.gov.  
 
b. 
For a clinical protocol where there is an investigational Agent used in combination with 
(an)other investigational Agent(s), each the subject of different Collaborative Agreements, 
the access to and use of data by each Collaborator shall be as follows (data pertaining to 
such combination use shall hereinafter be referred to as "Multi-Party Data"): 
 
1. 
NCI will provide all Collaborators with written notice regarding the existence and 
nature of any agreements governing their collaboration with NCI, the design of the 
proposed combination protocol, and the existence of any obligations which would 
tend to restrict NCI's participation in the proposed combination protocol. 
 
2. 
Each Collaborator shall agree to permit use of the Multi-Party Data from the clinical 
trial by any other Collaborator solely to the extent necessary to allow said other 
Collaborator to develop, obtain regulatory approval or commercialize its own 
investigational Agent. 
 
3. 
Any Collaborator having the right to use the Multi-Party Data from these trials must 
agree in writing prior to the commencement of the trials that it will use the Multi-
Party Data solely for development, regulatory approval, and commercialization of 
its own Agent. 
 
c. 
Clinical Trial Data and Results and Raw Data developed under a Collaborative Agreement 
will be made available exclusively to Collaborators, the NCI, and the FDA, as appropriate 
and unless additional disclosure is required by law or court order as described in the IP 
Option to Collaborator 
(http://ctep.cancer.gov/industryCollaborations2/intellectual_property.htm). Additionally, all 
Clinical Data and Results and Raw Data will be collected, used and disclosed consistent 
with all applicable federal statutes and regulations for the protection of human subjects, 
including, if applicable, the Standards for Privacy of Individually Identifiable Health 
Information set forth in 45 C.F.R. Part 164. 
 
d. 
When a Collaborator wishes to initiate a data request, the request should first be sent to 
the NCI, who will then notify the appropriate investigators (Group Chair for Cooperative 
Group studies, or PI for other studies) of Collaborator's wish to contact them. 
 
e. 
Any data provided to the Collaborators for Phase III studies must be in accordance with 
the guidelines and policies of the responsible Data Monitoring Committee (DMC), if there 
is a DMC for this clinical trial. 
 


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f. 
Any manuscripts reporting the results of this clinical trial must be provided to CTEP by the 
Group office for Cooperative Group studies or by the principal investigator for non-
Cooperative Group studies for immediate delivery to Collaborators for advisory review and 
comment prior to submission for publication.  Collaborators will have 30 days from the date 
of receipt for review.  Collaborator shall have the right to request that publication be delayed 
for up to an additional 30 days in order to ensure that Collaborator's confidential and 
proprietary data, in addition to the Collaborator’s intellectual property rights, are protected.  
Copies of abstracts must be provided to CTEP for forwarding to Collaborators for courtesy 
review as soon as possible and preferably at least three (3) days prior to submission, but 
in any case, prior to presentation at the meeting or publication in the proceedings.  Press 
releases and other media presentations must also be forwarded to CTEP prior to release.  
Copies of any manuscript, abstract and/or press release/media presentation should be sent 
to: 
 
E-mail:  ncicteppubs@mail.nih.gov  
 
The Regulatory Affairs Branch will then distribute them to the Collaborators.  No 
publication, manuscript or other form of public disclosure shall contain any of the 
Collaborator's confidential/proprietary information. 
 
Monitoring 
 
This study will be monitored by the Clinical Data Update System (CDUS) Version 3.0.  Cumulative 
CDUS data will be submitted quarterly to CTEP by electronic means.  Reports are due January 31, 
April 30, July 31 and October 31. 
 
Trial Master File 
  
This study is an FDA registration study; therefore, all participating sites should be FDA "inspection 
ready". This entails maintaining a Trial Master File that includes essential documents that may be 
subject to FDA oversight. A list of essential documents is available on the SWOG website under 
QA/Audits, https://swog.org/Visitors/QA/Index.asp.  
 
Confidentiality 
 
Please note that the information contained in this protocol is considered confidential and should 
not be used or shared beyond the purposes of completing protocol requirements until or unless 
additional permission is obtained. 
 
17.0 
BIBLIOGRAPHY 
 
1  
The Cancer Genome Atlas Research Network. Comprehensive molecular profiling of lung 
adenocarcinoma., Nature, 2014: 543-550. 
 
2  
Skoulidis F, Goldberg M E, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018 Jul;8(7):822-835. 
 
3  
Shackelford, D B, Shaw, R J. The LKB1-AMPK pathway: metabolism and growth control in tumor 
suppression. Nat Rev Cancer, 2009: 563-75. 
 
4  
Skoulidis F, Goldberg M E, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018 Jul;8(7):822-835. 
 
5  
Shackelford, D B, Shaw, R J. The LKB1-AMPK pathway: metabolism and growth control in tumor 
suppression. Nat Rev Cancer, 2009: 563-75. 
 


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6  
Skoulidis F, Goldberg M E, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018 Jul;8(7):822-835. 
 
7  
Skoulidis F, Elamin Y, Papadimitrakopoulou V, et al. Impact of major co-mutations on the immune 
contexture and response of KRAS-mutant lung adenocarcinoma to immunotherapy. WCLC, 2016. 
 
8  
Skoulidis F, Hellman M D, Awad M M, et al. STK11 co-mutations to predict for de novo resistance 
to PD-1/PD-L1 axis blockade in KRAS-mutant lung adenocarcinoma. ASCO, 2017. 
 
9  
Skoulidis F, Albacker LA, Hellmann MD, et al. STK11 Loss of Function Genomic Alterations Predict 
Primary Resistance to PD-1/PD-L1 Axis Blockade in KRAS-Mutant-NSCLC. WCLC, 2017. 
 
10  
Skoulidis F, Goldberg M E, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018 Jul;8(7):822-835. 
 
11  
Skoulidis F, Byers LA, Diao L, et al. Co-occurring genomic alterations define major subsets of 
KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic 
vulnerabilities. Cancer Discovery, 2015: 860-77. 
 
12  
Skoulidis F, Denning W, Diao L, et al. Association of inactivation of STK11 with a suppressive 
immune mincroenvironment in lung adenocarcinoma. ASCO, 2015. 
 
13  
Koyama S, Akbay EA, Li YY, et al. STK11 deficiency promotes neutrophil recruitment and 
proinflammatory cytokine production to suppress t-cell activity in the lung tumor microenvironment. 
Cancer Res, Mar 1;76(5):999-1008. 
 
14  
Skoulidis F, Hellman M D, Awad M M, et al. STK11 co-mutations to predict for de novo resistance 
to PD-1/PD-L1 axis blockade in KRAS-mutant lung adenocarcinoma. ASCO, 2017. 
 
15  
Skoulidis F, Goldberg ME, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018. 
 
16  
Skoulidis F, Albacker LA, Hellmann MD, et al. STK11 Loss of Function Genomic Alterations Predict 
Primary Resistance to PD-1/PD-L1 Axis Blockade in KRAS-Mutant-NSCLC. WCLC, 2017. 
 
