Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors

• ClinicalTrials.gov Identifier: NCT03565991
• Recruitment Status: Terminated
• First Posted: June 21, 2018
• Results First Posted: August 7, 2023
• Last Update Posted: September 25, 2023
• Sponsor: Pfizer
• Information provided by (Responsible Party): Pfizer

Tracking Information

• First Submitted Date: May 25, 2018
• First Posted Date: June 21, 2018
• Results First Submitted Date: March 22, 2023
• Results First Posted Date: August 7, 2023
• Last Update Posted Date: September 25, 2023
• Actual Study Start Date: June 18, 2018
• Actual Primary Completion Date: March 28, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 22, 2023)

Percentage of Participants With Confirmed Objective Response (OR) as Assessed by Blinded Independent Central Review (BICR) [ Time Frame: From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever came first, assessed up to approximately 24 months ]

For participants with solid tumors, except metastatic Castration Resistant Prostate Cancer (mCRPC), OR was defined as a complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1), both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per Prostate Cancer Working Group 3 (PCWG3) criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-Progressive Disease (PD), where PD was unequivocal progression of pre-existing lesions.

Original Primary Outcome Measures (submitted: June 11, 2018)

Confirmed Objective Response (OR) [ Time Frame: From date of first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months ]

Confirmed OR in patients with locally advanced or metastatic solid tumors with BRCA 1/2 or ATM defect, as assessed by Blinded Independent Central Review using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1. and PCWG3.

