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MelanomaPhase 1/2NCT04971499

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

A Phase 1/2 study testing Dapansutrile and Pembrolizumab in people with Melanoma, run by April Salama, M.D. at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Melanoma
What is being tested?
Dapansutrile and Pembrolizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
26 participants
Where
1 siteUnited States
Study dates
6 Sep 2022to 30 Apr 2027
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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)
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  • 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.
  • 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.
  • Patients who progress while receiving or within 6 months of receiving the last dose of anti-PD-1/L1 mAb in the neoadjuvant or adjuvant setting will be included. Inclusion of patients who progress within 6 months of stopping neoadjuvant or adjuvant anti-PD-1/L1 mAb will be capped at 20% of the total study population. Inclusion of patients who progress while still receiving neoadjuvant or adjuvant anti-PD-1/L1 mAB will not be capped.
  • 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
  • Multiple target lesions will be allowed and will be selected based on standard RECIST criteria.
  • The following cutaneous lesions will be considered measurable lesions: lesions ≥ 10 mm in longest diameter or multiple melanoma lesions which in aggregate have a longest diameter of ≥ 10 mm, when measured by caliper.
  • Have available archival tumor tissue sample or newly obtained core or excisional biopsy of a tumor lesion. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slides.
  • Newly obtained biopsies are preferred to archived tissue, but archived sample can be used at baseline provided that the patient has only had anti-PD-1/L1 based regimen since obtaining the sample.
  • Biopsies may be taken from any amenable lesion, but it is preferable to use the same lesion throughout.
  • Biopsy may be taken from previously irradiated lesions only if they have progressed since radiation therapy.
  • Patient may still be eligible for study if tumor is not amenable to safe biopsy or biopsy is judged by patient or treating physician to not be in their best interest.
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2. Evaluation of ECOG must be performed within 7 days prior to C1D1.
  • Adequate organ function as defined below. Specimens must have been collected within 7 days prior to the start of study treatment:
  • Absolute neutrophil count (ANC) ≥1500/µL
  • Platelets ≥100,000/µL
  • Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/La
  • Creatinine OR measured or calculated creatinine clearance (GFR can be used in place of CrCl) ≤1.5 x ULN OR ≥45 mL/min for participant with creatinine levels >1.5 x institutional ULN
  • Total bilirubin ≤1.5 x ULN OR direct bilirubin ≤ULN for participants with total bilirubin levels > 1.5 x ULN
  • AST (SGOT) and ALT (SGPT) ≤2.5 x ULN (≤5 x ULN for participants with liver metastases)
  • International normalized ratio (INR) OR prothrombin time (PT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
  • Activated partial thromboplastin time (aPTT) ≤1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants NOTE: Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within the last 2 weeks NOTE: Creatinine clearance (CrCl) should be calculated per institutional standard
  • Prior adverse events from anticancer therapy must be resolved to ≤ grade 1, with the exception of alopecia or endocrinopathies, which may be on replacement therapy. Prednisone equivalent of ≤ 10 mg is allowed.

Who cannot join

  • 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
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  • 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
  • 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
  • Known history of Human Immunodeficiency Virus (HIV) infection
  • Known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection. Note: no testing for Hepatitis B and Hepatitis C is required
  • Has a known history of active TB (Bacillus Tuberculosis)
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Expecting to conceive or father children within the projected duration of study participation, starting with the screening visit through 120 days after the last dose of trial treatment
  • History of allogenic tissue/solid organ transplant

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Duke Cancer Center

    Durham, North Carolina, 27710

Other trials in United States

About this study

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
Being tested
Dapansutrile, Pembrolizumab
Medical subject headings
Melanoma

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • DapansutrileDrug

    500 mg tablet

  • PembrolizumabDrug

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

Study groups in NCT04971499
Study groupRoleWhat they receive
Dose SelectionExperimentalDapansutrile 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.
Receives: Drug: Dapansutrile; Drug: Pembrolizumab
Dose ExpansionExperimentalDapansutrile at the RP2D plus Pembrolizumab 200 mg IV every three weeks
Receives: Drug: Dapansutrile; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 90 days after last dose

  2. 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.

    Measured: Up to 2 years

Secondary outcomes (4)

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

    Measured: after 6 months

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

    Measured: after 12 months

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

    Measured: after 6 months

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

    Measured: after 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Jul 2021
  2. Study start6 Sep 2022
  3. Primary completion30 Apr 2027 (estimated)
  4. Study completion30 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
26 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04971499
Sponsor's protocol ID
Pro00108864
Status last verified
Nov 2026
First submitted
12 Jul 2021
Last updated
6 Nov 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified data may be shared with supporting companies and aggregate data will be included in the final publication.

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Dapansutrile and Pembrolizumab in people with Melanoma, run by April Salama, M.D. at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 34 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of AEs (including SAEs and DLTs) as measured by patient interview and medical record review (time frame: 90 days after last dose). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04971499.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.

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