NCT04971499

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

Active, enrolled Phase 1, PHASE2 Last updated 20 February 2026

What this trial tests

Phase 1, PHASE2 trial testing Dapansutrile in Melanoma in 26 participants. Participants enrolled and being followed up; not accepting new ones.

Timeline

6 September 2022

Primary endpoint
30 April 2027

30 April 2027

Quick facts

Lead sponsor	April Salama, M.D.
Phase	Phase 1, PHASE2
Status	Active, enrolled
Study type	INTERVENTIONAL
Allocation	non randomized
Design	sequential
Masking	none
Primary purpose	treatment
Enrollment	26
Start date	6 September 2022
Primary completion	30 April 2027
Estimated completion	30 April 2027
Sites	1 location across United States

Drugs / interventions tested

• Dapansutrile — full drug profile →
• Pembrolizumab (pembrolizumab) — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →

Sponsor

April Salama, M.D.

Who can join

18 and older, any sex, with Melanoma. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. NLRP3 and cancer: Pathogenesis and therapeutic opportunities.
   Tengesdal IW, Dinarello CA, Marchetti C. · · 2023 · cited 37× · PMID 37866732 · DOI 10.1016/j.pharmthera.2023.108545
2. Sphingolipid metabolism and complement signaling in cancer progression.
   Janneh AH, Atkinson C, Tomlinson S, Ogretmen B. · · 2023 · cited 26× · PMID 37507302 · DOI 10.1016/j.trecan.2023.07.001
3. Screening NLRP3 drug candidates in clinical development: lessons from existing and emerging technologies.
   Tengesdal IW, Banks M, Dinarello CA, Marchetti C. · · 2024 · cited 21× · PMID 39188718 · DOI 10.3389/fimmu.2024.1422249
4. Overcoming Immunotherapy Resistance by Targeting the Tumor-Intrinsic NLRP3-HSP70 Signaling Axis.
   Theivanthiran B, Haykal T, Cao L, Holtzhausen A, et al · · 2021 · cited 14× · PMID 34638239 · DOI 10.3390/cancers13194753
5. Shaping the Future of Immunotherapy Targets and Biomarkers in Melanoma and Non-Melanoma Cutaneous Cancers.
   Spiliopoulou P, Vornicova O, Genta S, Spreafico A. · · 2023 · cited 10× · PMID 36674809 · DOI 10.3390/ijms24021294
6. Diverse functions of NLRP3 inflammasome in PANoptosis and diseases.
   Jiang Y, Qiang Z, Liu Y, Zhu L, et al · · 2025 · cited 6× · PMID 40830103 · DOI 10.1038/s41420-025-02689-1
7. The NLRP3 Inflammasome: Mechanisms of Activation, Regulation, and Therapeutic Opportunities.
   Zou C, Jiang S, Li H, Zhao K, et al · · 2026 · PMID 41799937 · DOI 10.1002/mco2.70660
8. Impact of KRAS mutation subtypes on morphological heterogeneity and immune landscape in surgically treated lung adenocarcinoma.
   Torok K, Ferencz B, Boettiger K, Pozonec MD, et al · · 2025 · PMID 40673097 · DOI 10.21037/tlcr-2024-1092