Current Secondary Outcome Measures (submitted: August 31, 2023)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [ Time Frame: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately ]
  An adverse event (AE) was any untoward medical occurrence in a clinical investigation where participants administered a product or medical device. TEAEs were those events with onset dates occurring during the on-treatment period. A Serious Adverse Event (SAE) was any untoward medical occurrence at any dose that: resulted in death, was life threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, or resulted in congenital anomaly/birth defect. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. TEAEs were graded by the investigator using National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) v4.03 as Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE.
• Number of Participants With New or Worsening Hematology Laboratory Test Results During the On-Treatment Period [ Time Frame: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately ]
  The laboratory results were graded according to the CTCAE v4.03 severity grade whenever applicable. Laboratory test abnormalities were summarized according to worst toxicity grade observed for each laboratory test. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).
• Number of Participants With New or Worsening Chemistry Laboratory Test Results During the On-Treatment Period [ Time Frame: From baseline up to 30 days after last dose of study treatment, maximum up to 4.3 years approximately ]
  The laboratory results were graded according to the CTCAE v4.03 severity grade whenever applicable. Laboratory test abnormalities were summarized according to worst toxicity grade observed for each laboratory test. As per NCI CTCAE toxicity grading v4.03, Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death related to AE. On-treatment period was defined as the time from the first dose of study treatment through minimum (30 days + last dose of study treatment, start day of new anti-cancer drug therapy - 1 day).
• Serum Lowest (Trough) Concentration (Ctrough) of Avelumab [ Time Frame: Predose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1 ]
  Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 0.2 mcg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented.
• Serum Maximum Concentration (Cmax) for Avelumab [ Time Frame: One hour post-dose on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1 ]
  Cmax was defined as maximum observed plasma concentration. The determination method of Cmax was observing directly from data.
• Plasma Ctrough for Talazoparib [ Time Frame: Predose on Cycle 1 Days 1, 15 and Cycle 3 Day 1 ]
  Ctrough was defined as predose concentration during multiple dosing. The determination method of Ctrough was observing directly from data. The lower limit of quantification (LLQ) was 25 pg/mL. For Cycle 1 Day 1, as the number of observations above lower limit of quantification (NALQ) = 0, summary statistics were not presented. Evaluable participants were participants with non-missing Ctrough concentrations at each specific time point and meeting 2 conditions: participants received 14 consecutive days of talazoparib dose without dosing interruption prior to sample collection (except on Cycle 1 Day 1) and sample collection within 24 hours ± 10% (2 hours and 24 minutes) after the previous day's dose and no more than 5 minutes (0.083 hours) after the administration of the dose on the day of PK sample collection. Predose PK samples on Cycle 1 Day 1 must have been collected prior to dose.
• Plasma Post-dose Concentrations for Talazoparib [ Time Frame: Postdose (samples collected within 2 hours post dose plus/minus 12 minutes) on Days 1,15 of Cycle 1, and Day 1 of Cycle 3 ]
  In this OM, the post-dose concentrations for talazoparib in plasma were reported.
• Number of Participants by Avelumab Anti-drug Antibody (ADA) Categories [ Time Frame: Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1 ]
  Blood samples were assayed for ADA using a validated assay. ADA never-positive = no positive ADA results at any time point. ADA ever-positive =at least one positive ADA result at any time point. Baseline ADA positive =a positive ADA result at baseline. Treatment-boosted ADA =a positive ADA result at baseline and the titer >=8×baseline titer at least once after treatment with avelumab. Treatment-induced ADA = participant was ADA-negative at baseline and had at least one positive post-baseline ADA result; or the participant had at least one positive post-baseline ADA result if no baseline sample. Transient ADA response = participants with treatment-induced ADA had (a single positive ADA result or duration between first and last positive result <16 weeks) and ADA result at the last assessment was not positive. Persistent ADA response =participants with treatment-induced ADA had duration between first and last positive ADA result >=16 weeks or a positive ADA result at the last assessment.
• Number of Participants With Neutralizing Antibodies (Nab) Levels Against Avelumab Ever-Positive [ Time Frame: Predose (within 2 hours before start of avelumab infusion) on Day 1 of Cycles 1, 3, 6, 12, 18, 24 and Day 15 of Cycle 1 ]
  Nab ever-positive was defined as at least one positive Nab result at any time point. Samples positive for ADA with persistent treatment-induced ADA response could be analyzed for Nab.
• Percentage of Participants With Confirmed OR as Assessed by The Investigator [ Time Frame: From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months ]
  For participants with solid tumors, except mCRPC, OR was defined as a CR or PR per RECIST v1.1, both confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. For participants with mCRPC, OR was defined as the percentage of participants with a best overall soft tissue response of CR or PR per RECIST v1.1 with no evidence of confirmed bone disease progression per PCWG3 criteria. Per RECIST v1.1, CR was defined as complete disappearance of all target and non-target lesions with the exception of nodal disease. PR was defined as greater than or equal to 30% decrease under baseline of the sum of diameters of all target measurable lesions. Non-target PR lesions must be non-PD, where PD was unequivocal progression of pre-existing lesions.
