Duvelisib in Combination with Nivolumab for Treatment of Unresectable Stage IIIB-IV Melanoma

Active:	Yes
Cancer Type:	Melanoma	NCT ID:	NCT04688658
Trial Phases:	Phase I Phase II	Protocol IDs:	HCC 20-155 (primary) NCI-2021-13070
Eligibility:	18 Years and older, Male and Female	Study Type:	Treatment
Study Sponsor:	University of Pittsburgh Cancer Institute (UPCI)
NCI Full Details:	http://clinicaltrials.gov/show/NCT04688658

Summary

This phase I/II trial studies the side effects and best dose of duvelisib in combination with nivolumab and to see how well they work in treating patients with stage IIIB-IV melanoma that cannot be removed by surgery (unresectable). Duvelisib is in a class of medications called kinase inhibitors. It works by blocking the signals that cause cancer cells to multiply. This helps to stop the spread of cancer cells. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving duvelisib and nivolumab may help re-sensitize melanoma tumors to respond to anti-PD1 therapy.

Objectives

PRIMARY OBJECTIVES:
I. To determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of duvelisib when combined with anti-PD1 therapy nivolumab by immunologic profiling and toxicity data. (Phase I)
II. To assess the anti-tumor activity of the combination of duvelisib and nivolumab therapy, comparing disease change documented in computed tomography (CT) measurements 12 weeks after initiation of therapy to baseline scans, and every 12 weeks thereafter. (Phase II)

SECONDARY OBJECTIVE:
I. To assess early (within 4 weeks) and late toxicities (after 4 weeks) of combination duvelisib and nivolumab. (Phase I)
II. To assess the anti-tumor activity of the combination of duvelisib and nivolumab therapy, comparing disease change documented in CT measurements 12 weeks after initiation of therapy to baseline scans, and every 12 weeks thereafter. (Phase I)
III. To assess the potential antitumor response of the combination of duvelisib and anti-PD1 therapy. (Phase II)
IV. To assess the duration of response with this combination. (Phase II)
V. To assess progression-free survival and overall survival. (Phase II)
VI. To assess the safety of the combination of duvelisib and anti-PD1 therapy. (Phase II)
VII. To evaluate differences in response between certain pre-specified subsets of melanoma patients, including those who progressed on anti-PD1 therapy within 3 months (early progressors) and those who progressed after 3 months (late progressors), as well as by BRAF mutation status. (Phase II)

EXPLORATORY OBJECTIVES:
I. To evaluate how immune cell populations change by duvelisib dose, to help inform recommended phase II dosing.
II. To evaluate the effects of duvelisib on the tumor microenvironment (TME).
III. To explore mechanism of anti-PD1 resistance and the role of duvelisib in overcoming this resistance.

OUTLINE: This is a phase I, dose-escalation study of duvelisib followed by a phase II study.

Patients receive duvelisib orally (PO) once daily (QD) or twice daily (BID) on days 1-28. Patients also receive nivolumab intravenously (IV) over 30 minutes on days 1 and 14 of cycles 1-4 and day 1 of subsequent cycles. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then every 3 months for up to 5 years.

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