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 or metastatic solid tumorsmaligne tumor10027655
- Registration Number
- NL-OMON48840
- Lead Sponsor
- Pfizer
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 22
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
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).
Note: in the event that a patient has concomitant defects in more than 1 of the three genes (BRCA1 or BRCA2 or ATM), they will be enrolled in Cohort 1.
The presence of gene defects must have been determined by local assessment and classification using a test of either germline or tumor DNA which was performed in a CAP/CLIA certified (or comparable local or regional certification) laboratory.
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:
* Patients must have received at least 1 but no more than 5 total prior cytotoxic chemotherapy regimens, including at least 1 course of platinum based therapy;
* Patients must not have progressed during or within 1 month after the last dose of the most recent platinum based chemotherapy;
* Platinum sensitivity requirements:
* If previously treated with *2 prior cytotoxic chemotherapy regimens, patients must have had disease progression within 6 months after the last dose of platinum based chemotherapy, also termed *platinum resistant recurrent disease*;
* If previously treated with >2 prior cytotoxic chemotherapy regimens, platinum sensitive recurrent disease is allowed.
* Any treatment regimen that began with cytotoxic chemotherapy and continued with another regimen for maintenance therapy following best response to initial cytotoxic regimen will count as one line of prior therapy.
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:
* Have been previously treated with no more than 3 prior chemotherapy regimens for locally advanced or metastatic breast cancer;
* There is no limit on the number of prior endocrine therapies or targeted anti cancer therapies such as mammalian target of rapamycin (mTOR) or cyclin dependent kinase (CDK)4/6 inhibitors, or vascular endothelial growth factor inhibitors (VEGF);
* Previous neo adjuvant/adjuvant treatment counts as 1 line of prior chemotherapy if disease progression occurred while on treatment or within 6 months after the last treatment dose;
* Patients must have received treatment with a taxane or anthracycline containing chemotherapy regimen in the neo adjuvant, adjuvant, or advanced setting, unless deemed unsuitable for these treatments;
* Patients that have previously been treated with platinum based chemotherapy in the neo adjuvant/adjuvant setting must not have had disease progression while on treatment or within 6 months after the last dose of platinum based chemotherapy;
* Patients that have previously been treated with platinum based chemotherapy in the advanced/metastatic setting must not have had disease progression within 6 months of initiation of a platinum-containing regimen;
* Patients with HR+ breast cancer must have received at least 1 prior endocrine therapy (adjuvant or metastatic), unless de
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 strong P-gp inhibitors within 7 days prior to enrollment,or anticipated use during the study. For a list of strong P-gp inhibitors, refer to Section 5.7.10.;20. Inability to swallow capsules, known intolerance to talazoparib or its excipients, known malabsorption syndrome, or other condition that may impair absorption of talazoparib.;21. Bisphosphonate or denosumab dosage that was not stabl
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>* Confirmed OR in patients with locally advanced or metastatic solid tumors<br /><br>with BRCA 1/2 or ATM defect, as assessed by Blinded Independent Central Review<br /><br>(BICR), using RECIST v1.1 and, in patients with mCRPC, RECIST v1.1 and PCWG3<br /><br>(bone).</p><br>
- Secondary Outcome Measures
Name Time Method