17  
Skoulidis F, Goldberg M E, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018 Jul;8(7):822-835. 
 
18  
Skoulidis F, Goldberg ME, Greenawalt D M et al. STK11 mutations and PD-1 inhibitor resistance 
in KRAS-mutant lung adenocarcinoma. Cancer Discovery, 2018. 
 
19  
Koyama S, Akbay EA, Li YY, et al. STK11 deficiency promotes neutrophil recruitment and 
proinflammatory cytokine production to suppress t-cell activity in the lung tumor microenvironment. 
Cancer Res, Mar 1;76(5):999-1008.  
 
20  
Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes anti-tumor 
immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discovery, 
2019. 
 
21  
Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes anti-tumor 
immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discovery, 
2019. 
 
22  
Khoo LT, Chen LY. Role of the cGAS-STING pathway in cancer development and oncotherapeutic 
approaches. EMBO Reports (2018) 19: e46935.  
 


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23  
Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes anti-tumor 
immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discovery, 
2019. 
 
24  
Corrales L, McWhirter SM et al. The host STING pathway at the interface of cancer and immunity. 
J Clin Invest. 2016 Jul 1; 126(7):2404-11. 
 
25  
Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes anti-tumor 
immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discovery, 
2019. 
 
26  
Bauer S, Groh V, Wu J, et al. Activation of NK cells and T cells by NKG2D, a receptor for stress-
inducible MICA. Science. 1999 Jul 30;285(5428): 727-9. 
 
27  
Skoulidis F, Byers LA, Diao L, et al. Co-occurring genomic alterations define major subsets of 
KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic 
vulnerabilities. Cancer Discovery, 2015: 860-77. 
 
28  
Galan-Cobo A, et al. LKB1 and KEAP1/NRF2 pathways cooperatively promote metabolic 
reprogramming with enhanced glutamine dependence in KRAS-mutant lung adenocarcinoma. 
Cancer Research, 2019 
 
29  
Wang YS, Chen J, et al. LKB1 is a DNA damage response protein that regulates cellular sensitivity 
to PARP inhibitors. (2016) Oncotarget, 7 (45), pp. 73389-73401. 
 
30  
Sen T, Rodriguez BL, Chen L, et al. Targeting DNA damage response promotes anti-tumor 
immunity through STING-mediated T-cell activation in small cell lung cancer. Cancer Discovery, 
2019. 
 
31  
Liu Y, Marks K, et al. Metabolic and Functional Genomic Studies Identify Deoxythymidylate Kinase 
as a Target in LKB1-Mutat Lung Cancer. Cancer Discovery, 2013; 3(8):870-879. 
 
32  
Richer AL, Cala JM, et al. WEE1 Kinase Inhibitor AZD1775 Has Preclinical Efficacy in LKB1-
Deficient Non-Small Cell Lung Cancer. Cancer Research, 2017; 77(17):4663-4672. 
 
33  
Gupta R et al. LKB1 preserves genome integrity by stimulating BRCA1 expression. Nucleic Acids 
Res, 2015: 259-71. 
 
34  
Barlesi F, Vansteenkiste J, Spigel D et al. Avelumab versus docetaxel in patients with platinum-
treated advanced non-small-cell lung cancer (JAVELIN Lung 200): an open-label, randomized, 
phase 3 study. Lancet Oncol. 2018 Sep 21 [Epub ahead of print]. 
 
35  
De Bono J, Ramanathan RK, Mina L et al. Phase I, Dose-Escalation, Two-Part Trial of the PARP 
Inhibitor Talazoparib in Patients with Advanced Germline BRCA1/2 Mutations and Selected 
Sporadic Cancers. Cancer Discov. 2017 Jun;7(6):620-629). 
 
 
 
 


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18.0 
APPENDIX 
 
18.1 
New York Association Classification 
 
18.2 
Monitoring Plan 
 
18.3 
Instructions for the SWOG Biospecimen Bank 
18.4 
Patient Diary – Talazoparib 
18.5 
Patient Drug Information Handout and Wallet Card 
18.6 
Site Temperature Excursion Report Form 
 
 
 
 
 
 


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18.1 
New York Heart Association Classification 
 
 
 
 
Need for 
Physical Ability 
 
Class 
Cardiac Symptoms 
Limitations 
Additional Rest* 
To Work** 
 
 
 
I 
None 
None 
None 
Full Time 
 
II 
Only moderate 
Slight 
Usually only slight 
Usually full time 
 
 
 
or occasional 
 
III 
Defined, with less 
Marked 
Usually moderate 
Usually part time 
 
than ordinary 
 
activity 
 
IV 
May be present 
Extreme 
Marked 
Unable to work 
 
even at rest, & any 
 
activity increases 
 
discomfort 
 
* 
To control or relieve symptoms, as determined by the patient, rather than as advised by 
the physician. 
** 
At accustomed occupation or usual tasks. 
 
 


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18.2 
Monitoring Plan 
 
For information on the LUNGMAP Monitoring Plan, please refer to LUNGMAP Appendix 
18.2. 
 
 
 
 
 
 
 


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18.3 
Instructions for the SWOG Biospecimen Bank 
 
Frozen Plasma and Buffy Coat 
The SWOG Biospecimen Bank will receive frozen plasma and buffy coat at up to 5 time 
points per patient. Upon receipt, the Bank will accession, barcode, and Bank specimens in 
a -80°C freezer.   
 
Formalin-fixed Paraffin-Embedded (FFPE) Tissue 
The SWOG Biospecimen Bank will receive FFPE specimens as either blocks or 
slides/sections at 1time point per patient. Upon receipt, the Bank will accession, barcode, 
and Bank specimens at ambient temperature.   
 
At the end of the study, the Bank will receive notification from the SWOG Statistics and 
Data Management Center to distribute specimens for testing.   
 
 
 


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18.4  
Patient Diary – Talazoparib 
 
 
 
 
SWOG Study: S1900C 
 
Site Personnel Instructions 
 
• 
Patient numbers should be recorded on the bottle label in the spaces provided by 
site personnel at the time of assignment to patient. 
 
• 
Ensure that patient clearly understands the guidelines for self-medication. 
 
• 
Patient should be given enough supply to last until their next study visit. 
 
• 
Unused drug and/or empty bottles should be returned to the site at the next study 
visit. 
 
Please review the following with the patient: 
 
• 
Cycle, Start Date and Start Time information with the patient. If possible, have the 
patient document their first dose in the appropriate calendar box. 
 
• 
Patients and their caregivers should be advised that talazoparib is a toxic 
substance and that gloves should always be used when handling the talazoparib 
capsules.  
 
• 
Patient’s dose schedule: Talazoparib should be taken once a day, as close to the 
same time each day as possible (preferably in the morning). Provide patient with 
the instructions on how to document this schedule appropriately. 
 
