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Trial details imported from ClinicalTrials.gov

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




Registration number
NCT03330405
Ethics application status
Date submitted
16/10/2017
Date registered
6/11/2017
Date last updated
18/06/2020

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
Dose Limiting Toxicity (DLT) - Phase 1b: DLT during the DLT evaluation period (Cycle 1)
Timepoint [1] 0 0
Cycle 1 Days 1-28 (28 days from date of first dose of study treatment)
Primary outcome [2] 0 0
Overall Response (OR) - Phase 2: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC
Timepoint [2] 0 0
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
Secondary outcome [1] 0 0
Serum concentrations of avelumab - Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
Timepoint [1] 0 0
Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1
Secondary outcome [2] 0 0
Anti drug antibody (ADA) levels of avelumab - Immunogenicity assessment of avelumab
Timepoint [2] 0 0
Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1
Secondary outcome [3] 0 0
OR - Phase 1b: Confirmed OR, as assessed by the Investigator using RECIST v1.1 in patients with locally advanced or metastatic solid tumors and RECIST v1.1 and PCWG3 in patients with metastatic CRPC.
Timepoint [3] 0 0
From the start of treatment until disease progression/recurrence up to approximately 24 months
Secondary outcome [4] 0 0
PSA Tumor Marker - PSA response greater than or equal to 50% for patients with metastatic CRPC.
Timepoint [4] 0 0
Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment ( up to approximately 24 months)
Secondary outcome [5] 0 0
CA-125 Tumor Marker - CA-125 response for patients with ovarian cancer.
Timepoint [5] 0 0
Baseline, Day1 of each cycle (each cycle is 28 days), and End of Treatment (up to approximately 24 months)
Secondary outcome [6] 0 0
Biomarker PD-L1 - PD-L1 expression level in baseline tumor tissue.
Timepoint [6] 0 0
Baseline
Secondary outcome [7] 0 0
Genomic - Genomic scarring and the presence of defects in select genes, considered critical to effective DDR, in baseline tumor tissue.
Timepoint [7] 0 0
Baseline
Secondary outcome [8] 0 0
Serum concentrations of avelumab - Pharmacokinetic parameters: maximum concentrations (Cmax)
Timepoint [8] 0 0
Day 1 Cycles 1-4, 6,9,12,18, 24 and Day 15 Cycle 1
Secondary outcome [9] 0 0
Plasma concentrations of talazoparib - Pharmacokinetic parameters: pre-dose/trough concentrations (Ctrough)
Timepoint [9] 0 0
Day 1 Cycles 1-4 and Day 15 Cycle 1
Secondary outcome [10] 0 0
Plasma concentration of talazoparib - Pharmacokinetic parameters: post-dose concentrations
Timepoint [10] 0 0
Day 1 Cycles 1-4 and Day 15 Cycle 1
Secondary outcome [11] 0 0
Neutralizing antibodies (Nab) levels against avelumab. - Immunogenicity assessment of avelumab
Timepoint [11] 0 0
Day 1 Cycles 1-4, 6, 9, 12, 18, 24 and Day 15 Cycle 1
Secondary outcome [12] 0 0
Time to Tumor Response (TTR) - Time to Tumor Response (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.
Timepoint [12] 0 0
Baseline up to approximately 24 months
Secondary outcome [13] 0 0
Duration of response (DR) - Duration of Response (DR) is defined for patients with confirmed objective response (complete response [CR] or partial response [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.
Timepoint [13] 0 0
Baseline up to approximately 24 months
Secondary outcome [14] 0 0
Progression-Free Survival (PFS) - Progression Free Survival (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.
Timepoint [14] 0 0
Baseline up to approximately 24 months
Secondary outcome [15] 0 0
Prostate-Specific Antigen (PSA) response - PSA response is defined as the proportion of patients with confirmed PSA decline greater than or equal to 50% compared to baseline.
Timepoint [15] 0 0
Baseline up to approximately 24 months
Secondary outcome [16] 0 0
Overall Survival (OS) - OS is defined as the time from the first dose of study treatment to the date of death.
Timepoint [16] 0 0
Baseline up to approximately 24 months
Secondary outcome [17] 0 0
Biomarker Tumor Mutational Burden - Tumor mutational burden in baseline tumor tissue
Timepoint [17] 0 0
Baseline

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
Gender
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 2
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
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 - Sydney
Recruitment hospital [3] 0 0
Mater Misericordiae Ltd - Brisbane
Recruitment hospital [4] 0 0
Fiona Stanley Hospital - Murdoch
Recruitment postcode(s) [1] 0 0
2109 - North Ryde
Recruitment postcode(s) [2] 0 0
2065 - Sydney
Recruitment postcode(s) [3] 0 0
4101 - Brisbane
Recruitment postcode(s) [4] 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
Michigan
Country [6] 0 0
United States of America
State/province [6] 0 0
Minnesota
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Texas
Country [10] 0 0
Belgium
State/province [10] 0 0
Brussels
Country [11] 0 0
Belgium
State/province [11] 0 0
Bruxelles
Country [12] 0 0
Belgium
State/province [12] 0 0
Charleroi
Country [13] 0 0
Canada
State/province [13] 0 0
Alberta
Country [14] 0 0
Canada
State/province [14] 0 0
Ontario
Country [15] 0 0
Denmark
State/province [15] 0 0
Copenhagen
Country [16] 0 0
Denmark
State/province [16] 0 0
Herlev
Country [17] 0 0
Hungary
State/province [17] 0 0
Budapest
Country [18] 0 0
Hungary
State/province [18] 0 0
Miskolc
Country [19] 0 0
Hungary
State/province [19] 0 0
Pecs
Country [20] 0 0
Korea, Republic of
State/province [20] 0 0
Incheon
Country [21] 0 0
Korea, Republic of
State/province [21] 0 0
Seoul
Country [22] 0 0
Russian Federation
State/province [22] 0 0
Kaluga Region
Country [23] 0 0
Russian Federation
State/province [23] 0 0
Chelyabinsk
Country [24] 0 0
Russian Federation
State/province [24] 0 0
Moscow
Country [25] 0 0
Russian Federation
State/province [25] 0 0
Omsk
Country [26] 0 0
Russian Federation
State/province [26] 0 0
Yaroslavl
Country [27] 0 0
United Kingdom
State/province [27] 0 0
Other
Country [28] 0 0
United Kingdom
State/province [28] 0 0
Leicester
Country [29] 0 0
United Kingdom
State/province [29] 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
Avelumab in combination with talazoparib will be investigated in patients with locally
advanced (primary or recurrent) or metastatic solid tumors, including non-small cell lung
cancer (NSCLC), triple negative breast cancer (TNBC), hormone receptor positive (HR+) breast
cancer, recurrent platinum sensitive ovarian cancer, urothelial cancer (UC), and castration
resistant prostate cancer (CRPC).
Trial website
https://clinicaltrials.gov/show/NCT03330405
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

Summary results
Other publications