Preconditioning of Tumor, Tumor Microenvironment and the Immune System to Immunotherapy (PROMIT)

University of Erlangen-Nürnberg Medical School

Status and phase: Unknown; Phase 2

Conditions: Immunotherapy

Treatments: Drug: Dacarbazine (DTIC)

Study type: Interventional

Funder types: Other

Identifiers

NCT04225390

PROMIT

Details and patient eligibility

About

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.

Full 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.

Enrollment: 38 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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38 participants in 1 patient group

Dacarbazine

Experimental group

Description:

Dacarbazine (day1 and day21) 850 mg/m² i.v. followed by re-exposure to the previous immunotherapy

Treatment:

Drug: Dacarbazine (DTIC)