A Study of Dapansutrile Plus Pembrolizumab in Patients With PD-1 Refractory Advanced Melanoma

NCT04971499 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: Pro00108864
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

This phase 1/2 trial will be conducted in two parts. Part 1 (Dose Selection) is designed to find the dose of dapansutrile with acceptable tolerability in combination with pembrolizumab. Part 1 will consist of up to 2 dose selection cohorts to evaluate the safety and tolerability of dapansutrile + pembrolizumab in patients with PD-1 resistant melanoma to find the recommended part 2 dose (RP2D). Part 1 will include a lead-in phase of dapansutrile monotherapy at 500 mg PO BID. At day 15, combination therapy with pembrolizumab will be initiated. Dose escalation is planned to a maximum of 1000 mg BID of dapansutrile + pembrolizumab. Part 2 (Dose Expansion) is designed to assess preliminary efficacy of dapansutrile + pembrolizumab in PD-1 resistant melanoma. Once all patients in Part 1 have completed 4 weeks of dapansutrile therapy, the expansion phase will start enrolling. Part 2 will also include a 14-day lead-in period of dapansutrile monotherapy at the RP2D.

Conditions

Melanoma

Outcome Measures

Primary Outcomes (2)

• Number of AEs (including SAEs and DLTs) as measured by patient interview and medical record review

  90 days after last dose

• Objective response rate as measured by the percentage of patients who achieve a partial or complete response per RECIST v1.1 and iRECIST while receiving study therapy.

  Up to 2 years

Secondary Outcomes (4)

• Progression free survival as measured by the number of patients that have not experienced radiographic disease progression

  after 6 months

• Progression free survival as measured by the number of patients that have not experienced radiographic disease progression

  after 12 months

• Overall survival as measured by the number of patients who die due to any cause

  after 6 months

• Overall survival as measured by the number of patients who die due to any cause

  after 12 months

Study Arms (2)

Dose Selection

EXPERIMENTAL

Dapansutrile starting at 500 mg PO BID plus Pembrolizumab 200 mg IV every three weeks. Dose escalation is planned to a maximum of 1000 mg BID of dapansutrile + pembrolizumab.

Drug: Dapansutrile; Drug: Pembrolizumab

Dose Expansion

EXPERIMENTAL

Dapansutrile at the RP2D plus Pembrolizumab 200 mg IV every three weeks

Drug: Dapansutrile; Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Single-use vial containing 100 mg/4 mL of pembrolizumab

Dose Expansion; Dose Selection

Dapansutrile DRUG

500 mg tablet

Dose Expansion; Dose Selection

Eligibility Criteria

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

You may qualify if:

• Has histologically or cytologically confirmed melanoma.
• Has unresectable Stage III or Stage IV melanoma, per AJCC 8th Edition Staging Criteria, not amenable to local therapy.
• Male or female participants who are at least 18 years of age on the day of signing informed consent
• Male participants must agree to use a reliable method of contraception (refer to Section 6.4.1) during the treatment period and for at least 120 days after the last dose of study drug and must refrain from donating sperm during this period.
• Female participants must not be pregnant or breast feeding and meet at least one of the following conditions:
• Not a woman of childbearing potential (WOCBP)
• A WOCBP must agree to use a reliable method of contraception (refer to Section 6.4.1) during the treatment period and for at least 120 days after the last dose of study treatment.
• Participants must have received an anti-PD-1/PD-L1 mAb as part of their most recent line of therapy prior to enrollment in the study.
• Participants must have progressed on or after treatment with an anti-PD-1/PD-L1 mAb administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies in their most recent line of therapy. PD 1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 8 weeks of an anti-PD-1/PD-L1 mAb
• Has demonstrated progression after anti-PD-1/PD-L1 mAb therapy as defined by RECIST v.1.1. The initial evidence of progressive disease (PD) is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression (as defined in 7.c)
• Progressive disease has been documented within 6 months from the last dose of anti-PD-1/L1 mAb.
• i. Progressive disease must be determined according to iRECIST ii. This determination is made by the investigator. Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression.
• The participant provides written informed consent for the trial
• Measurable disease based on RECIST v.1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions

You may not qualify if:

• Ocular or mucosal melanoma
• A WOCBP who is pregnant or breastfeeding or has a positive pregnancy test within 72 hours prior to receiving study treatment
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks prior to starting study treatment
• Has received prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
• Has received cytotoxic chemotherapy for melanoma at any point prior to study enrollment
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention
• Has received an additional line of therapy after the PD-1/PD-L1 therapy prior to starting on this study.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 14 days prior to the first dose of study drug
• History of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years
• a. Exception: time requirement does not apply to patients who underwent successful definitive resection of basal cell carcinoma of the skin, squamous cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in situ cancers
• Known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate, provided the patient is clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention
• Severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
• History of (non-infectious) pneumonitis/ interstitial lung disease that required steroids or has current pneumonitis/ interstitial lung disease
• Active infection requiring systemic therapy

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: collaborator
• Olatec Therapeutics LLC: collaborator
• April Salama, M.D.: lead

Study Sites (1)

Duke Cancer Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Conditions

Melanoma

Interventions

dapansutrile; pembrolizumab

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

Study Officials

• April Salama

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: July 12, 2021
• First Posted: July 21, 2021
• Study Start: September 6, 2022
• Primary Completion (Estimated): April 30, 2027
• Study Completion (Estimated): April 30, 2027
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR

Locations

US (1)