A Phase 2A Multicenter, Open Label Study of Promitil for the Treatment of Patients With Solid Tumors Associated With Deleterious Mutations Who Have Progressed After First Line Therapy

PROM-2301

This multicenter Phase 2a study was designed to evaluate the safety, tolerability, and efficacy of Promitil in patients with recurrent ovarian cancer and inoperable, locally advanced or metastatic pancreatic cancer, which bears deleterious germline or somatic mutations in BRCA1, BRCA2, or HRD (homologous recombination deficiency) -related genes. Based on reported preclinical and clinical efficacy of Mitomycin C in BRCA-mutated tumors, and together with the demonstrated improved safety profile of Promitil in humans, it is expected that this liposomal formulation will have a favorable therapeutic index and significant clinical antitumor activity in patients with tumors bearing BRCA 1/2 and/or PALB2 mutations.

2024-06-13

2026-06-01

2027-01-01

Recruiting

Early phase I

20

Inclusion Criteria: 1. 18 years of age or older on day of consent 2. Patient with either one of the following histologically or cytologically confirmed, deemed incurable malignancies: 1. Recurrent ovarian cancer 2. Inoperable, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC) 3. Patient with PDAC measurable by RECIST 1.1. Previously irradiated lesions may be considered measurable if there has been demonstrated progression in these lesions. Ovarian cancer patients can have either measurable or non-measurable lesions (i.e., ovarian cancer patients with mostly ascites or pleural effusion are eligible) 4. Tumor with a known pathogenic or likely pathogenic germline or somatic mutation in BRCA1, BRCA2 or HRD-related genes as determined by a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalently accredited laboratory. Note: Patients with positive HRD score can be eligible regardless of any evidence for germline or somatic mutations 5. Patient received at least 1 line of chemotherapy for advanced pancreatic adenocarcinoma or ovarian cancer. Prior neoadjuvant and adjuvant chemotherapy are allowed, and platinum re-challenge is allowed for ovarian cancer patients for whom it is felt to be in their best interests, as determined by the Investigator. Prior PARP inhibitor, hormonal, biological, or immunological therapy are allowed. Palliative radiation therapy is allowed, provided it was/will be completed ≥2 weeks prior starting trial therapy 6. Capable of providing written informed consent, which includes compliance with the requirements and restrictions listed in the consent form 7. ECOG performance status of 0 or 1 8. Adequate organ function as defined by: 1. Absolute neutrophil count (ANC) ≥ 1500/µL 2. Platelet count ≥ 100,000/µL 3. Hemoglobin ≥ 9 g/dL 4. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) 5. AST and ALT ≤ 3 x ULN OR ≤ 5 x ULN in the presence of liver metastases 6. Albumin ≥ 3g/dL 7. INR\<1.5 unless on anticoagulants 9. Creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 45 mL/minute (as calculated by the Cockcroft-Gault formula) 10. Estimated life expectancy of at least 3 months 11. Patients (men and women) of reproductive potential willing and able to use an acceptable method of birth control as approved by the PI 12. With the exception of alopecia and neuropathy, resolution of all acute toxic effects of any prior chemotherapy, surgery or radiotherapy to NCI CTCAE (Version 5.0) Grade ≤ 1 or to the baseline laboratory values as defined in Inclusion Criteria Number 8 and 9. Exclusion Criteria: 1. Uncontrolled intercurrent illness including, but not limited to, severe or ongoing active infection, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements 2. Any other severe concurrent disease which, in the judgment of the investigator, would make the subject unsuited for treatment 3. History of chronic active hepatitis, including carriage of hepatitis B virus (HBV) or hepatitis C virus (HCV), unless patient is adequately treated and shown to be serum virus-free 4. Evidence of active bleeding 5. Untreated brain metastases Note: Patients with brain metastases treated by surgery or radiation who are stable and symptom-free (≤ 4 mg dexamethasone/day) are eligible to participate in the study 6. Patient is pregnant or lactating 7. Prior intravenous treatment with MMC, either alone or in combination 8. Other anti-cancer treatment within 2 weeks before start of study drug 9. Other myelosuppressive treatment within 4 weeks before start of study drug 10. Treatment with other investigational drugs within 5 drug half-lives of day 1 of study drug

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'There will be 2 cohorts with up to 10 patients per cohort indication (ovarian/pancreatic). Eligible patients will be assigned in parallel to receive 6 cycles of Promitil treatment.', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 20, 'type': 'ESTIMATED'}}

2024-06-27