Phase I/IIa Dose Finding Study of Triplet Regimen of Relatlimab Ipilimumab and NIvolumab in First Line Therapy of Metastatic Melanoma (TRINITY)

NCT06683755 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2024-1032NCI-2024-09421
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

To determine the recommended Phase IIa dose (RP2D) of the triplet combination. To determine the safety and efficacy of the combination at the RP2D.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (1)

• Safety and Adverse Events (AEs)

  Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 5.0

  Through study completion; an average of 1 year

Study Arms (1)

Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab

EXPERIMENTAL

Participants particiapting on study will be randomized

Drug: Nivolumab; Drug: Relatlimab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

Given by IV

Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab

Relatlimab DRUG

Given by IV

Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab

Ipilimumab DRUG

Given by IV

Phase I + IIa: Nivolumab + Relatlimab + Ipilimumab

Eligibility Criteria

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

You may qualify if:

• Age ≥ 18 years old.
• ECOG performance status 0-1
• Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol-related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study.
• Histologically confirmed unresectable stage III or stage IV malignant melanoma (Stage IV).
• At least one measurable target lesion according to RECIST 1.1. (Appendix 1), which previously was not treated.
• Growth or change in a lesion previously irradiated will not be considered measurable. Regrowth in cavity of previously excised lesion will not be considered measurable
• Tumor tissue from an unresectable or metastatic site of disease must be available for biomarker analyses. The biopsy should be a core biopsy, a punch biopsy, an excisional biopsy, or a surgical specimen. Fine needle aspiration is unacceptable for submission
• For Phase I participants: Pretreatment tissue must be available through either an archival sample obtained within at most 6 months and submitted as an FFPE tissue block or 30 unstained tumor tissue slides or a fresh pretreatment biopsy. Subsequent tumor biopsies will be optional.
• For Phase IIa participants: Either an archival sample submitted as an FFPE tissue block or unstained tumor tissue slides or a fresh pretreatment biopsy from safely biopsiable lesion. Note that if the patient has archival tissue available from a biopsy within 90 days of C1D1 and there has been no systemic treatment since that time then that tissue can be used in place of a fresh pre-treatment biopsy. Patients must also agree to undergo post treatment, cycle 2, tumor biopsies for research purposes. Subsequent biopsies will be optional.
• No prior systemic lines of treatment for metastatic melanoma. Prior adjuvant or neo-adjuvant therapy will be permitted as long as it did not contain ipilimumab and the last dose has been \>6 months.
• Prior radiation is allowed with a two week wash out period prior to initiation of treatment.
• Adequate organ function as described below.
• Table 2. Evaluation of Organ Function Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1.5 X 109/L Platelets ≥ 100 X 109/L (≥ 60 for HCC) Hemoglobin ≥ 8.0 g/dL Renal Creatinine OR ≤1.5 × ULN OR Measured or calculatedb creatinine clearance ≥40 mL/min for participant with creatinine levels \>1.5 × institutional (GFR can also be used in place of creatinine or ULN CRCl) Hepatic ≤1.5 ×ULN OR direct bilirubin ≤ULN Total bilirubin for participants with total bilirubin levels AST (SGOT) and ALT (SGPT) ≤3.0 × ULN (≤5 × ULN for participants with liver metastases) Coagulation International normalized ratio (INR) OR ≤1.5 × ULN unless participant is receiving prothrombin time (PTT) anticoagulant therapy as long as PT or Activated partial thromboplastin time aPTT wi withing therapeutic range of intended use of anticoagulants (aPTT) ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal.
• a Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks.

You may not qualify if:

• Patients with ocular melanoma.
• Patients with symptomatic CNS metastases and/or requiring corticosteroid treatment.
• History of known leptomeningeal involvement (lumbar puncture not required).
• Patients who experienced Grade 3/4 immune-related adverse events with checkpoint inhibitor therapy, except those that are unlikely to re-occur with standard countermeasures (e.g. hypothyroidism) 5. Subjects with an active, known or suspected autoimmune disease. Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
• \. Subjects with major medical, neurologic or psychiatric condition who are judged as unable to fully comply with study therapy or assessments should not be enrolled.
• \. Subject has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. Note: The time requirement does not apply to participants who underwent successful treatment of superficial bladder cancer, in situ cervical cancer, or other in-situ cancers. Subjects with a completely treated prior malignancy and no evidence of disease for ≥ 2 years are eligible.
• \. History of or is positive for hepatitis B (hepatitis B surface antigen \[HBsAg\] reactive) or hepatitis C (hepatitis C virus \[HCV\] RNA \[qualitative\] is detected).
• a. NOTE: Without known history, testing needs to be performed to determine eligibility. Hepatitis C antibody (Ab) testing is allowed for screening purposes in countries where HCV RNA is not part of standard of care.
• \. History of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
• \. The use of corticosteroids is not allowed for 14 days prior to initiation of therapy (based upon 5 times the expected half-life of dexamethasone) except patients who are taking steroids for physiological replacement or in the case of Inhaled or topical steroids or other immunosuppressive medications. If alternative corticosteroid therapy has been used, consultation with the PI is required to determine the washout period prior to initiating study treatment.
• \. Major surgical procedure, open biopsy (excluding skin cancer resection), or significant traumatic injury within 14 days of initiating study drug (unless the wound has healed) or anticipation of the need for major surgery during the study.
• \. Non-healing wound, ulcer, or bone fracture. 13. Women who are breast-feeding or pregnant. 14. Uncontrolled intercurrent illness (i.e., active infection ≥ grade 2) or concurrent condition that, in the opinion of the Investigator, would interfere with the study endpoints or the subject's ability to participate.
• \. History of clinically significant cardiac disease or congestive heart failure \> New York Heart Association (NYHA) class 2. Subjects must not have unstable angina (anginal symptoms at rest) or new-onset angina within the last 3 months or myocardial infarction within the past 6 months or a history of myocarditis. Also, • prior myocarditis of any etiology. • Left ventricular ejection fraction (LVEF) assessment with documented LVEF \< 50% by either transthoracic echocardiogram (TTE) or multigated acquisition scan (TTE preferred test) within 6 months prior to the start of study treatment.
• \. Troponin T (TnT) or I (TnI) \> 2 × institutional ULN. Participants with TnT or TnI levels between \> 1 to 2 × ULN will be permitted if repeat levels within 24 hours are ≤ 1 ULN. If TnT or TnI levels are between \>1 to 2 × ULN within 24 hours, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. When repeat levels within 24 hours are not available, a repeat test should be conducted as soon as possible. If TnT or TnI repeat levels beyond 24 hours are \< 2 × ULN, the participant may undergo a cardiac consultation and be considered for treatment, following cardiologist recommendation. Notification of the decision to enroll the participant following cardiologist recommendation has to be made to the principal investigator.
• \. Investigational drug use within 14 days (or 5 half-lives, whichever is shorter) of the first dose of the triplet therapy.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

The University of Texas M. D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Melanoma

Interventions

Nivolumab; relatlimab; Ipilimumab

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

Study Officials

• Hussein Tawbi, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hussein Tawbi, MD,PHD

CONTACT

(713) 792-4185; htawbi@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 8, 2024
• First Posted: November 12, 2024
• Study Start: May 1, 2025
• Primary Completion (Estimated): August 16, 2030
• Study Completion (Estimated): August 16, 2032
• Last Updated: November 12, 2024

Record last verified: 2024-11

Locations

US (1)