• Time to Tumor Response (TTR) as Assessed by BICR [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a Best Overall Response (BOR) of CR or PR per RECIST v1.1.
• TTR as Assessed by Investigator [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: TTR was defined for participants with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response. For participants with mCRPC: TTR was defined as the time from the first dose of study treatment to the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression on bone scan per PCWG3. Soft tissue response was defined as a BOR of CR or PR per RECIST v1.1.
• Duration of Response (DoR) as Assessed by BICR [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occured first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occured first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.
• DoR as Assessed by Investigator [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurred first. For participants with mCRPC: DoR was defined for participants with confirmed objective response (CR or PR) as the time from the first objective evidence of soft tissue response (subsequently confirmed) per RECIST v1.1 and no evidence of confirmed bone disease progression by PCWG3 to the first subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first. Radiographic progression was defined as soft tissue progression evaluated per RECIST v1.1 or bone disease progression evaluated per PCWG3.
• Progression Free Survival (PFS) as Assessed by BICR [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.
• PFS as Assessed by Investigator [ Time Frame: Baseline up to approximately 24 months ]
  For participants with solid tumors, except mCRPC: PFS was defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurred first. For participants with mCRPC: PFS was defined as the time from the first dose of study treatment to documentation of radiographic progression in soft tissue evaluated per RECIST v1.1, in bone evaluated per PCWG3, or death, whichever occurred first.
• Overall Survival (OS) for All Participants [ Time Frame: Baseline up to approximately 24 months ]
  OS was defined as the time from the first dose of study treatment to the date of death. Participants without an event (death) were censored at the date of last contact.
• Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC [ Time Frame: Baseline up to approximately 24 months ]
  For participants with mCRPC, time to PSA progression was defined as the time from the first dose to the date that a >=25% increase in PSA with an absolute increase of >=2 μg/L (2 ng/mL) above the nadir (or baseline for participants with no PSA decline) was documented, confirmed by a second consecutive PSA value obtained >=3 weeks (21 days) later.
• Number of Participants With Confirmed PSA Response [ Time Frame: Baseline up to approximately 24 months ]
  For participants with mCRPC, PSA response was defined as confirmed PSA decline >=50% compared to baseline. PSA response was calculated as a decline from baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50%. A PSA response must have been confirmed by a second consecutive value at least 3 weeks later.
• Number of Participants With Circulating Tumor Cell (CTC) Count Conversion [ Time Frame: Day 1 of Cycle 1 to Cycle 4 ]
  For participants with mCRPC, CTC count conversion was defined as a decrease in CTC count from >=5 CTC per 7.5 mL of blood at baseline to <5 CTC per 7.5 mL of blood anytime on study.
• Number of Participants With Cancer Antigen 125 (CA-125) Response [ Time Frame: Baseline, Day 1 of each treatment Cycle, maximum up to 4.3 years approximately ]
  For participants with ovarian cancer, CA-125 response was defined as at least a 50% reduction in CA-125 levels from baseline. The response must have been confirmed and maintained for at least 28 days.
• Number of Participants With Positive Programmed Death Ligand 1 (PD-L1) Expression in Baseline Tumor Tissue [ Time Frame: Baseline ]
  PD-L1 expression on tumor and infiltrating immune cells was measured by immunohistochemistry (IHC). PD-L1 expression level was defined as the number of PD-L1 positive cells and/or qualitative assessment of PD-L1 staining on tumor and inflammatory cells in regions of interest. This OM reported the number of participants classified as positive according to scoring algorithms and cut-offs established from external sources.
• Number of Participants With Different Status for Defects in BRCA1, BRCA2 and ATM [ Time Frame: Baseline ]
  Participants were enrolled in the two cohorts based on BRCA 1/2 and ATM defect status assessed by the local laboratory. The participant BRCA and ATM status was assessed retrospectively by central laboratory, that may differ from the status assessed by the local laboratory. The ATM participants with a negative ATM status per the central laboratory were reported to have a positive ATM status per the local laboratory. Therefore, participants with negative ATM status might have been included in the ATM defect cohort. For defects in BRCA1, BRCA2 and ATM by central laboratory analysis, participants were classified as positive, negative, not analyzable or missing. The number of participants in each category of BRCA 1 defect, BRCA 2 defect, BRCA 1 or BRCA 2 defect and ATM defect were presented.
• Number of Participants by Status of Tumor Mutational Burden (TMB) at Baseline [ Time Frame: Baseline ]
  TMB was defined as the total number of mutations in the tumor genome, or number of mutations per megabase of DNA if derived from targeted sequencing. TMB categories were defined as high, low for a number of mutations per megabase >=10 and <10, respectively. The TMB category 'Not analyzable' included participants with available samples but not evaluable. The TMB category 'Missing' included participants with no sample available. The number of participants in each category at only baseline were tabulated.

