Nivolumab in Combination With Talazoparib in Melanoma and Mutations in BRCA or BRCA-ness Genes

  • STATUS
    Recruiting
  • End date
    Jan 1, 2024
  • participants needed
    37
  • sponsor
    Case Comprehensive Cancer Center
Updated on 15 May 2021

Summary

The purpose of this study is to evaluate how effective the study drugs, nivolumab (also known as Opdivo) and talazoparib (also known as Talzenna) are when given as a combination treatment for unresectable or metastatic melanoma. The study team wants to know the effectiveness of these drugs together in treating cancer than if each study drug was given by itself.

Description

This is a phase II, single arm, multi-institutional, open label trial in a sample size of 37 primary or recurrent, unresectable or metastatic melanoma patients progressed on prior checkpoint inhibitor therapy with germline or somatic mutations in BRCA1/2 or BRCA-ness.

The primary objective of this study is to estimate the clinical efficacy of nivolumab plus talazoparib in patients with unresectable or metastatic melanoma with BRCA1/2 or other DNA damage repair mutations (defined as BRCA-ness)

Secondary objectives and their endpoints include progression free survival (PFS) defined as time from first dose of treatment until disease progression, treatment related adverse events, anti-tumor activity , and immune-related progression free survival (irPFS).

Details
Condition Metastatic or Unresectable Melanoma
Treatment Nivolumab, Talazoparib
Clinical Study IdentifierNCT04187833
SponsorCase Comprehensive Cancer Center
Last Modified on15 May 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Subjects must have a germline or somatic DNA damage repair mutation including any one of the following: BRCA1, BRCA2, ATM, CHEK1, CHEK2, PALB2, RAD50, RAD51, NBN, BLM, BRIP1, ATR, PARP1, MDC1, DSS1, ERCC3, MRE11, HDAC2, FANCA, MLH3, MLH1, EMSY, BAP1, LIG4, LIG3, PRKDC, XRCC6. The result may have been obtained from one of the following test providers: Myriad Genetics, Invitae, Ambry, Quest, Color Genomics, IMPACT, Foundation Medicine (tissue or ctDNA based), Guardant, or another CLIA approved tissue and/or serum based next generation sequencing-based assay
Subjects must have histologically or cytologically confirmed diagnosis of primary or recurrent metastatic melanoma
Subjects must have received prior checkpoint inhibitor therapy (defined as anti-CTLA4 or anti-PD-1 or combination anti-CTLA4/anti-PD-1), either for metastatic or unresectable disease or adjuvant therapy
ECOG Performance status 2
Subjects must have normal organ and marrow function as defined below
Hemoglobin 9.0 g/dl
Absolute neutrophil count 1,500/mcL
Platelet count 90,000/mcL
Bilirubin 1.5 x ULN (except in subjects with Gilbert Syndrome, who can have a total bilirubin < 3.0mg/dL)
AST (SGOT) 3.0 X upper limit of normal
ALT (SGPT) 3.0 X upper limit of normal
Serum Creatinine Clearance 30mL/minute. See section 7.1 for talazoparib dose adjustment for renal impairment
CrCl< 30mL/minute has not been studied in talazoparib
Measurable disease as defined by RECIST 1.1 criteria
During screening, while taking study drug, and until 5 months after taking the final dose of study drug, women of childbearing potential (WOCBP) must practice one of the following methods of birth control
Use double-barrier contraception method defined as male use of a condom and female use of a barrier method (e.g., contraceptive sponge, spermicidal jelly or cream, diaphragm [always use with spermicidal jelly/cream])
Use of hormonal contraceptives (oral, parenteral, vaginal, or transdermal) for at least 3 months before the first study drug administration
Use of an intrauterine device
Have a male partner who has had a vasectomy (at least 6 months prior to study enrollment)
Or must abstain from sexual intercourse completely
During screening, while taking study drug, and until 7 months after taking the final dose of study drug, men who are sexually active with WOCBP must practice one of the following methods of birth control
Have had a vasectomy (at least 6 months prior to study enrollment)
Use double-barrier contraception method defined as male use of a condom and female use of a barrier method (e.g., contraceptive sponge, spermicidal jelly or cream, diaphragm [always use with spermicidal jelly/cream])
Partner use of an intrauterine device
Partner use of hormonal contraceptives (oral, parenteral, vaginal, or transdermal) for at least 3 months before the first study drug administration
Or must abstain from sexual intercourse completely
Subjects must have the ability to understand and the willingness to sign a written informed consent document
Ability to swallow pills

Exclusion Criteria

Prior treatment with a PARP inhibitor
Prior anti-cancer therapy for melanoma less than 14 days prior to first dose of study drug
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
Subjects with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
Known HIV or AIDS-related illness HIV-positive subjects on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with talazoparib. In addition, these subjects are at increased risk of lethal infections when treated with marrow suppressive therapy. Appropriate studies will be undertaken in subjects receiving combination antiretroviral therapy when indicated
Prior organ transplantation including allogeneic stem-cell transplantation
Poorly controlled or uncontrolled autoimmune disease that might deteriorate when receiving an immunostimulatory agent. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition or prior therapy requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. Patients with endocrinopathies controlled on replacement drugs are eligible
Major surgery within 4 weeks prior to study enrollment
Current use of corticosteroids at the time of study enrollment, EXCEPT for the
following
a. Intranasal, inhaled, topical steroids, eye drops or local steroid injection (eg, intra-articular injection)
b. Systemic corticosteroids at physiologic doses 10 mg/day of prednisone or equivalent
c. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)
Diagnosis of Myelodysplastic Syndrome (MDS)
Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or detectable HCV RNA if anti-HCV antibody screening test positive)
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 inhibitor of breast cancer resistance protein (BCRP) (curcumin, cyclosporine, elacridar [GF120918], and eltrombopag)
Inability to swallow capsules or known intolerance to talazoparib or its excipients
Pregnant women are excluded from this study because animal studies have demonstrated that nivolumab and talazoparib may cause fetal harm when administered to pregnant women. Breastfeeding women are excluded from this study because nivolumab and talazoparib may be excreted in human breastmilk and the potential for serious adverse reactions in nursing infants
Persisting toxicity related to prior therapy > Grade 1
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