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

NCT04187833 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE2619
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Metastatic or Unresectable Melanoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response as Defined by RECIST 1.1 Criteria

  Best overall response, defined as complete response (CR) and partial response (PR) by RECIST 1.1 criteria. Complete response (CR) is defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. Partial response (PR) is defined as a ≥30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions.

  up to 24 months after treatment through study completion, an average of 2 years

Secondary Outcomes (5)

• Progression Free Survival (PFS)

  up to 24 months after treatment through study completion, an average of 2 years

• Number of Participants With Treatment-related Adverse Events

  30 days after start of treatment

• Immune-related Overall Response (irOR) Defined by irRECIST

  up to 24 months after treatment through study completion, an average of 2 years

• Immune-related Progression Free Survival (irPFS)

  up to 24 months after treatment through study completion, an average of 2 years

• Overall Survival (OS)

  up to 24 months after treatment

Other Outcomes (4)

• Anti-tumor Response as Measured by Immune-infiltration of Tumor Infiltrating Lymphocytes

  At baseline, 12 weeks

• Patient Reported Outcomes for Adverse Events

  baseline and before each cycle (every 4 weeks) of nivolumab for a period of 12 months

• Evaluation of DNA Landscape as Described by Total Somatic Mutation Burden

  At baseline, 12 weeks

Study Arms (1)

Nivolumab + Talazoparib

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Talazoparib

Interventions

Nivolumab DRUG

480mg intravenously every 4 weeks (28 days)

Also known as: Opdivo

Nivolumab + Talazoparib

Talazoparib DRUG

1mg orally daily

Also known as: Talzenna

Nivolumab + Talazoparib

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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).

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (1)

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Neoplasm Metastasis

Interventions

Nivolumab; talazoparib

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: James Isaacs, MD
• Organization: Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

TaussigResearch@ccf.org

1-866-223-8100

Study Officials

• James Isaacs, MD

  Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2019
• First Posted: December 5, 2019
• Study Start: June 5, 2020
• Primary Completion: October 13, 2023
• Study Completion: October 13, 2023
• Last Updated: January 14, 2025
• Results First Posted: January 14, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)