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e. expedited reporting for investigational

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

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 CTEPAERS within the timeframes detailed in the table below.  
| Hospitalization               | Grade 1          | Timeframes       | Grade 3 Timeframes   | Grade 4 & 5   |
|-------------------------------|------------------|------------------|----------------------|---------------|
| Grade 2                       |                  |                  |                      |               |
| Timeframes                    | Timeframes       |                  |                      |               |
| Resulting in  Hospitalization | 10 Calendar Days |                  |                      |               |
| ≥ 24 hrs                      | 24-Hour 5        |                  |                      |               |
| Not resulting in              | Calendar Days    |                  |                      |               |
| Hospitalization               | Not required     | 10 Calendar Days |                      |               |
| ≥ 24 hrs                      |                  |                  |                      |               |  
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 24hour 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

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
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g. reporting secondary malignancy including

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

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 CTEPAERS 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.  
| Cycle Length = 28 days (+/- 3 days)                                       | At Off                                                        | Off Tx FU Prior                          | Off Tx FU After   |                     |    |     |     |     |
|---------------------------------------------------------------------------|---------------------------------------------------------------|------------------------------------------|-------------------|---------------------|----|-----|-----|-----|
| Tx                                                                        | to Prog                                                       | Prog 2                                   |                   |                     |    |     |     |     |
| REQUIRED  STUDIES                                                         | Cycle 1                                                       | Cycle 2                                  | Cycle 3           | Subsequent Cycles 1 |    |     |     |     |
| Pre-Reg (w/in 28 days  prior to  registration,  unless  otherwise  noted) |                                                               |                                          |                   |                     |    |     |     |     |
| 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 | Results up to 48 hours prior to Day 1 tx |                   |                     |    |     |     |     |
| repeated on C1D1.                                                         |                                                               |                                          |                   |                     |    |     |     |     |
| 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                                                      | X 14                                                          |                                          |                   |                     |    |     |     |     |
| load test                                                                 |                                                               |                                          |                   |                     |    |     |     |     |  
| Cycle Length = 28 days (+/- 3 days)                                       | At Off        | Off Tx FU Prior   | Off Tx FU After  Prog 2   |                     |
|---------------------------------------------------------------------------|---------------|-------------------|---------------------------|---------------------|
| REQUIRED                                                                  | Tx            | to Prog           |                           |                     |
| STUDIES                                                                   | Cycle 1       | Cycle 2           | Cycle 3                   | Subsequent Cycles 1 |
| Pre-Reg (w/in 28 days  prior to  registration,  unless  otherwise  noted) |               |                   |                           |                     |
| HIV viral load test                                                       | X 14          |                   |                           |                     |
| X-RAYS & SCANS CT or MRI for                                              | X 4           | X 4               | X 4                       |                     |
| Disease                                                                   | Week 12       | X 4               | X 4                       |                     |
| Week 6                                                                    |               |                   |                           |                     |
| Assessment 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             | X                 | X                         | X                   |
| Days 1-28                                                                 | Days 1-28     | Days 1-28         | Days 1-28                 |                     |
| Avelumab 12                                                               | X             | X                 | X                         | X                   |
| Days 1, 15                                                                | Days 1, 15    | Days 1, 15        | Days 1, 15                |                     |  
NOTE: Forms are found on the CTSU website (www.ctsu.org). Forms submission guidelines are found in Section 14.0.  
  
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.
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footnotes for calendar 9.1 (talazoparib

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

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.
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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.
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 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.
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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 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.  
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 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.  
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.  
Patients will be graded according to the Zubrod Performance Status Scale.
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point description

10.5 Time to Death  
| 0   | Fully active, able to carry on all pre-disease performance without  restriction.   |
|-----|------------------------------------------------------------------------------------|  
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)  
| 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.                                                                        |  
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.
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11.0 statistical considerations 11.1 sample

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 (nonsynonymous 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   |
|-----------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|  
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 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.
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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  
| 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:  
Table 3: Criteria for interpretation of study data **at final analysis**  
| Disease Control at 12 weeks evaluation   |                         |                         |
|------------------------------------------|-------------------------|-------------------------|
| Response 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    |  
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.
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12.0 discipline review 12.1 radiology

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.
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13.0 registration guidelines see section

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 substudy registration.  
  
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.
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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.
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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  
- 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 CTEPIAM 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. 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
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a. within 15 days of

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
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b. if patient consents submit

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  
  
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.
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d. within 15 days after

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.
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f. within 30 days once

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).
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g. within 15 days of

Vital Status Form Site(s) of Progression or Relapse Form  
  
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.
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h. within 30 days of

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.
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i. data submission for patients

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.
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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  
  
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-AMCPRO-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 CellFree 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.
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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.  
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 43-99̊F (6-37̊C).  
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*)
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/biospecimenresources/biospecimen-processing-and-submission-procedures).  
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.
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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**.
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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, electronic submission of imaging.
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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.
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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 TRIADSupport@acr.org or 1-703-390-9858.
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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.
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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.
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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).
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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  
  
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 MultiParty 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.  
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 nonCooperative 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:
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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.
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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.
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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.
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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.
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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.  
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.  
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 stressinducible 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 platinumtreated 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).
schema
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  
  
  
| 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.                                                                |                    |                     |                   |  
18.1 New York Heart Association Classification  
  
18.2 Monitoring Plan For information on the **LUNGMAP** Monitoring Plan, please refer to **LUNGMAP** Appendix 18.2.  
18.3 Instructions for the SWOG Biospecimen Bank
schema
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.
schema
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.  
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.
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.  
| Talazoparib capsules are to be stored at controlled room temperature, 59-86°F. Date Was dose taken? What time?   | Comments                         |       |                 |                 |
|------------------------------------------------------------------------------------------------------------------|----------------------------------|-------|-----------------|-----------------|
| If you have questions, contact: _________________________                                                        | Telephone: _____________________ |       |                 |                 |
| 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 |                 |  
Page 83 Version Date 4/7/21  
| 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   |  
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  
   
Diagnosis: Trial \#:  
| 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.
schema
to the patient take this

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.
schema
these are the things that

- 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.
schema
these are the things that

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 _____________________________________.  
  
Page 85 Version Date 4/7/21 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:                                                                                                                 | Your healthcare providers should be aware of any medicines that are |                                      |
| Diagnosis:                                                                                                                                              | considered strong inhibitors of P-gp and BCRP.                                                                                                                          |                                                                     |                                      |
| Study Doctor: Study Doctor Phone #: NCI Trial #:                                                                                                        | Before prescribing new medicines, your health care provider should                                                                                                      |                                                                     |                                      |
| Study Drug(S):                                                                                                                                          | check a frequently-updated medical reference for a list of drugs to  avoid or contact your study doctor.                                                                |                                                                     |                                      |
| Talazoparib may interact with  drugs that use certain transport  proteins in your body.  Avoid any medicines that are  considered strong inhibitors of Pgp and BCRP while taking  talazoparib.                                                                                                                                                         |                                                                                                                                                                         | 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      |  
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                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                            | Date: <dd-Mmm-yyyy> |
| Last Name / Title (Printed)>  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  <dd-Mmm-yyyy> applicable Distribution and/or IRT System  Used to Distribute and/or Dispense  investigational product (N/A for PCH) Storage Condition on Label |                     |  
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)   |
|-------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------|