• 
Talazoparib can be taken with or without food.  
 
• 
How to document vomited, missed, or skipped doses in the specific areas 
provided. 
 
 


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SWOG Patient ID __________ Patient Initials (L, F, M) __________ SWOG Study # __________ 
Cycle: __________ 
Start Date: __________       Start Day (circle one): Sun  M  Tu  W  Th  F  Sat 
Instructions for the patient: 
Record the date and time of the talazoparib capsules you take each day on this calendar. You should: 
• 
Always use gloves when handling the talazoparib capsules.  
• 
Take your medication once a day, at the same time each day (preferably in the morning). 
• 
Put the date in the box on the calendar and note the time of the dose each day.  
• 
Check off if the dose was taken or not. 
• 
Talazoparib can be taken with or without food.  
• 
Swallow the capsules whole. Do not chew. Do not take any capsules that are broken or cracked. 
• 
Document any changes to taking the doses in the comments section provided below.  
- 
If you forget to take the dose at your usual time, dose can be taken as long as there is 12 
hours before your dose the next day. 
- 
If you miss a day’s dose, do not “make it up.” Mark it as a “missed” dose with the date and 
time. Take the normal dose the next day.   
- 
If you vomit a dose, the dose should not be re-taken. Record this as a “vomited” dose with the 
date and time. 
- 
If you accidentally take an extra dose during a day, skip the next day’s dose. Record this as 
an “extra dose.”  
• 
If you develop any side effects from the capsule, mark the side effect on the comments section 
provided with the date and time you developed the side effect. 
Storage: 
Talazoparib capsules are to be stored at controlled room temperature, 59-86°F. 
Date 
Was dose taken? 
What time? 
Comments 
   
 Day 1    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 2    ____/____/____ 
   □ Yes         □ No 
   ____:____ am/pm  
   
 Day 3    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 4    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 5    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 6    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 7    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 8    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 9    ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 10   ____/____/____ 
 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 11   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 


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 Day 12   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 13   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 14   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 15   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 16   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 17   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 18   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 19   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 20   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 21   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 22   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 23   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 24   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 25   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 26   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 27   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
   
 Day 28   ____/____/____ 
   □ Yes         □ No  
   ____:____ am/pm  
 
 
 
 


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18.5 
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 
 
Patient 
Name: 
      
Diagnosis:  
      
Trial #: 
      
Study 
Doctor: 
      
Study 
Doctor 
Phone #: 
      
Study 
Drug(s): 
Talazoparib + 
Avelumab 
 
Please show this paper to all your healthcare providers (doctors, physician assistants, nurse practitioners, 
pharmacists), and tell them you are taking part in a clinical trial sponsored by National Cancer Institute. 
 
To the patient: Take this paper with you to your medical appointments and keep the attached 
information card in your wallet. These are the things that you need to know: 
 
Talazoparib and avelumab may interact with other drugs which can cause side effects. For this reason, it 
is very important to tell your doctors about all your medicines, including: 
• medicines you are taking before this clinical trial,  
• medicines you start or stop taking during this clinical trial,  
• medicines you buy without a prescription (over-the-counter remedy),  
• herbal supplements such as St. John’s Wort.   
 
Please 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 your healthcare providers need to know: 
• The proteins in question are P-gp inhibitors and BCRP. Talazoparib is moved in and out of 
cells/organs by these transport proteins and may be affected by other drugs that strongly inhibit 
these transport proteins. Use of strong P-gp and BCRP inhibitors should be avoided. Caution 
should be used for coadministration of other P-gp inhibitors (e.g., amiodarone, azithromycin, 
captopril, carvedilol, clarithromycin, conivaptan, cyclosporine, diltiazem, erythromycin, felodipine, 
lopinavir, quercetin), P-gp inducers (e.g., avasimibe, carbamazepine, phenytoin, St John’s wort), or 
BCRP inhibitors (e.g., cyclosporine, eltrombopag, and gefitinib). 
• Patients must not receive any live attenuated vaccinations while on study treatment. 
 
These are the things that you and your healthcare providers need to know:  
 
Talazoparib must be used very carefully with other medicines that use certain transport proteins to be 
effective.  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 inhibitors of the 
transport proteins 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.  
• 
Make sure your doctor knows to avoid certain prescription medications.  
• 
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 _____________________________________. 


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Patient Drug Interaction Wallet Card 
 
 
 
 
 
EMERGENCY 
INFORMATION 
 
DRUG INTERACTIONS  
Show this card to all of your 
healthcare providers. Keep it 
with you in case you go to the 
emergency room. 
Tell your doctors before you start 
or stop any medicines. 
Check with your doctor or 
pharmacist if you need to use an 
over-the-counter medicine or 
herbal supplement! 
Carry this card with you at all times   
Talazoparib interacts with transport proteins P-gp and BCRP and 
must be used very carefully with other medicines that interact with 
this transporter. 
Patient Name:       
Use caution and avoid the 
following drugs if possible:  
 
Talazoparib may interact with 
drugs that use certain transport 
proteins in your body.  
 
Avoid any medicines that are 
considered strong inhibitors of P-
gp and BCRP while taking 
talazoparib. 
Your healthcare providers should be aware of any medicines that are 
considered strong inhibitors of P-gp and BCRP. 
Diagnosis:       
Study Doctor:       
Study Doctor Phone #:       
NCI Trial #:       
Before prescribing new medicines, your health care provider should 
check a frequently-updated medical reference for a list of drugs to 
avoid or contact your study doctor. 
Study Drug(S):       
 
             Version SEP 2019 
 
For more information: 1-800-4-CANCER 
For more information: 1-800-4-CANCER 
For more information: 1-800-4-
CANCER 
For more information: 1-800-4-CANCER 
cancer.gov | clinicaltrials.gov 
cancer.gov | clinicaltrials.gov 
cancer.gov | clinicaltrials.gov 
cancer.gov | clinicaltrials.gov 
 
 


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18.6  
Site Temperature Excursion Report Form 
 
For information on talazoparib and avelumab storage temperature excursion, please refer 
to Section 3.0 and submit this form to Pfizer.  
Form Version: 23Dec2016 
Submit completed form to: GCSTempExcursionSupport@pfizer.com 
 
SECTION 1.  Study Information  
Protocol Number 
 
Site Number 
 
Country  
 
Investigational Product Name or 
Number1  
 
Principal Investigator First and 
Last Name / Title 
 
Form Completed by <First and 
Last Name / Title (Printed)>  
 
Date: <dd-Mmm-yyyy> 
 
 SECTION 2.   Investigational Product and Dispensing Information  
Date of Temperature Excursion2  
<dd-Mmm-yyyy> 
Temperature Log that Shows the 
Date and Duration of this 
Excursion Only3  
Provide relevant document(s) as a separate attachment when submitting this form.  
Lot (PReq) Number of 
Impacted IP4  
<format XX-YYYYYY> 
Kit Number(s) and/or Container 
Number(s) of Impacted 
Investigational Product (if 
applicable)5 
 
Were any Affected Kit(s) and/or 
Container(s) Dispensed to 
Subjects6  
  
  No      
  Yes 
If yes – List the affected Kit Numbers and/or Container Numbers and dates they were 
dispensed. 
  
