Safety and Efficacy in Participants With Metastatic BRAF-mutant Melanoma Treated With Encorafenib With and Without Binimetinib in Combination With Nivolumab and Low-dose Ipilimuma
(QUAD01 Trial)

Recruiting in Palo Alto (17 mi)

Overseen byJason J Luke, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Waitlist Available

Sponsor: Jason J. Luke, MD

No Placebo Group

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?Patients with unresectable or metastatic BRAF-mutant melanoma high-risk patients will be given 450 mg orally (PO) daily (QD) plus binimetinib 45 mg PO twice daily (BID) together with nivolumab administered intravenously (IV) at 3mg/kg and ipilimumab administered IV at 1 mg/kg every 3 weeks for 4 doses, followed by nivolumab administered IV at 480mg every 4 weeks until progression or discontinuation due to toxicity. Concurrently, a triple therapy arm will be explored with encorafenib 300 mg PO QD together with ipilimumab administered IV at 1mg/kg and nivolumab 3mg/kg IV every 3 weeks for 4 doses, followed by nivolumab administered at 480mg every 4 weeks until progression or discontinuation due to toxicity. Tolerability of the two arms will be compared, and a recommended phase 2 dose (RP2D) will be determined. After determination of treatment schedule, expansion cohorts will further explore the preliminary efficacy and further describe the toxicity profile of the triplet or quadruplet regimen in high-risk cohorts including symptomatic brain metastases or liver metastases with elevated lactate dehydrogenase (LDH) or bulky systemic disease burden.

Eligibility Criteria

Inclusion Criteria

Symptomatic intracranial metastases may be on steroids at a total daily dose of no higher than 4 mg of dexamethasone or equivalent that is stable or tapering for 10 days prior to first treatment, have no immediate need for SRT or surgery (within 3 week prior to first treatment), have had no experience of seizure within 10 days prior to first treatment.

Signed Written Informed Consent: Participants 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.

Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration.

+28 more

Exclusion Criteria

History or presence of clinically significant cardiac arrhythmias (including resting bradycardia, uncontrolled atrial fibrillation or uncontrolled paroxysmal supraventricular tachycardia)

Baseline QTcF interval ≥ 480 ms.

Second malignancy that requires active treatment or would interfere with treatment efficacy evaluation. Participants with a second malignancy treated with curative intent are eligible.

+17 more