Preconditioning of Tumor Tumor Microenvironment and the Immune System to Immunotherapy

  • STATUS
    Recruiting
  • End date
    Jul 29, 2023
  • participants needed
    38
  • sponsor
    University of Erlangen-Nürnberg Medical School
Updated on 29 January 2021

Summary

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.

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/m 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.

Details
Condition Immunotherapy, immunotherapies
Treatment Dacarbazine (DTIC)
Clinical Study IdentifierNCT04225390
SponsorUniversity of Erlangen-Nürnberg Medical School
Last Modified on29 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Histologically confirmed metastatic melanoma
Progression after checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade)
Accessible tumor metastases
ECOG 0 or 1
Adequate organ function

Exclusion Criteria

Uvea melanoma, mucosal melanoma
Previous chemotherapy in metastatic disease
Previous response to checkpoint inhibitor therapy (PD-1/PD-L1 or PD-1 + CTLA-4 blockade) in metastatic disease
BRAF V600 mutation
Active brain metastases
Autoimmune disease requiring more than 10 mg prednisolone daily or other immunosuppressive drugs
Clear my responses

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