Kit and/or Container Number 
Date Dispensed  
 
 
 
 
 
 
              (dd-Mmm-yyyy) 
N/A 
N/A 
N/A 
N/A 
Date of Next Subject Visit7 if 
applicable 
<dd-Mmm-yyyy> 
Distribution and/or IRT System 
Used to Distribute and/or Dispense 
investigational product 
(N/A for PCH) 
 
 
Storage Condition on Label 
 


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Lot(s)/Kit(s) that had Excursion 
are Now Returned/Maintained in 
Acceptable Storage Condition 
  No     
  Yes    
 
SECTION 3.  Temperature Excursion Decision (To be completed by Pharmaceutical Sciences (PharmSci)/ PCH supply chain 
only)  
Kit Number(s) and/or Container 
Number(s) of Impacted 
Investigational Product (if 
applicable) 
Summary of Excursion  
Investigational Product Acceptable for Use  
 
 
  Acceptable      
  Not Acceptable 
 
 
  Acceptable      
  Not Acceptable 
 
 
  Acceptable      
  Not Acceptable 
Form Completed by < 
PharmSci/PCH Representative 
First and Last Name/Title 
(Printed)> 
 
Date  
(dd-Mmm-yyyy)   
 
 
 

ICF_001.pdf: 
Readability Statistics: 
S1900C 
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Research Study Informed Consent Document 
 
Study Title for Participants: Testing the Combination of Talazoparib plus Avelumab for 
Patients with Advanced Non-Squamous Non-Small Cell Lung Cancer 
 
LUNGMAP, “A Master Protocol to Evaluate Biomarker-Driven Therapies and 
Immunotherapies in Previously-Treated Non-Small Cell Lung Cancer (Lung-MAP 
Screening Study)” 
 
Official Study Title for Internet Search on http://www.ClinicalTrials.gov:  
 
S1900C, “A Phase II Study of Talazoparib Plus Avelumab In Patients with Stage IV or 
Recurrent Non-Squamous Non-Small Cell Lung Cancer Bearing Pathogenic STK11 
Genomic Alterations (Lung-MAP Sub-Study)” 
 (NCT 04173507) 
 
Overview and Key Information  
 
What am I being asked to do? 
 
We are asking you to take part in this research study because you have non-squamous non-small 
cell lung cancer. Your tumor sample has been found to have a mutation in the STK11 gene, for 
which there is a treatment option.  
 
This study has public funding from the National Cancer Institute (NCI), part of the National 
Institutes of Health (NIH) in the United States Department of Health and Human Services. We 
do research studies to try to answer questions about how to prevent, diagnose, and treat diseases 
like cancer. 
 
 
Taking part in this study is your choice.  
 
You can choose to take part, or you can choose not to take part in this study.  You also can 
change your mind at any time.  Whatever choice you make, you will not lose access to your 
medical care or give up any legal rights or benefits. 
 
This document has important information to help you make your choice. Take time to read it.  
Talk to your doctor, family, or friends about the risks and benefits of taking part in the study.  
It’s important that you have as much information as you need and that all your questions are 
answered.  See the “Where can I get more information?” section for resources for more clinical 
trials and general cancer information. 
 


 
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Why is this study being done? 
 
This study is being done to answer the following question:  
 
Can we increase the ability of your immune system to fight lung cancer and lower the chance of 
your lung cancer growing or spreading by using a combination of talazoparib and avelumab? 
 
We are doing this study because we want to find out if this approach is better or worse than the 
usual approach for your non-squamous non-small cell lung cancer.  The usual approach is 
defined as care most people get for their non-squamous non-small cell lung cancer. 
 
What is the usual approach to my lung cancer? 
 
The usual approach for patients who are not in a study is treatment with other cancer directed 
treatments such as chemotherapy and combinations of chemotherapy with drugs that target tumor 
blood vessels. Your doctor can explain which treatment may be best for you.  These treatments 
can reduce symptoms and may stop the tumor from growing for a few months or longer. 
 
What are my choices if I decide not to take part in this study? 
 
• You may choose to have the usual approach described above. 
• You may choose to take part in a different research study, if one is available. 
• You may choose not to be treated for cancer. 
• You may choose to only get comfort care to help relieve your symptoms and not get 
treated for your cancer.   
 
What will happen if I decide to take part in this study? 
 
If you decide to take part in this study, you will get the study drugs talazoparib and avelumab, 
until your disease gets worse or the side effects become too severe. Talazoparib and avelumab 
are drugs that may increase the ability of your immune system to fight lung cancer.  
 
After you finish your study treatment, your doctor will continue to follow your condition for up 
to three years from the time you went on study and watch you for side effects. If your disease has 
not gotten worse, follow up visits will occur every 3 months. If your disease has gotten worse, 
follow up visits will occur every 6 months for 2 years, then at the end of the 3 years from the 
time you go on study. At the follow-up visits you will have a physical exam, blood tests, and 
scans. Your doctor may give you other tests or procedures if they think they are needed for the 
regular care of your disease. 
 
Should your disease worsen, you have the option to participate in a different treatment study. As 
before, the new treatment study that you will be offered will depend on a combination of the 
results of the previous testing done on your tumor sample and the sub-studies available. If the 
tests show that your tumor has more than one biomarker that qualifies you for different treatment 


 
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studies, the sub-study you will be offered to participate in will be chosen by chance 
(randomization). A treatment study may be available even if your tumor does not have any 
additional biomarkers being tested or if you were not eligible to participate in the other 
(randomly assigned) sub-studies.  
  
What are the risks and benefits of taking part in this study? 
 
There are both risks and benefits to taking part in this study.  It is important for you to think 
carefully about these as you make your decision.     
 
Risks 
 
We want to make sure you know about a few key risks right now.  We give you more 
information in the “What risks can I expect from taking part in this study?” section. 
 
If you choose to take part in this study, there is a risk that the study approach may not be as good 
as the usual approach for your cancer at shrinking or stabilizing your cancer.   
 
There is also a risk that you could have side effects from the study drugs. These side effects may 
be worse and may be different than you would get with the usual approach for your cancer.   
 
Some of the most common side effects that the study doctors know about are: 
• Anemia 
• Nausea 
• Tiredness 
• Bruising, bleeding 
• Reaction during or following a drug infusion which may cause rash, low blood pressure 
 
There may be some risks that the study doctors do not yet know about.   
 
Benefits 
 
Recent scientific research indicates that the combination of talazoparib and avelumab has shrunk 
your type of cancer in a limited number of people and animals or in living human or living 
animal cells.   
 