Original Secondary Outcome Measures (submitted: June 11, 2018)

• Confirmed OR as assessed by the investigator [ Time Frame: From the first dose of study treatment until the date of first documented disease progression or date of death from any cause, whichever comes first, assessed up to approximately 24 months ]
  Confirmed OR as assessed by the investigator, using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1 and PCWG3.
• Time to tumor response (TTR) [ Time Frame: Baseline up to approximately 24 months ]
  TTR is defined for patients with confirmed objective response (CR or PR) as the time from the first dose of study treatment to the first documentation of objective tumor response.
• Duration of response (DR) [ Time Frame: Baseline up to approximately 24 months ]
  DR is defined for patients with confirmed objective response (CR or PR) as the time from the first documentation of objective tumor response to the first documentation of objective tumor progression or to death due to any cause, whichever occurs first.
• Progression free survival (PFS) [ Time Frame: Baseline up to approximately 24 months ]
  PFS is defined as the time from the first dose of study treatment to the date of disease progression by RECIST v1.1 or death due to any cause, whichever occurs first.
• Overall survival (OS) [ Time Frame: Baseline up to approximately 24 months ]
  OS is defined as the time from the first dose of study treatment to the date of death.
• Time to prostate-specific antigen (PSA) progression for mCRPC patients [ Time Frame: Baseline up to approximately 24 months ]
  Time to PSA progression is defined as the time from the first dose to the date that a greater than or equal to 25% increase in PSA from baseline.
• CA-125 response for ovarian cancer patients [ Time Frame: Baseline and Day 1 of each Cycle (1 cycle is 28 days) ]
  CA-125 response is defined as at least a 50% reduction in CA-125 levels from baseline.
• Prostate specific antigen (PSA) response [ Time Frame: Baseline up to approximately 24 months ]
  PSA response is defined as at least a 50% reduction in PSA levels from baseline
• Circulating Tumor Cells (CTC) count conversion for mCRPC patients [ Time Frame: Day 1 Cycles 1-4 ]
  CTC conversion for mCRPC patients
• Biomarker PD-L1 [ Time Frame: Baseline ]
  PD-L1 expression level in baseline tumor tissue.
• Presence of defects in a panel of key oncogenes [ Time Frame: Baseline. ]
  Presence of defects in a panel of key oncogenes.
• Plasma concentrations Ctrough talazoparib [ Time Frame: Day 1, Day 15 Cycle 3 ]
  Pharmacokinetic parameter for talazoparib.
• Plasma concentrations post-dose talazoparib [ Time Frame: Day 1, Day 15 Cycle 3 ]
  Pharmacokinetic parameter for talazoparib.
• Serum concentrations Ctrough avelumab [ Time Frame: Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1 ]
  Pharmacokinetic parameter for avelumab.
• Serum concentrations Cmax avelumab [ Time Frame: Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1 ]
  Pharmacokinetic parameter for avelumab.
• Anti-drug antibody (ADA) levels of avelumab [ Time Frame: Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1 ]
  Immunogenicity assessment of avelumab.
• Neurtralizing antibodies (Nab) levels against avelumab [ Time Frame: Day 1 Cycles 1, 3, 6, 12, 18, 24 and Day 15 Cycle 1 ]
  Immunogenicity assessment of avelumab.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Javelin BRCA/ATM: Avelumab Plus Talazoparib in Patients With BRCA or ATM Mutant Solid Tumors
• Official Title: A PHASE 2 STUDY TO EVALUATE SAFETY AND ANTI-TUMOR ACTIVITY OF AVELUMAB IN COMBINATION WITH TALAZOPARIB IN PATIENTS WITH BRCA OR ATM MUTANT TUMORS JAVELIN BRCA/ATM
• Brief Summary: Avelumab in combination with talazoparib will be investigated in patients with locally advanced or metastatic solid tumors with a BRCA or ATM defect.

Detailed Description

Avelumab is a human immunoglobulin (Ig)G1 monoclonal antibody (mAb) directed against programmed death ligand 1 (PD-L1). Avelumab selectively binds to PD-L1 and competitively blocks its interaction with programmed death receptor 1 (PD-1), thereby interfering with this key immune checkpoint inhibition pathway. Avelumab is currently being investigated as single agent and in combination with other anti cancer therapies in patients with locally advanced or metastatic solid tumors and various hematological malignancies.

Talazoparib is a potent, orally bioavailable poly (adenosine diphosphate [ADP] ribose) polymerase (PARP) inhibitor, which is cytotoxic to human cancer cell lines harboring gene mutations that compromise deoxyribonucleic acid (DNA) repair, an effect referred to as synthetic lethality, and by trapping PARP protein on DNA thereby preventing DNA repair, replication, and transcription.

Avelumab in combination with talazoparib will be investigated in patients with locally advanced (primary or recurrent) or metastatic solid tumors with a BReast CAncer susceptibility gene (BRCA)1, or BRCA2, or ataxia telangiectasia mutated (ATM) gene defect.

