Status and phase
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Study type
Funder types
Identifiers
About
The first part of the study (phase Ia - dose escalation) will evaluate the safety and tolerability and identify the dose-limiting toxicities (DLTs) of PM54.
The second part of the study (phase Ib - safety run-in and expansion) will be to reassess the maximum tolerated dose (MTD) defined in the Phase Ia stage in a framework of more extensive premedication, and to evaluate the antitumor activity of PM54 according to the RECIST v.1.1 (or mRECIST v.1.1 in case of MPM) and/or serum markers as appropriate, in patients with selected advanced solid tumors.
Enrollment
Sex
Ages
Volunteers
Inclusion criteria
Voluntarily signed and dated written informed consent, obtained prior to any specific study procedure.
Age ≥18 years.
Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1.
Phase Ia (dose escalation) stage: patients must have:
Pathologically confirmed diagnosis of advanced solid tumors for whom no standard therapy exists:
Note: patients with measurable or non-measurable disease according to the Response Evaluation Criteria In Solid Tumors (RECIST) v.1.1 (or mRECIST v.1.1 in case of MPM) are eligible during this stage.
No more than three prior lines of chemotherapy.
Phase Ib (safety run-in and expansion) stage: patients must have:
Pathologically confirmed diagnosis of one of the following:
Measurable disease according to the RECIST v.1.1 (or mRECIST v.1.1 in case of MPM) and/or evaluable disease byserum markers in case of prostate and ovarian cancer (according to the Prostate-Specific Antigen Working Group Recommendations (PSAWGR) and the Gynecologic Cancer Intergroup (GCIG) specific criteria, respectively).
Progressive disease after last therapy at study entry.
Patients must have received standard treatments:
Extrapulomnary small cell carcinoma/ gastroenteropancreatic NEC: no more than two prior lines of chemotherapy.
Cutaneous melanoma:
Malignant pleural mesothelioma (MPM): no more than two prior lines of therapy; one of them should be a platinum containing line. Patients with non-epithelioid MPM should have received a prior immunotherapy line.
Endometrial adenocarcinoma: no more than two prior lines of chemotherapy for metastatic disease. In addition, regardless of setting, patients must have received one prior platinum-containing regimen.
Synovial sarcoma: at least one but no more than two prior lines of chemotherapy.
Recovery to grade ≤1 from drug-related AEs of previous treatments, excluding grade 2 alopecia, according to the NCI-CTCAE v.5.
Laboratory values within seven days prior to first infusion:
Washout periods:
Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure during the course of the trial and up to seven months after the last study drug infusion. Fertile male patients with WOCBP partners should use condoms during treatment and for four months following the last study drug infusion.
Exclusion criteria
For both stages:
Concomitant diseases/conditions:
Increased cardiac risk:
Active infection requiring systemic treatment.
Known human immunodeficiency virus (HIV) or known chronic active hepatitis. For Hepatitis B, this includes positive tests for both Hepatitis B surface antigen and quantitative Hepatitis B polymerase chain reaction (PCR). For Hepatitis C, this includes positive tests for both Hepatitis C antibody and quantitative Hepatitis C PCR.
Any other major illness that, in the Investigator's judgment, will substantially increase the risk associated with the patient's participation in this study (e.g., COVID-19).
Symptomatic, steroid-requiring, and progressing central nervous system (CNS) disease. Exceptions will be made for patients who have completed radiotherapy at least four weeks prior to inclusion (asymptomatic patients taking steroids in the process of already being tapered within two weeks prior to inclusion).
Patients with carcinomatous meningitis.
Prior bone marrow or stem cell transplantation.
Prior treatment with trabectedin, lurbinectedin, or ecubectedin (PM14).
Use of (strong or moderate) inhibitors or strong inducers of CYP3A4 activity within two weeks prior to the first infusion of PM54.
Known hypersensitivity to any of the components of the drug product.
Limitation of the patient's ability to comply with the treatment or to follow the protocol procedures.
Women who are pregnant or breast feeding and fertile patients (men and women) who are not using a highly effective method of contraception (see inclusion criterion No. 9).
Primary purpose
Allocation
Interventional model
Masking
125 participants in 1 patient group
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Central trial contact
Gaston Federico Boggio, M.D.; Cristian M Fernández, M.D.
Data sourced from clinicaltrials.gov
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