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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03330405




Registration number
NCT03330405
Ethics application status
Date submitted
16/10/2017
Date registered
6/11/2017

Titles & IDs
Public title
Javelin Parp Medley: Avelumab Plus Talazoparib In Locally Advanced Or Metastatic Solid Tumors
Scientific title
A PHASE 1B/2 STUDY TO EVALUATE SAFETY AND ANTI TUMOR ACTIVITY OF AVELUMAB IN COMBINATION WITH THE POLY(ADENOSINE DIPHOSPHATE [ADP]-RIBOSE) POLYMERASE (PARP) INHIBITOR TALAZOPARIB IN PATIENTS WITH LOCALLY ADVANCED OR METASTATIC SOLID TUMORS
Secondary ID [1] 0 0
2017-001509-33
Secondary ID [2] 0 0
B9991025
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Avelumab in Combination With Talazoparib Will be Investigated in Patients With Locally Advanced (Primary or Recurrent) or Metastatic Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Avelumab Phase 1b
Treatment: Drugs - Talazoparib Phase 1b
Treatment: Drugs - Avelumab Phase 2
Treatment: Drugs - Talazoparib Phase 2

Experimental: Dose Level 0 Phase 1b - Drug: Avelumab

Drug: Talazoparib

Experimental: Dose Level -1 Phase 1b - Drug: Avelumab

Drug: Talazoparib

Experimental: Dose Level -2 Phase 1b - Drug: Avelumab

Drug: Talazoparib

Experimental: A1. NSCLC Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: A2. NSCLC PD-L1 Resistant DDR+ Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: B1. TNBC Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: B2. HR+BC DDR Defect +Assay Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: C1. Ovarian CA Recurrent Plat-Sensitive Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: C2.Ovarian CA Recurrent Plat-Sensitive BRCA defect Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: D.Urothelial CA Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: E1. CRPC Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: E2. CRPC DDR Defect +Assay Phase 2 - Drug: Avelumab

Drug: Talazoparib

Experimental: F: Advanced Solid Tumors with BRCA or ATM defect Phase 2 - Drug: Avelumab

Drug: Talazoparib


Treatment: Drugs: Avelumab Phase 1b
Avelumab

Treatment: Drugs: Talazoparib Phase 1b
Talazoparib

Treatment: Drugs: Avelumab Phase 2
The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.