• Study Type: Interventional
• Study Phase: Phase 2

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description:

Single arm study with two cohorts enrolled in parallel.

• Cohort 1 will enroll patients with locally advanced or metastatic solid tumors with one or more defects in the BRCA1 or BRCA2 genes
• Cohort 2 will enroll patients with locally advanced or metastatic solid tumors with one or more defects in the ATM gene

Masking: None (Open Label)
Masking Description:

Open label

Primary Purpose: Treatment

Condition

• Locally Advanced or Metastatic Solid Tumors
• Genes, BRCA 1

Intervention

• Drug: Avelumab
  IV treatment
  Other Name: Bavencio
• Drug: Talazoparib
  Oral treatment
  Other Name: MDV3800, BMN 673

Study Arms

Experimental: Combination of avelumab and talazoparib

Single arm open label

Interventions:

• Drug: Avelumab
• Drug: Talazoparib

• Publications *: Schram AM, Colombo N, Arrowsmith E, Narayan V, Yonemori K, Scambia G, Zelnak A, Bauer TM, Jin N, Ulahannan SV, Colleoni M, Aftimos P, Donoghue MTA, Rosen E, Rudneva VA, Telli ML, Domchek SM, Galsky MD, Hoyle M, Chappey C, Stewart R, Blake-Haskins JA, Yap TA. Avelumab Plus Talazoparib in Patients With BRCA1/2- or ATM-Altered Advanced Solid Tumors: Results From JAVELIN BRCA/ATM, an Open-Label, Multicenter, Phase 2b, Tumor-Agnostic Trial. JAMA Oncol. 2023 Jan 1;9(1):29-39. doi: 10.1001/jamaoncol.2022.5218. Erratum In: JAMA Oncol. 2023 Jul 1;9(7):1009.

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: June 22, 2020): 202
• Original Estimated Enrollment (submitted: June 11, 2018): 200
• Actual Study Completion Date: February 3, 2023
• Actual Primary Completion Date: March 28, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• BRCA1, BRCA2 and/or ATM gene defect.
• Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent
• Availability a tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy.
• Progressive disease at study enrollment.
• Minimum age 18 years (in Japan, minimum age 20 years).
• ECOG performance status 0 or 1.
• Adequate bone marrow, renal and liver function.
• For childbearing female patients, negative serum or urine pregnancy test at screening
• Signed and dated informed consent document.

Exclusion Criteria:

• Prior anti-cancer therapy or radiation therapy within 2 weeks prior to enrolment. Palliative radiotherapy to metastatic lesion(s) permitted providing that it has been completed at least 2 days prior to enrolment and no significant toxicity are expected.
• Major surgery within 4 weeks prior to study enrollment.
• Current use of immunosuppressive medication at the time of study enrollment.
• Known prior severe hypersensitivity to investigational products or any component in their formulations
• Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis.
• Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent.
• Prior organ transplantation including allogenic stem-cell transplantation.
• Administration of live attenuated vaccines within 4 weeks of study enrollment.
• Diagnosis of myelodysplastic syndrome.
• Known symptomatic brain metastases requiring steroids.
• Persisting toxicity related to prior therapy Grade >1.
• Known history of HIV or AIDS.
• Positive HBV or HCV test indicating acute or chronic infection.
• Active infection requiring systemic therapy.
• Clinically significant (active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study enrollment; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
• Diagnosis of any other malignancy within 2 years prior to study enrollment, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the breast, bladder, or cervix, or low-grade prostate cancer or other early-stage low-risk cancers.
• Pregnant or breastfeeding female patients; female or male patients who are able to have children who are unable or unwilling to use contraception as outlined in the protocol.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Belgium, Denmark, France, Italy, Japan, Netherlands, Spain, United Kingdom, United States

Administrative Information

• NCT Number: NCT03565991
• Other Study ID Numbers: B9991032; 2018-000345-39 ( EudraCT Number )
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
• URL: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests

• Current Responsible Party: Pfizer
• Original Responsible Party: Same as current
• Current Study Sponsor: Pfizer
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Pfizer CT.gov Call Center; Pfizer

• PRS Account: Pfizer
• Verification Date: August 2023