Clinical Trials /

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

NCT04187833

Description:

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.

Related Conditions:
  • Melanoma
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Nivolumab in Combination With Talazoparib in Melanoma and Mutations in BRCA or BRCA-ness Genes
  • Official Title: Phase II Trial of Nivolumab in Combination With Talazoparib in Patients With Unresectable or Metastatic Melanoma and Mutations in BRCA or BRCA-ness Genes

Clinical Trial IDs

  • ORG STUDY ID: CASE2619
  • NCT ID: NCT04187833

Conditions

  • Metastatic or Unresectable Melanoma

Interventions

DrugSynonymsArms
NivolumabOpdivoNivolumab + Talazoparib
TalazoparibTalzennaNivolumab + Talazoparib

Purpose

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.

Detailed 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).
    

Trial Arms

NameTypeDescriptionInterventions
Nivolumab + TalazoparibExperimentalNivolumab 480mg intravenously every 4 weeks (28 days) + Talazoparib 1mg orally daily
  • Nivolumab
  • Talazoparib

Eligibility Criteria

        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 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:19 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Best overall response as defined by by RECIST 1.1 criteria
Time Frame:up to 24 months after treatment
Safety Issue:
Description:Best overall response, defined as complete response (CR) and partial response (PR) by RECIST 1.1 criteria

Secondary Outcome Measures

Measure:Progression Free Survival (PFS)
Time Frame:up to 24 months after treatment
Safety Issue:
Description:PFS, defined as the time from the first dose of study treatment to the date of disease progression by RECIST 1.1 or death due to any cause, whichever occurs first.
Measure:Number of participants with treatment-related adverse events
Time Frame:30 days after start of treatment
Safety Issue:
Description:Number of participants with treatment-related adverse events, as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Measure:Immune-related overall response (irOR) defined by irRECIST
Time Frame:up to 24 months after treatment
Safety Issue:
Description:Immune-related overall response (irOR), defined as immune-related complete response (irCR) and immune-related partial response (irPR) by irRECIST
Measure:Immune-related Progression Free Survival (irPFS)
Time Frame:up to 24 months after treatment
Safety Issue:
Description:irPFS, defined as the time from the first dose of study treatment to the date of disease progression by irRECIST

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Pauline Funchain

Last Updated

December 4, 2019