Treatment: Drugs: Talazoparib Phase 2
The dose will be determined after the overall available data (including safety and preliminary anti tumor activity) emerging from the Phase 1b portion of the study have been evaluated.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Cycle 1; 28 days
Primary outcome [2] 0 0
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 by Investigator Assessment
Timepoint [2] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
Primary outcome [3] 0 0
Phase 2: Percentage of Participants With Confirmed Objective Response (OR) as Per RECIST v1.1 and Prostate Cancer Working Group 3 (PCWG3) by Investigator Assessment
Timepoint [3] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 4.3 years approximately)
Secondary outcome [1] 0 0
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Timepoint [1] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [2] 0 0
Number of Participants With Grade >=3 TEAEs
Timepoint [2] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [3] 0 0
Number of Participants With Serious TEAEs
Timepoint [3] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [4] 0 0
Number of Participants With TEAEs Leading to Discontinuation of Either Study Drug
Timepoint [4] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [5] 0 0
Number of Participants With TEAEs Leading to Discontinuation of All Study Drugs
Timepoint [5] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [6] 0 0
Number of Participants With TEAEs Leading to Death
Timepoint [6] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [7] 0 0
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=1 During the On-Treatment Period
Timepoint [7] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [8] 0 0
Number of Participants With New or Worsening Hematology Laboratory Test Results to Grade >=3 During the On-Treatment Period
Timepoint [8] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [9] 0 0
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=1 During the On-Treatment Period
Timepoint [9] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [10] 0 0
Number of Participants With New or Worsening Chemistry Laboratory Test Results to Grade >=3 During the On-Treatment Period
Timepoint [10] 0 0
From start of the treatment up to 30 days after last dose or start of new anticancer therapy minus 1 day, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [11] 0 0
Trough Concentrations (Ctrough)/Predose and Maximum Concentrations (Cmax) of Serum Avelumab Concentrations (µg/mL) by Visit (Excluding Site 1055)
Timepoint [11] 0 0
Predose/0 Hour (H) and 1 H on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4, and additionally on Day 1 of Cycles 6, 9, 12, 18, and 24.
Secondary outcome [12] 0 0
Predose and Postdose Plasma Talazoparib Concentrations (pg/mL) by Visit (Excluding Site 1055)
Timepoint [12] 0 0
Pre-dose and post-dose (at the end of the avelumab infusion) on Days 1 and 15 of Cycle 1 and on Day 1 of Cycles 2-4.
Secondary outcome [13] 0 0
Number of Participants With at Least 1 Valid Anti-drug Antibody (ADA) Result at: Any Time Point (N0), Baseline (N1), Baseline and Post-Baseline (N2), and Post-Baseline and Without Positive Baseline ADA Result (N3)
Timepoint [13] 0 0
Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycle 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Secondary outcome [14] 0 0
Number of Participants by ADA Categories
Timepoint [14] 0 0
Pre-dose (within 2 hours of talazoparib dose) on Day 1 and Day 15 of Cycles 1, on Day 1 of Cycle 2-4 and then on Day 1 of Cycles 6, 9, 12, 18, 24, and at the end of treatment (EOT)
Secondary outcome [15] 0 0
Phase 1b: Percentage of Participants With Confirmed OR as Per RECIST v1.1 and PCWG3 by Investigator Assessment
Timepoint [15] 0 0
From start of the treatment until disease progression or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [16] 0 0
Phase 1b: Time to Response (TTR) in Participants With Confirmed CR or PR
Timepoint [16] 0 0
From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<=5.2 years approximately)
Secondary outcome [17] 0 0
Phase 2: TTR in Participants With Confirmed CR or PR
Timepoint [17] 0 0
From the first dose of study treatment to the first documentation of objective tumor response/the first objective evidence of soft tissue response with no evidence of confirmed bone disease progression (<= 5.2 years approximately)
Secondary outcome [18] 0 0
Phase 2: Duration of Response (DR) in Participants With Confirmed CR or PR
Timepoint [18] 0 0
From the first objective tumor response/soft tissue response to the first objective tumor progression/subsequent objective evidence of radiographic progression or death due to any cause, whichever occurred first (<=5.2 years approximately)
Secondary outcome [19] 0 0
Phase 1b: Progression-Free Survival (PFS) in Participants With Confirmed CR or PR
Timepoint [19] 0 0
From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [20] 0 0
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1)
Timepoint [20] 0 0
From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [21] 0 0
Phase 2: PFS in Participants With Confirmed CR or PR (RECIST v1.1 and PCWG3)
Timepoint [21] 0 0
From the first dose of study treatment to the date of disease progression/radiographic progression in soft tissue or bone, or death due to any cause, whichever occurred first (maximum up to 5.2 years approximately)
Secondary outcome [22] 0 0
Phase 2: Time to Prostate-Specific Antigen (PSA) Progression for Participants With mCRPC
Timepoint [22] 0 0
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 (maximum up to 5.2 years approximately)
Secondary outcome [23] 0 0
Phase 1b: Overall Survival
Timepoint [23] 0 0
From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Secondary outcome [24] 0 0
Phase 2: Overall Survival
Timepoint [24] 0 0
From the first dose of study treatment to the date of death (maximum up to 5.2 years approximately)
Secondary outcome [25] 0 0
Phase 2: Percentage of Participants With PSA Response
Timepoint [25] 0 0
From baseline PSA (ng/mL) to the maximal PSA response with a threshold of 50% (maximum up to 5.2 years approximately)
Secondary outcome [26] 0 0
Phase 1b: Percentage of Participants With CA-125 Response
Timepoint [26] 0 0
From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Secondary outcome [27] 0 0
Phase 2: Percentage of Participants With CA-125 Response
Timepoint [27] 0 0
From baseline to at least a 50% reduction in CA-125 level (maximum up to 5.2 years approximately)
Secondary outcome [28] 0 0
Number of Participants With Different Programmed Death-Ligand 1 (PD-L1) Status at Baseline
Timepoint [28] 0 0
At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Secondary outcome [29] 0 0
Number of Participants With Different Tumor Mutational Burden (TMB) at Baseline
Timepoint [29] 0 0
At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)
Secondary outcome [30] 0 0
Number of Participants With Different DNA Damage Repair (DDR) Status at Baseline
Timepoint [30] 0 0
At baseline (the last available assessment prior to the start of study treatment was defined as 'baseline' value or 'baseline' assessment)