However, it is not known that this combination will work in everyone with your cancer or help 
you live longer.  This study may help the study doctors learn things that may help other people in 
the future. 
 
If I decide to take part in this study, can I stop later? 
 
Yes, you can decide to stop taking part in the study at any time.  
 


 
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If you decide to stop, let your study doctor know as soon as possible.  It’s important that you stop 
safely. This may mean slowly stopping the study drugs so that there is not a sudden, unsafe 
change or risk to your health.  If you stop, you can decide if you want to keep letting the study 
doctor know how you are doing. 
 
Your study doctor will tell you about new information or changes in the study that may affect 
your health or your willingness to continue in the study. 
 
Are there other reasons why I might stop being in the study? 
 
Yes.  The study doctor may take you off the study if: 
 
• Your health changes and the study is no longer in your best interest. 
• New information becomes available and the study is no longer in your best interest. 
• You do not follow the study rules. 
• You become pregnant while on the study. 
• The study is stopped by the National Cancer Institute (NCI), Institutional Review Board 
(IRB), Food and Drug Administration (FDA), or study sponsor (SWOG Cancer Research 
Network).  The study sponsor is the organization who oversees the study.   
 
It is important that you understand the information in the informed consent before making 
your decision. Please read, or have someone read to you, the rest of this document. If there is 
anything you don’t understand, be sure to ask your study doctor or nurse. 
 
End of Overview and Key Information  
 
 
 


 
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What is the purpose of this study? 
 
There are several investigational treatments that are being tested in various sub-studies as part of 
this study. You will have already received the information on your biomarker testing. You have 
been assigned to this treatment study because your tumor has a mutation in the STK11 gene. For 
this treatment study, you will be assigned to treatment with a combination of investigational 
drugs called talazoparib and avelumab.  
 
Immunotherapy drugs (PD-1 and PD-L1 inhibitors) given as single therapies or in combination 
with chemotherapy do not appear to work as well in lung cancer cells with mutations in the 
STK11 gene versus those that do not have the mutation. This study is looking to test whether the 
combination of the medicine talazoparib and the immunotherapy drug avelumab will work better 
for lung cancers that have an STK11 mutation. 
 
Talazoparib, a drug known as a PARP inhibitor, may impair the growth of tumor cells by 
blocking their ability to repair damage to their DNA. Treatment with talazoparib may help the 
ability of the immune system to recognize and fight cancer. 
 
Avelumab, an immunotherapy drug called a PD-L1 blocking antibody, may help your immune 
system fight your cancer more effectively. 
 
This study will test the combination of these two drugs (talazoparib and avelumab) to see if they 
will be effective in previously treated advanced non-squamous non-small cell lung cancer 
patients like you who have a tumor(s) with a mutation in the STK11 gene. The STK11 gene 
provides instructions for making a tumor suppressor protein, which helps keep cells from 
growing and dividing too fast or in an uncontrolled way. When the STK11 gene is mutated, it is 
less able to keep cancer cells from growing. 
 
The purpose of this study is to test the good and bad effects of the combination of drugs called 
talazoparib and avelumab. Talazoparib and avelumab could shrink your cancer, but it could also 
cause side effects, which are described in the risks section below.  
 
The study doctors hope to learn if the treatment will shrink your cancer. Another purpose of this 
study is for the study doctors to learn if checking for the STK11 gene mutation is helpful in 
picking the right cancer treatments. 
 
The combination of talazoparib and avelumab are not approved by the FDA for use in advanced 
non-squamous non-small cell lung cancer.  There will be up to 44 people taking part in this 
study. 
 
What are the study groups? 
 
In this study, all participants will get the study drugs called talazoparib and avelumab. Treatment 
will be given in cycles, with each cycle lasting 28 days. You will receive treatment until your 
disease gets worse, the side effects become too severe or you desire to discontinue the study. 


 
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Treatment Schedule:  
• Talazoparib: You will take talazoparib by mouth once a day, at around the same time 
each day (preferably in the morning). It is important to swallow whole and not to chew 
the capsules. Talazoparib can be taken with or without food. Always use gloves when 
handling talazoparib capsules.  
• Avelumab: You will be given avelumab through your vein over 60 minutes, followed by 
a 30-minute observation time, once every two weeks, in a clinical setting. You will also 
receive an antihistamine and acetaminophen 30-60 minutes before you start the first four 
cycles of avelumab to help prevent allergic reactions. You may continue to receive an 
antihistamine and acetaminophen after four cycles.  
 
You will not be able to get additional doses of the drugs.  The combination of talazoparib and 
avelumab is not approved by the FDA for treatment of your disease. 
 
Patient Diary: You will be asked to complete a patient diary to track any late or missed doses 
while you are taking talazoparib. 
 
What exams, tests, and procedures are involved in this study? 
 
Before you begin the study, your doctor will review the results of your exams, tests, and 
procedures. This helps your doctor decide if it is safe for you to take part in the study. If you join 
the study, you will have more exams, tests, and procedures to closely monitor your safety and 
health. Most of these are included in the usual care you would get even if you were not in a 
study. 
 
Listed below are exams, tests, and procedures that need to be done as part of this study to 
monitor your safety and health, but may not be included in the usual care.  We will use them to 
carefully follow the effects of the study treatment, including preventing and managing side 
effects.  
 
These exams, tests, and procedures to monitor your safety and health include:   
 
• A blood test to check thyroid function will be done every other cycles  
 
Some exams, tests, and procedures are a necessary part of the research study but would not be 
included in usual care.  Listed below are procedures that will be done for research purposes only.  
 
• Blood Test (circulating tumor DNA) at up to four timepoints: before you begin the study, 
on Cycle 3 Day 1 prior to treatment, if your disease becomes worse, and when you stop 
study treatment. 
You will be required to have about 1.5 tablespoons of your blood collected for the 
circulating tumor DNA testing. Circulating tumor DNA is found in the bloodstream and 
refers to DNA that comes from cancerous cells and tumors. An attempt will be made to 
do this blood draw at the same time as other blood draws. There is a chance that you will 
have another stick to obtain the blood. This blood will be tested for DNA not normally 


 
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found in cells but that is present in your blood because it has been released from the 
tumors in your body. The results of this blood test are for research purposes. You and 
your doctor will not receive the results of this blood test. The information collected will 
help the study doctors learn about tumor abnormalities that may play a role in tumor 
development.  
 
 
What risks can I expect from taking part in this study? 
 
General Risks 
 
If you choose to take part in this study, there is a risk that talazoparib and avelumab may not be 
as good as the usual approach for treating your cancer.   
 
You also may have the following discomforts: 
 
• Spend more time in the hospital or doctor’s office. 
• Be asked sensitive or private questions about things you normally do not discuss. 
• May not be able to take part in future studies.  
 
The drugs used in this study could be very harmful to an unborn or newborn baby.  There may be 
some risks that doctors do not yet know about.  It is very important that you check with your 
study doctor about what types of birth control or pregnancy prevention to use during the study 
and for 7 months after you have stopped taking talazoparib and avelumab. Do not donate sperm 
while taking part in this study and for 4 months after your last dose of study treatment. 
 
