Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma

NCT04091750 | Active Not Recruiting Phase 2 Results DMC FDA Drug

• 1 other identifier: STUDY00000904
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 3

Brief Summary

In this phase II advanced melanoma study, all patients will receive treatment with nivolumab/ipilimumab plus cabozantinib for a 12 week induction period followed by nivolumab plus cabozantinib maintanence to complete up to 2 years of therapy unless disease progression, dose limiting toxicity, provider/patient decision or patient withdrawal of consent occurs. The primary endpoint is the one year PFS rate. Patients will have staging scans at baseline and every 12 weeks during the first 2 years on study. Safety evaluations including labs, EKG and history and physical will occur at each visit. Baseline tumor sample is required and on treatment biopsy will be optional of superficial tumor in the skin, subcutaneous tissue or lymph node that is palpable.

Conditions

Melanoma

Keywords

melanoma

Outcome Measures

Primary Outcomes (1)

• The Progression Free Survival (PFS) for Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  The PFS rate for nivolumab/ipilimumab plus cabozantinib in patients with unresectable advanced melanoma using imRECIST.

  1 year

Secondary Outcomes (3)

• The Response Rate of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  1 year

• The Overall Survival (OS) of Patients With Unresectable Advanced Melanoma Treated With Nivolumab/Ipilimumab Plus Cabozantinib.

  3 years

• The Incidence of Treatment-emergent Adverse Events of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  2 years

Other Outcomes (3)

• Associations Between Baseline Tumor Mutational Burden (TMB), Angiogenesis Pathways, and Immunophenotyping With Clinical Activity of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  3 years

• Associations Between Baseline Mutations in Genes Regulating Anti-tumor Immunity With Tumor Immunophenotype and Clinical Activity of Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  3 years

• On Treatment Biopsy for Evidence of Increased Immune Infiltration, Vascularization, and MHC Expression to Nivolumab/Ipilimumab Plus Cabozantinib in Patients With Unresectable Advanced Melanoma.

  1 year

Study Arms (1)

Single Arm

EXPERIMENTAL

Nivolumab 3mg/kg IV plus Ipilimumab 1mg/kg IV every 3 weeks x 4 cycles with Cabozantinib 40mg PO daily for 12 weeks (Induction); Followed by Maintenance therapy: Nivolumab 480mg IV every 4 weeks for up to 92 weeks; Cabozantinib 40mg PO daily for up to 92 weeks; Maintenance therapy will continue for up to 92 weeks to complete 2 years total of treatment if tolerating therapy well and disease is controlled.

Drug: Nivolumab; Drug: Ipilimumab; Drug: Cabozantinib

Interventions

Nivolumab DRUG

Induction: 3mg/kg IV every 3 weeks x 4 cycles Maintenance: 480mg IV every 4 weeks for up to 92 weeks

Also known as: Opdivo

Single Arm

Ipilimumab DRUG

Induction: 1mg/kg IV every 3 weeks x 4 cycles

Also known as: Yervoy

Single Arm

Cabozantinib DRUG

Induction and Maintenance: 40mg PO daily

Also known as: Cabometyx

Single Arm

Eligibility Criteria

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

You may qualify if:

• All patients must have unresectable stage IIIb-IIId or IV melanoma by AJCC 8th edition. Note: Patients with uveal melanoma are excluded from this study.
• Age \> 18 and ECOG Performance Status of 0 or 1.
• Measurable disease by RECIST 1.1
• Baseline tumor specimen available.
• Recovery to baseline or ≤ Grade 1 CTCAE v4 from toxicities related to any prior treatments, unless AE(s) are clinically nonsignificant and/or stable on supportive therapy.
• Adequate organ and marrow function.
• Capable of understanding and complying with the protocol requirements and must have signed the informed consent document.
• Sexually active fertile subjects and their partners must agree to use medically accepted methods of contraception (eg, barrier methods, including male condom, female condom, or diaphragm with spermicidal gel) during the course of the study and for 4 months after the last dose of study treatment.
• Female subjects of childbearing potential must not be pregnant at screening.

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1 therapy, anti-CTLA-4 therapy or cabozantinib. Prior adjuvant anti-PD-1 and/or anti-CTLA-4 therapy is allowed if relapse is greater than 6 months from last dose.
• Receipt of any type of small molecule kinase inhibitor (including investigational kinase inhibitor) within 2 weeks before first dose of study treatment.
• Receipt of any type of cytotoxic, biologic or other systemic anticancer therapy (including investigational) within 4 weeks before first dose of study treatment.
• Radiation therapy for bone metastasis or brain metastasis within 2 weeks, any other radiation therapy within 4 weeks before first dose of study treatment. Systemic treatment with radionuclides within 6 weeks before the first dose of study treatment.
• Known brain metastases that are \>10mm or cranial epidural disease unless adequately treated with radiosurgery and/or surgery (including radiosurgery). Eligible subjects must be neurologically asymptomatic and without corticosteroid requirement. Dexamethasone \< 2mg daily (or equivalent) will be allowed if discontinuation of corticosteroids is not feasible due to post-radiation effects and patient is asymptomatic. Patients with active, asymptomatic brain metastases that are \<10mm and no corticosteroid requirement will be allowed without radiosurgery or surgery.
• History of active autoimmune disorder requiring immunosuppressive agents. Patients with autoimmune disorders considered low risk, such as vitiligo and thyroiditis, will be allowed.
• Concomitant anticoagulation with coumarin agents (e.g., warfarin), direct thrombin inhibitors (e.g. dabigatran), betrixaban, or platelet inhibitors (eg, clopidogrel).
• Allowed anticoagulants are the following:
• Prophylactic use of Low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH) are permitted.
• Anticoagulation with therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban is allowed in subjects without known brain metastases who are on a stable dose of LMWH anticoagulant for at least 6 weeks 1week before first dose of study treatment, and who have had no clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.
• The subject has prothrombin time (PT)/INR or partial thromboplastin time (PTT) test ≥ 1.3 x the laboratory ULN within 7 days before the first dose of study treatment.
• The subject has uncontrolled, significant intercurrent or recent illness.
• Major surgery (eg, GI surgery, removal or biopsy of brain metastasis) within 8 weeks before first dose of study treatment.
• Corrected QT interval calculated by the Fridericia formula (QTcF) \> 500 ms per electrocardiogram (ECG) within 28 days before first dose of study treatment.
• Pregnant or lactating females.

Sponsors & Collaborators

• Georgetown University: lead
• MedStar Franklin Square Medical Center: collaborator
• Hackensack Meridian Health: collaborator
• Exelixis: collaborator

Study Sites (3)

Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

Location

Medstar Franklin Square Medical Center, Harry and Jeanette Weinberg Cancer Institute

Baltimore, Maryland, 21237, United States

Location

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; Ipilimumab; cabozantinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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: Geoffrey T. Gibney, MD
• Organization: Georgetown University

Geoffrey.T.Gibney@gunet.georgetown.edu

202-444-2223

Study Officials

• Geoffrey T Gibney, MD

  MedStar Georgetown University Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

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: September 13, 2019
• First Posted: September 17, 2019
• Study Start: March 2, 2020
• Primary Completion: August 8, 2023
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 3, 2026
• Results First Posted: November 27, 2024

Record last verified: 2026-02

Locations

US (3)