Eligibility
Key inclusion criteria
* Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent in adult patients with: NSCLC, TNBC, HR+ breast cancer, recurrent platinum sensitive ovarian cancer, UC, CRPC, and other advanced solid tumors with a BRCA or ATM gene defect
* Mandatory primary or metastatic tumor biopsy. If archival tumor tissue is available from a biopsy/surgery the tumor tissue may be submitted without repeating a tumor biopsy during the screening period.
* Minimum age in Japan is 20 years.
* ECOG performance status 0 or 1.
* Resolved acute effects of prior therapy
* Adequate bone marrow, renal, and liver function.
* Negative serum pregnancy test at screening.
* Pregnant, breastfeeding females or female patients able to have children must agree to use highly effective method of contraception throughout the study and for at least 30 days after the last dose of avelumab and for at least 7 months after the last dose of talazoparib; fertile male patients must use a condom during treatment and for at least 4 months after the last dose of talazoparib.
* Signed and dated informed consent.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Prior treatment with a PARP inhibitor.
* Prior immunotherapy with IL-2, IFN-a, or an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, OX 40, GITR, LAG 3, IDO, TDO,TIM 3, CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways. Prior treatment with Sipuleucel-T for patients with mCRPC is allowed. For cohort A2 NSCLC patients prior treatment with anti-PD-1/L1 is allowed
* Prior anti-cancer therapy within 2 weeks prior to study enrollment. Prior radiation therapy within 2 weeks prior to enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed 2 days prior to study enrollment and no clinically significant toxicities are expected (eg, mucositis, esophagitis).
* Major surgery within 4 weeks prior to study enrollment.
* Current use of immunosuppressive medication at the time of study enrollment.
* Known prior or suspected hypersensitivity to investigational products.
* 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.
* Vaccination within 4 weeks of study enrollment and while on trial is prohibited except for administration of inactivated vaccines.
* Diagnosis of Myelodysplastic Syndrome.
* Patients with known brain metastases requiring steroids.
* Participation in other studies involving investigational drug(s) within 4 weeks prior to study participation and/or during study participation.
* Persisting toxicity related to prior therapy >Grade 1
* Known HIV or AIDs-related illness.
* Positive HBV or HCV test indicating acute or chronic infection.
* Active infection requiring systemic therapy.
* Clinically significant cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction within 6 months prior to study entry; unstable angina, congestive heart failure or a serious cardiac arrhythmia requiring medication.
* Current or anticipated use within 7 days prior to first dose of study drug, or anticipated use during the study of a strong P-gp inhibitor.
* Other acute or chronic medical or psychiatric conditions.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Stopped early
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
19/10/2017
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
4/01/2023
Sample size
Target
Accrual to date
Final
223
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Macquarie University - North Ryde
Recruitment hospital [2] 0 0
Northern Cancer Institute - St. Leonards
Recruitment hospital [3] 0 0
Northern Cancer Institute - Sydney
Recruitment hospital [4] 0 0
Mater Misericordiae Ltd - Brisbane
Recruitment hospital [5] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
2065 - St. Leonards
Recruitment postcode(s) [3] 0 0
2065 - Sydney
Recruitment postcode(s) [4] 0 0
4101 - Brisbane
Recruitment postcode(s) [5] 0 0
6150 - Murdoch
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arkansas
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
Minnesota
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Texas
Country [9] 0 0
Belgium
State/province [9] 0 0
Brussels
Country [10] 0 0
Belgium
State/province [10] 0 0
Bruxelles
Country [11] 0 0
Belgium
State/province [11] 0 0
Charleroi
Country [12] 0 0
Canada
State/province [12] 0 0
Alberta
Country [13] 0 0
Canada
State/province [13] 0 0
Ontario
Country [14] 0 0
Denmark
State/province [14] 0 0
Copenhagen
Country [15] 0 0
Denmark
State/province [15] 0 0
Herlev
Country [16] 0 0
Hungary
State/province [16] 0 0
Budapest
Country [17] 0 0
Hungary
State/province [17] 0 0
Miskolc
Country [18] 0 0
Hungary
State/province [18] 0 0
Pecs
Country [19] 0 0
Korea, Republic of
State/province [19] 0 0
Incheon
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Seoul
Country [21] 0 0
Russian Federation
State/province [21] 0 0
Kaluga Region
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Chelyabinsk
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Moscow
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Omsk
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Yaroslavl
Country [26] 0 0
United Kingdom
State/province [26] 0 0
Other
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Leicester
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Newcastle Upon Tyne

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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.
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests


What supporting documents are/will be available?




Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT03330405