Blood Draw Risks 
 
Common side effects of a blood draw are a small amount of bleeding at the time of the blood 
draw, brief pain, and maybe a bruise.  
 
Side Effect Risks 
 
The drugs (talazoparib and avelumab) used in this study may affect how different parts of your 
body work such as your liver, kidneys, heart, and blood.  The study doctor will test your blood 
and let you know if changes occur that may affect your health. 
 
There is also a risk that you could have other side effects from the study drugs. 
 
Here are important things to know about side effects: 
 
1. The study doctors do not know who will or will not have side effects. 
2. Some side effects may go away soon, some may last a long time, and some may never go 
away. 
3. Some side effects may make it hard for you to have children. 


 
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4. Some side effects may be mild.  Other side effects may be very serious and even result in 
death. 
 
You can ask your study doctor questions about side effects at any time.  Here are important ways 
to make side effects less of a problem: 
 
• If you notice or feel anything different, tell your study doctor.  He or she can check to see 
if it is a side effect. 
• Your study doctor will work with you to treat your side effects. 
• Your study doctor may adjust the study drugs to try to reduce side effects. 
 
Drug Risks 
 
The tables below show the most common and most serious side effects doctors know about.  
Keep in mind that there might be other side effects doctors do not yet know about.  If important 
new side effects are found, the study doctor will discuss these with you. 
 
Possible Side Effects of Talazoparib  
(Table Version Date: October 24, 2020) 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving talazoparib, more than 20 and up to 100 may have: 
• 
Anemia which may require blood transfusion 
• 
Diarrhea, nausea, vomiting 
• 
Tiredness 
• 
Bruising, bleeding 
• 
Headache 
• 
Hair loss 
 
OCCASIONAL, SOME MAY BE SERIOUS   
In 100 people receiving talazoparib, from 4 to 20 may have: 
• 
Pain 
• 
Constipation, heartburn 
• 
Sores in the mouth which may cause difficulty swallowing 
• 
Fever 
• 
Infection, especially when white blood cell count is low 
• 
Loss of appetite 
• 
Dizziness 
 
RARE, AND SERIOUS   
In 100 people receiving talazoparib, 3 or fewer may have: 
• 
Cancer of bone marrow caused by chemotherapy 
• 
Damage to the bone marrow (irreversible) which may cause infection, bleeding, may require 
transfusions 
• 
A new cancer resulting from treatment of earlier cancer 


 
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Possible Side Effects of Avelumab  
(Table Version Date: April 23, 2019) 
 
Special Precautions 
Side effects of avelumab may happen anytime during treatment or even after your treatment 
has ended.  Some of these problems may happen more often when avelumab is used in 
combination with talazoparib.  Call or see your healthcare provider right away if you 
develop any problems listed below or the symptoms get worse. 
 
 
COMMON, SOME MAY BE SERIOUS 
In 100 people receiving AVELUMAB, more than 20 and up to 100 may have: 
• Tiredness 
 
OCCASIONAL, SOME MAY BE SERIOUS   
In 100 people receiving AVELUMAB, from 4 to 20 may have: 
• Anemia which may require blood transfusion 
• Diarrhea, nausea, vomiting 
• Chills, fever 
• Flu-like symptoms including body aches 
• Infection 
• Reaction during or following a drug infusion which may cause fever, chills, rash, low 
blood pressure 
• Bruising, bleeding 
• Loss of appetite 
• Cough 
• Dry skin 
• Itching, acne, rash 
 
Avelumab may cause your immune system to attack normal organs and cause side effects in 
many parts of the body. These problems may include but are not limited to: 
 
• Hormone gland problems (especially the thyroid, pituitary and adrenal glands, and 
pancreas).  Signs and symptoms may include: headaches that will not go away or 
unusual headaches, extreme tiredness or changes in mood or behavior decreased sex 
drive; weight loss or weight gain; excessive thirst or urine; dizziness or fainting  
• Damage to the pancreas which may cause belly pain and hospitalization  
• Pain or swelling of the joints 
• Problem of the muscle (myositis), which can cause muscle pain and severe muscle 
weakness sometimes with dark urine 
 


 
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RARE, AND SERIOUS   
In 100 people receiving AVELUMAB, 3 or fewer may have: 
Avelumab may cause your immune system to attack normal organs and cause side effects in 
many parts of the body. These problems may include but are not limited to: 
 
• Heart problems including inflammation and heart failure.  Symptoms and signs of 
heart problem may include: Shortness of breath, swelling of the ankle and body 
• Swelling and redness of the eye 
• Intestinal problems (colitis) that can rarely lead to tears or holes in your intestine. 
Signs and symptoms of colitis may include: diarrhea or increase in bowel movements, 
blood in your stools or dark, tarry, sticky stools, severe belly pain or tenderness 
• Liver problems (hepatitis) which can cause liver failure. Signs and symptoms of 
hepatitis may include: yellowing of your skin or the whites of your eyes, severe 
nausea or vomiting; drowsiness; pain in the right upper belly 
• A condition with high blood sugar (diabetes) which leads to tiredness, frequent 
urination or excessive thirst which may require treatment with insulin 
• Problem of the nerves that can cause paralysis.  Signs and symptoms may include: 
numbness, tingling of hands and feet; weakness of the arms, legs and facial muscle 
movement 
• Inflammation of the brain (meningitis/encephalitis), which may cause: headache, 
confusion, sleepiness, seizures, and stiff neck 
• Kidney problems, including nephritis and kidney failure requiring dialysis.  Signs of 
kidney problems may include: decrease in the amount of urine, blood in your urine, 
ankle swelling 
• Lung problems (pneumonitis and pleural effusion). Symptoms may include: new or 
worsening cough, chest pain, shortness of breath 
 
Additional Drug Risks 
 
Drug Interactions 
 
Over the counter, herbal medicines and other prescribed drugs will be reviewed by the study 
team for potential drug interactions. Your doctor or a member of the study team will tell you if 
you need to stop, modify or change any of these medicines or drugs before you start taking 
talazoparib and avelumab.  
 
Any medications or substances that contain strong P-gp or BCRP inhibitors should be avoided 
while you are taking talazoparib. Caution should be used for coadministration of other P-gp 
inhibitors (e.g., amiodarone, azithromycin, captopril, carvedilol, clarithromycin, conivaptan, 
cyclosporine, diltiazem, erythromycin, felodipine, lopinavir, quercetin), P-gp inducers (e.g., 
avasimibe, carbamazepine, phenytoin, St John’s wort), or BCRP inhibitors (e.g., cyclosporine, 
eltrombopag, and gefitinib).  
 
Throughout your treatment, you should inform your doctor about any medication changes. 


 
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Do not receive any live attenuated vaccinations, such as shingles or influenza nasal spray, while 
you are taking part in this study.  
 
