Description:
PROMIT is a single arm phase 2 trial evaluating the clinical activity of immune checkpoint
blockade (ICB) after administration of dacarbazine (DTIC) in patients with unresectable or
metastatic, BRAF wildtype melanoma with primary resistance to anti-programmed-cell-death-1
(PD-1/PD-L1) or PD-1 plus anti-cytotoxic-T-lymphocyte antigen 4 (CTLA-4) blockade therapy. If
the activity is clinically meaningful, DTIC could become a new therapeutic option to break
primary resistance to immunotherapy.
Title
- Brief Title: Preconditioning of Tumor, Tumor Microenvironment and the Immune System to Immunotherapy
- Official Title: A Phase 2, Single Arm Study on Dacarbazine (DTIC) Followed by Immunotherapy Re-challenge in Unresectable or Metastatic Melanoma With Primary Resistance to PD-1/PD-L1 or PD-1 + CTLA-4 Blockade
Clinical Trial IDs
- ORG STUDY ID:
PROMIT
- NCT ID:
NCT04225390
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Dacarbazine (DTIC) | DTIC | Dacarbazine |
Purpose
PROMIT is a single arm phase 2 trial evaluating the clinical activity of immune checkpoint
blockade (ICB) after administration of dacarbazine (DTIC) in patients with unresectable or
metastatic, BRAF wildtype melanoma with primary resistance to anti-programmed-cell-death-1
(PD-1/PD-L1) or PD-1 plus anti-cytotoxic-T-lymphocyte antigen 4 (CTLA-4) blockade therapy. If
the activity is clinically meaningful, DTIC could become a new therapeutic option to break
primary resistance to immunotherapy.
Detailed Description
PROMIT is a phase 2, single arm, open label study of DTIC followed by combined immune
checkpoint blockade (ICB) therapy or PD-1/PD-L1-blockade monotherapy in adult (≥ 18 years)
subjects with previously treated, unresectable or metastatic melanoma (Stage III or Stage IV
melanoma as per the AJCC staging system). Subjects must be BRAF wildtype and must have shown
primary resistance to ICB. Fresh tumor tissue from an unresectable or metastatic site of
disease must be available.
Subjects will be treated with DTIC 850 mg/m² day 1 and 21 i.v. (DTIC phase). Afterwards,
patients will receive combined ipilimumab (3 mg/kg) and nivolumab (1 mg/kg) 4 times every 3
weeks i.v. OR nivolumab 240 mg every 2 weeks OR pembrolizumab 200 mg every 3 weeks (ICB
re-exposure phase; EMA-approved dosing scheme). By the end of the ICB phase, response will be
documented (primary endpoint). A safety follow-up for treatment-related adverse events will
be performed until 30 days after the last dose of combined ICB. Patients will be followed for
survival every 12 weeks after the end of the combined ICB phase (second primary endpoint).
Tumor and blood samples will be assessed over the course of the study to evaluate changes in
tumor, tumor microenvironment and immune system.
Trial Arms
Name | Type | Description | Interventions |
---|
Dacarbazine | Experimental | Dacarbazine (day1 and day21) 850 mg/m² i.v. followed by re-exposure to the previous immunotherapy | |
Eligibility Criteria
Inclusion Criteria:
1. Histologically confirmed metastatic melanoma
2. Progression after checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade)
3. Accessible tumor metastases
4. ECOG 0 or 1
5. Adequate organ function
Exclusion Criteria:
1. Uvea melanoma, mucosal melanoma
2. Previous chemotherapy in metastatic disease
3. Previous response to checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4
blockade) in metastatic disease
4. BRAF V600 mutation
5. Active brain metastases
6. Autoimmune disease requiring more than 10 mg prednisolone daily or other
immunosuppressive drugs
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Rate of participents with CR, PR, SD or PD |
Time Frame: | week 14 |
Safety Issue: | |
Description: | A patient is defined as responder if a complete response (CR) or partial response (PR) can be seen. A patient with stable disease (SD) or progressive disease (PD) will be defined as non-responder. |
Secondary Outcome Measures
Measure: | Overall survival (OS) |
Time Frame: | up to 5 years |
Safety Issue: | |
Description: | Overall survival (OS), defined as the time between study inclusion and date of death (any cause). For subjects without documentation of death, OS will be censored on the last date the subject was known to be alive. OS will be followed continuously while subjects are on the study drug and every 12 weeks via phone contact after subjects discontinue the treatment phase. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Erlangen-Nürnberg Medical School |
Trial Keywords
- immune checkpoint blockade
- resistance
- dacarbazine
Last Updated
January 14, 2021