locally advanced (primary or recurrent) or metastatic solid tumors with a pathogenic or likely pathogenic germline or loss-of-function somatic BRCA1, or BRCA2, or ATM gene defect MedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864 MedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Bavencio
Product Name: Avelumab
Product Code: MSB0010718C
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Avelumab
CAS Number: 319460-85-0
Current Sponsor
BMN 673)
Pharmaceutical Form: Capsule
INN or Proposed INN: Talazoparib
CAS Number: 1373431-65-2
Current Sponsor code: PF-06944076
Other descriptive name: MDV3800
BMN 673
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.25-
Product Name: Talazoparib
Product Code: PF-06944076 (MDV3800
BMN 673
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Sponsors
Pfizer Inc., 235 East 42nd Street, New York, NY 10017
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Pathogenic or likely pathogenic germline or somatic gene defect as determined by local assessment and classification: - One or more BRCA1 or BRCA2 gene defect (Cohort 1); - ATM gene defect in the absence of concurrent BRCA 1/2 defect (Cohort 2). 2. Histological diagnosis of locally advanced (primary or recurrent) or metastatic solid tumors that are not amenable for treatment with curative intent, as follows: a. Recurrent Epithelial Ovarian Cancer; b. TNBC (defined as ER- and PgR-negative [IHC nuclear staining 28 days prior to enrollment, indicating that the patient
Exclusion criteria
Exclusion criteria: 1. Prior treatment with a PARP inhibitor. 2. Prior immunotherapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody. 3. Prior anti-cancer therapy within 2 weeks prior to study enrollment or prior radiation therapy within 2 weeks prior to study enrollment. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided it has been completed at least 2 days prior to study enrollment and no clinically significant toxicities are expected (eg, mucositis, esophagitis). 4. Major surgery within 4 weeks prior to study enrollment. 5. Current use of immunosuppressive medication at the time of study enrollment, EXCEPT for the following permitted steroids: see Section 4.2. 6. Known prior severe hypersensitivity to investigational products or any component in their formulations, including known severe hypersensitivity reactions to monoclonal antibodies ([NCI CTCAE] v4.03 Grade = 3). 7. Known history of immune-mediated colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis. 8. Active or prior autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Patients with diabetes type I, vitiligo, psoriasis, or hypoor hyperthyroid disease not requiring immunosuppressive treatment are eligible. 9. Prior organ transplantation including allogenic stem-cell transplantation. 10. Administration of live attenuated vaccines within 4 weeks of study enrollment. 11. Diagnosis of myelodysplastic syndrome (MDS). 12. Known symptomatic brain metastases requiring steroids. Patients with previously diagnosed brain metastases are eligible if they have completed their treatment and have recovered from the acute effects of radiation therapy or surgery prior to study enrollment, have discontinued corticosteroid treatment for these metastases for at least 4 weeks, and are neurologically stable. 13. Participation in other studies involving investigational drug(s) within 4 weeks prior to study entry and/or during study participation. 14. Persisting toxicity related to prior therapy (NCI CTCAE v4.03 Grade >1); however, alopecia and sensory neuropathy Grade = 2, or other Grade = 2 AEs not constituting a safety risk, based on investigator's judgment, are acceptable. 15. Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 16. Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive). 17. Active infection requiring systemic therapy. Minor infections, eg, periodontal or urinary tract infection (UTI) infection, which may be treated with short term oral antibiotics are allowed. 18. Clinically significant (ie, active) cardiovascular disease: cerebral vascular accident/stroke (<6 months prior to study enrollment), myocardial infarction (<6 months prior to study enrollment), unstable angina, congestive heart failure (= New York Heart Association Classification Class II), or a serious cardiac arrhythmia requiring medication. 19. Current or anticipated use of a P-glycoprotein (P-gp) inhibitor (amiodarone, carvedilol, clarithromycin, cobicistat, darunavir, dronedarone, erythromycin, indinavir , itraconazole, ketoconazole, lapatinib, lopinavir, propafenone, quinidine, ranolazine, ritonavir, saquinavir, telaprevir, tipranavir, valspodar, and verapamil), P-gp inducer (avasimibe, carbamazepine, phenytoin, rifampin, and St. John’s wort), or i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate ORR of avelumab in combination with talazoparib, in patients with locally advanced or metastatic solid tumors harboring BRCA1, BRCA2 or ATM defect.;Secondary Objective: - To assess the overall safety and tolerability of avelumab in combination with talazoparib. - To characterize the PK of avelumab and talazoparib when given in combination. - To evaluate the immunogenicity of avelumab when given in combination with talazoparib. - To assess other measures of the anti-tumor activity of avelumab in combination with talazoparib. - To assess the correlation of anti-tumor activity of avelumab in combination with talazoparib with PD-L1 expression in baseline tumor tissue. - To assess the correlation of anti-tumor activity and emergence of resistance with defects in a panel of key oncogenes, including BRCA 1/2 and ATM, and TMB in circulating tumor DNA (ctDNA) and tumor tissue at baseline, during treatment and at the end of treatment.;Primary end point(s): 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 (BICR), using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1 and PCWG3 (bone).;Timepoint(s) of evaluation of this end point: For patients with solid tumors, except mCRPC: Objective response (OR) is defined as a CR or PR per RECIST v1.1 from the first dose of study treatment until disease progression or death due to any cause. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response are first met. For patients with mCRPC: Objective response (OR) is defined as the proportion of patients with a best overall soft tissue response of CR or PR per RECIST v1.1 from the first dose of study treatment until disease progression or death due to any cause. Soft tissue responses will be confirmed by a follow-up radiographic assessment at least 4 weeks later with a repeated CT or MRI with no evid | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Adverse Events as characterized by type, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events [NCI CTCAE] v.4.03), timing, seriousness, and relationship to study therapy. - Laboratory abnormalities as characterized by type, severity (as graded by NCI CTCAE v.4.03) and timing. - PK parameters including: pre-dose/trough concentrations (Ctrough) for avelumab and talazoparib and post-dose concentrations (for talazoparib) and maximum concentrations (Cmax) for avelumab. - Avelumab Anti-drug antibody (ADA) levels and neutralizing antibodies (Nab) against avelumab. - Confirmed OR as assessed by the investigator, using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1 and PCWG3. - Time to event endpoints: Endpoints as assessed by BICR and as assessed by the investigator, using RECIST v1.1 and in patients with mCRPC, RECIST v1.1 and PCWG3, including time to tumor response (TTR), duration of response (DR), and progression free survival (PFS). Additional time-to-event endpoints include overall survival (OS) for all patients and time to prostate-specific antigen (PSA) progression (= 25% increase) for mCRPC patients. - PSA response = 50% decrease and CTC count conversion for patients with mCRPC. - Cancer antigen (CA)-125 response = 50% decrease for patients with ovarian cancer. - PD-L1 expression level in baseline tumor tissue - Presence of defects in a panel of key oncogenes, including BRCA1/2 and ATM, and TMB in ctDNA and tumor tissue at baseline, during treatment, and at the end of treatment.;Timepoint(s) of evaluation of this end point: multiple timepoints as per protocol | — |
Countries
Argentina, Belgium, Denmark, France, Israel, Italy, Netherlands, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trials.gov Call Centre
Pfizer Inc.
Outcome results
None listed