Rarely, there are problems getting enough supplies of the study drugs. If that happens, your 
doctor will talk with you about your options. 
 
What are my responsibilities in this study? 
 
If you choose to take part in this study you will need to: 
 
• Keep your study appointments. 
• Tell your doctor about: 
o all medications and supplements you are taking 
o any side effects  
o any doctors’ visits or hospital stays outside of this study  
o and if you have been or are currently in another research study. 
• Write down in your patient diary when you take the study drug talazoparib.  
 
For women: Do not get pregnant or breastfeed while taking part in this study. You must 
continue to use your approved method of birth control during the study and for 7 months after 
last dose. Tell your study doctor right away if you think that you have become pregnant during 
the study or within 7 months after your last dose of study treatment.  
 
For men: Do not father a baby while taking part in this study. You must continue to use your 
approved method of birth control during the study and for 4 months after last dose. Do not 
donate sperm while taking part in this study and for 4 months after your last dose of study 
treatment.  Tell your study doctor right away if you think that your partner has become pregnant 
during the study or within 4 months after your last dose of study treatment. 
 
What are the costs of taking part in this study? 
 
You and/or your insurance plan will need to pay for the costs of medical care you get as part of 
the study, just as you would if you were getting the usual care for your cancer.  This includes: 
 
• 
the costs of tests, exams, procedures, and drugs that you get during the study to 
monitor your safety and prevent and treat side effects.   
• 
the costs of getting the talazoparib and avelumab ready and giving it to you. 
• 
your insurance co-pays and deductibles. 
 
Talk to your insurance provider and make sure that you understand what your insurance pays for 
and what it doesn’t pay for if you take part in this clinical trial.  Also, find out if you need 
approval from your plan before you can take part in the study.  
 


 
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Ask your doctor or nurse for help finding the right person to talk to if you are unsure which costs 
will be billed to you or your insurance provider.  
 
You or your insurance provider will not have to pay for the study drugs talazoparib and 
avelumab, exams, tests, and procedures done for research purposes only or that are covered by 
the study. These include: 
 
• the study drugs talazoparib and avelumab. 
• the collection or testing of the circulating tumor DNA before you begin the study, on 
Cycle 3 Day 1, if your disease becomes worse, and when you stop study treatment 
 
Taking part in this study may mean that you need to make more visits to the clinic or hospital 
than if you were getting the usual approach to treat your cancer.  You may: 
 
• Have more travel costs. 
• Need to take more time off work. 
• Have other additional personal costs. 
 
You will not be paid for taking part in this study.  The research may lead to new tests, drugs, or 
other products for sale.  If it does, you will not get any payment.   
 
What happens if I am injured because I took part in this study? 
 
If you are injured as a result of taking part in this study and need medical treatment, please talk 
with your study doctor right away about your treatment options.  The study sponsors will not pay 
for medical treatment for injury.  Your insurance company may not be willing to pay for a study-
related injury.  Ask them if they will pay.  If you do not have insurance, then you would need to 
pay for these medical costs. 
 
If you feel this injury was caused by medical error on the part of the study doctors or others 
involved in the study, you have the legal right to seek payment, even though you are in a study.  
Agreeing to take part in this study does not mean you give up these rights. 
 
Who will see my medical information? 
 
Your privacy is very important to us.  The study doctors will make every effort to protect it.  The 
study doctors have a privacy permit to help protect your records if there is a court case.  
However, some of your medical information may be given out if required by law.  If this should 
happen, the study doctors will do their best to make sure that any information that goes out to 
others will not identify who you are.  
 
Some of your health information, such as your response to cancer treatment, results of study 
tests, and medicines you took, will be kept by the study sponsor in a central research database.  
However, your name and contact information will not be put in the database.  If information 


 
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from this study is published or presented at scientific meetings, your name and other personal 
information will not be used.  
 
There are organizations that may look at or receive copies of some of the information in your 
study records.  Your health information in the research database also may be shared with these 
organizations.  They must keep your information private, unless required by law to give it to 
another group.   
 
Some of these organizations are: 
 
• The study sponsor, SWOG Cancer Research Network, and any company supporting the 
study now or in the future. This would include any organization helping the company 
with the study.  
• The National Cancer Institute Central Institutional Review Board (NCI CIRB) which is a 
group of people who review the research with the goal of protecting the people who take 
part in the study. 
• The Food and Drug Administration (FDA) and the groups it works with to review 
research.   
• The National Cancer Institute (NCI) and the groups it works with to review research. 
• The NCI’s National Clinical Trials Network and the groups it works with to conduct 
research. 
• Transmission of Imaging and Data (TRIAD) and Imaging and Radiation Oncology Core 
(IROC)-Your medical images with clinical study data (e.g., the treatment Group you are 
assigned to, etc.) will be transferred using a computer program called TRIAD to IROC, a 
central imaging laboratory sponsored by the NCI and located at Ohio State University in 
Columbus, Ohio.  Your medical images will be reviewed by physicians at this 
organization as part of the study analysis for this trial.    
 
In addition to storing data in the study database, data from studies that are publicly funded may 
also be shared broadly for future research with protections for your privacy. The goal of this data 
sharing is to make more research possible that may improve people’s health. Your study records 
may be stored and shared for future use in public databases.  However, your name and other 
personal information will not be used.   
 
Some types of future research may include looking at your information and information from 
other patients to see who had side effects across many studies or comparing new study data with 
older study data.  However, right now we don’t know what research may be done in the future 
using your information.  This means that: 
 
• You will not be asked if you agree to take part in the specific future research studies 
using your health information.   
• You and your study doctor will not be told when or what type of research will be done. 
• You will not get reports or other information about any research that is done using your 
information.  
 


 
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There are laws that protect your genetic information.  However, there is a risk that someone 
could get access to your genetic information and identify you by name.  In some cases, 
employers could use your genetic information to decide whether to hire or fire you.  The study 
doctors believe the risk of this happening is very small.  However, the risk may increase in the 
future as people find new ways of tracing information.  For more information about the laws that 
protect you, ask your study doctor. 
 
Where can I get more information?   
 
You may visit the NCI web site at http://cancer.gov/ for more information about studies or 
general information about cancer.  You may also call the NCI Cancer Information Service to get 
the same information at: 1-800-4-CANCER (1-800-422-6237). 
 
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required 
by U.S. Law.  This Web site will not include information that can identify you.  At most, the 
Web site will include a summary of the results.  You can search this Web site at any time. 
 
You can talk to the study doctor about any questions or concerns you have about this study or to 
report side effects or injuries.  Contact the study doctor __________________ (insert name of 
study doctor[s]) at __________________ (insert telephone number). 
 
For questions about your rights while in this study, call the __________________ (insert name 
of organization or center) Institutional Review Board at __________________ (insert telephone 
number).  
 
