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
- Conditions
- 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 defectMedDRA version: 20.0 Level: LLT Classification code 10065147 Term: Malignant solid tumor System Organ Class: 100000004864MedDRA version: 20.0 Level: LLT Classification code 10065252 Term: Solid tumor System Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000345-39-GB
- Lead Sponsor
- Pfizer Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Not specified
- Target Recruitment
- 541
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 <5%] and HER2-negative [IHC 0, 1+, or 2+ and/or ISH non-amplified with ratio less than 2.0]) or hormone-receptor-positive (HR+), HER2-negative breast cancer;
c. Metastatic castration-resistant prostate cancer (mCRPC) without small cell features;
d. Metastatic ductal adenocarcinoma of the pancreas;
e. Any other advanced solid tumor.
3. Availability of a fresh or recent tumor tissue sample from a diagnostic biopsy/surgery or a metastatic tumor biopsy; the sample must have been obtained within 24 months prior to study enrollment. When only bone disease is present, an archival tumor tissue sample obtained within 5 years prior to study enrollment may be accepted for non-prostate cancer patients and a fresh bone biopsy may be accepted for prostate cancer patients only).
4. Have progressive disease at study enrollment as defined by RECIST v1.1 (except for mCRPC, who must meet criterion 2c above).
5. Must have measurable disease by RECIST v1.1 with at least 1 measurable lesion that has not been previously irradiated (patients with mCRPC may have only non-measurable disease).
6. Age =18 years (except in Japan, where patients must be = 20 years old).
7. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
8. Adequate bone marrow function (without hematopoietic growth factor or transfusion support within 14 days prior to study enrollment), including:
a. Absolute Neutrophil Count (ANC) = 1,500/mm3 or = 1.5 x 109/L.
b. Platelets = 100,000/mm3 or =100 x 109/L.
c. Hemoglobin = 9 g/dL (= 5.6 mmol/L).
9. Adequate renal function defined by an estimated creatinine clearance = 30 mL/min according to the Cockcroft-Gault formula as:
- CLCR={[(140–age) × weight)]/(72 x SCR)} × 0.85 (if female), where CLCR (creatinine clearance) is measured in mL/min, age is expressed in years, weight inkilograms (kg), and SCR (serum creatinine) in mg/dL;
- Or as measured by 24h urine assessment.
10. Adequate liver function, including:
a. Total serum bilirubin = 1.5 × the upper limit of normal range (ULN);
b. Aspartate and Alanine aminotransferase (AST and ALT) = 2.5 x ULN.
11. Female patients of childbearing potential must have negative serum pregnancy or urine pregnancy test at screening. Female patients of nonchildbearing potential must meet at least 1 of the following criteria:
- Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause and have a serum follicle-stimulating hormone (FSH) level con
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, c
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method