Optional studies that you can choose to take part in 
 
This part of the consent form is about optional studies that you can choose to take part in.  They 
are separate from the main study described above.  These optional studies will not benefit your 
health.  The researchers leading these optional studies hope the results will help other people 
with cancer in the future. The results will not be added to your medical records and you or your 
study doctor will not know the results. 
 
Taking part in these optional studies is your choice.  You can still take part in the main study 
even if you say “no” to any or all of these studies. There is no penalty for saying “no.” You and 
your insurance company will not be billed for these optional studies.  If you sign up for, but 
cannot complete any of these studies for any reason, you can still take part in the main study. 
 
Circle your choice of “yes” or “no” for each of the following studies. 
 
 
 


 
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Future contact 
I agree that my study doctor, or someone on the study team, may contact me or my doctor 
to see if I wish to participate in other research in the future.  
Yes 
No 
 
Optional sample collections for known laboratory studies and/or storage for possible 
future studies 
 
Researchers are trying to learn more about cancer and other health problems using blood and 
tissue samples from people who take part in clinical trials.  By studying these samples, 
researchers hope to find new ways to prevent, detect, treat, or cure diseases. 
 
Some of these studies may be about how genes affect health and disease.  Other studies may look 
at how genes affect a person’s response to treatment.  Genes carry information about traits that 
are found in you and your family.  Examples of traits are the color of your eyes, having curly or 
straight hair, and certain health conditions that are passed down in families.  Some of the studies 
may lead to new products, such as drugs or tests for diseases. 
 
Unknown future studies 
 
If you choose to take part in this optional study, your samples will be collected and stored.  
Storing samples for future studies is called “biobanking.”  The biobank is being run by SWOG 
Cancer Research Network and is supported by the NCI.  This is a publicly funded study. Samples 
from publicly funded studies are required to be shared as broadly as possible. However, we will 
protect your privacy. The goal of this is to make more research possible that may improve 
people’s health. Also, any health-related information, such as your response to cancer treatment, 
results of study tests, and medicines you took, will be stored for future use. 
 
The biobank is a public research resource. It has controlled access. This means that researchers 
who want to get samples and data from it must submit a specific research request. The request 
identifies who they are and what their planned research project is. Before getting the samples and 
data, researchers must agree to keep the data private, only use it for their planned research 
project, and never use it to try to identify you.   
 
Right now, we don’t know what research may be done in the future using your blood samples.   
 
This means that: 
 
• You will not be asked if you agree to take part in the future research studies.   
• You and your study doctor will not be told when or what type of research will be done. 
• You will not get reports or other information about any research that is done using your 
samples.  


 
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Unknown future research studies may include sequencing of all or part of your DNA. This is 
called genomic sequencing. Sequencing allows researchers to identify your genetic code. 
Changes in your genetic code may be passed down through your family. For example, these 
genetic changes may be passed down to your children in the same way that eye and hair color are 
passed down. These are called germline changes. 
 
 
What is involved in this optional sample collection? 
 
If you agree to take part, here is what will happen next: 
 
1. About 2 teaspoons of blood will be collected from a vein in your arm (at the same time as 
other study blood tests) before you begin treatment, on Cycles 2, 3, 4, and again if your 
cancer gets worse.  
2. Your samples will be stored in the biobank.  There is no limit on the length of time we 
will keep your samples and research information.  The samples will be kept until they are 
used for research or destroyed. 
3. Researchers can only get samples from the biobank after their research has been 
approved by experts.  Researchers will not be given your name or contact information.   
4. Some of your genetic and health information may be placed in central databases for 
researchers to use.  The databases will not include your name or contact information.   
 
What are the risks in this optional sample collection? 
 
1. The most common risks related to drawing blood from your arm are brief pain and maybe 
a bruise.   
2. Generally, hospitals will keep some of your tissue. This tissue may be used to help treat 
cancer in the future.  There is a small risk that when this tissue sample is submitted to the 
biobank for this optional sample collection, your tissue could be used up.    
3. Your medical and genetic information is unique to you.  There is a risk that someone 
outside of the research study could get access to your study records or trace information 
in a database back to you.  They could use that information in a way that could harm you.  
Researchers believe the chance that someone could access and misuse your information is 
very small.  However, the risk may increase in the future as people find new ways of 
tracing information.  
4. In some cases, this information could be used to make it harder for you to get or keep a 
job and get or keep health insurance.  There are laws against the misuse of genetic 
information, but they may not give full protection. For more information about the laws 
that protect you, ask your study doctor or visit:  https://www.genome.gov/10002328/  
 
How will information about me be kept private? 
 
Your privacy is very important to the study researchers and biobank.  They will make every 
effort to protect it.  Here are just a few of the steps they will take: 
 


 
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1. They will remove identifiers, such as your initials, from your sample and information.   
They will replace them with a code number.  There will be a master list linking the code 
numbers to names, but they will keep it separate from the samples and information. 
2. Researchers who study your sample and information will not know who you are.   They 
also must agree that they will not try to find out who you are. 
3. Your personal information will not be given to anyone unless it is required by law.  
4. If research results are published, your name and other personal information will not be 
used. 
 
What are the benefits to taking part in this optional sample collection? 
 
You will not benefit from taking part.  
 
The researchers, using the samples from you and others, might make discoveries that could help 
people in the future. 
 
Are there any costs or payments to this optional sample collection? 
 
There are no costs to you or your insurance.  You will not be paid for taking part in this study.  
The research may lead to new tests, drugs, or other products for sale.  If it does, you will not get 
any payment. 
 
What if I change my mind about this optional sample collection? 
 
If you decide you no longer want your samples to be used, you can call the study doctor, 
______________________ (insert name of study doctor for main trial) at __________________ 
(insert telephone number of study doctor for main trial), who will let the biobank know.  Then, 
any sample that remains in the biobank will be destroyed or returned to your study doctor.  This 
will not apply to any samples or related health information that have already been given to or 
used by researchers. 
 
What if I have questions about this optional sample collection? 
 
If you have questions about the use of your samples for research, contact the study doctor, 
______________________ (insert name of study doctor for main trial) at __________________ 
(insert telephone number of study doctor for main trial). 
 
Please circle your answer below to show if you would or would not like to take part in each 
optional study: 
 
Samples for unknown future studies: 
 
1. 
I agree that my samples and related health information may be kept in a biobank 
for use in future health research. 
 
YES 
 
NO 
This is the end of the section about optional studies. 


 
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My signature agreeing to take part in the study 
 
I have read this consent form or had it read to me.  I have discussed it with the study doctor and 
my questions have been answered.  I will be given a signed and dated copy of this form.  I agree 
to take part in the main study.  I also agree to take part in any additional studies where I circled 
“yes”. 
 
Participant’s signature (or legally authorized representative) 
 
_____________________________________________________________________________ 
 
Date of signature   ______________________________________________________________ 
 
Signature of person(s) conducting the informed consent discussion 
 
_____________________________________________________________________________  
 
Date of signature   ______________________________________________________________