Study of PM54 in Combination With Immunotherapy in Adult Participants With Advanced Malignancies
ConditionAdvanced Malignancies
Trial statusRecruiting
Trial phasePhase 1, Phase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorPharmaMar
About this trial
The main purpose of the study is to evaluate the safety, tolerability and recommended dose of PM54 in combination with pembrolizumab. To assess the antitumor activity of PM54 in combination with pembrolizumab in terms of clinical benefit rate (CBR) and objective response rate (ORR) based on investigator's assessment in participants in other cohorts.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Voluntarily signed and dated written informed consent, obtained before the start of any study-specific procedures.
Adults (greater than or equal to [>=]18 years or legal consenting age, per local regulations), and able to provide free and informed consent for study participation.
Have a pathologically confirmed diagnosis of advanced malignancy.
Have advanced disease, as defined by progressive, relapsed, or metastatic disease that is not amenable to multimodal ablative or excisional treatments with curative intent, according to international guidelines.
Disqualifiers
Prior treatment with PM54 or any other ecteinascidin agent, including ecubectedin, trabectedin, and lurbinectedin.
History of hypersensitivity to PM54, pembrolizumab, or any of the inactive ingredients.
History of other malignancies within 3 years prior to start of study intervention, except adequately resected non-melanoma skin cancer or other in-situ disease at neglectable risk of relapse.
Presence of carcinomatous meningitis.
Trial design
Design model
Sequential
Treatments tested in this trial
Pembrolizumab
DrugIntravenous infusion.
PM54
DrugIntravenous infusion.
Treatment groups
119 Participants
are divided into 2 treatment groupsGroup A: Part 1 (safety Run-in): PM54 + PembrolizumabExperimental treatment 2 interventions
Group B: Part 2 (Dose Expansion): PM54 + PembrolizumabExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Parts 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Treatment Discontinuation
Time frame
From signing of the informed consent up to 30 days after last dose (up to 3 years)2
Part 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
Time frame
Cycle 1 (each cycle is of 21 days)3
Part 2: Clinical Benefit Rate
CBR is defined as the percentage of participants who achieve either an objective tumor response - complete response (CR), partial response (PR) - or confirmed stable disease with an absence of tumor progression during the first 12 weeks. CBR was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST) v1.1. CR: Disappearance of all non-nodal target lesions and reduction in short axis of pathological lymph nodes to less than (\<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression disease (PD).
Time frame
up to 12 weeks4
Part 2: Objective Response Rate
ORR is defined as the percentage of participants who achieve complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 as determined by the Investigator. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions.
Time frame
Baseline up to 3 yearsSecondary outcomes
1
Parts 1 and 2: Confirmed Objective Response Rate
Confirmed ORR is defined as a best objective response (OR) of CR or PR according to mRECIST v1.1 and determined by Investigator. CR: Disappearance of all non-nodal target lesions and reduction in short axis of pathological lymph nodes to \< 10 mm; PR: at least a 30% decrease in the sum of diameters of target lesions from baseline.
Time frame
Baseline up to 3 years2
Part 1: Clinical Benefit Rate
CBR is defined as the percentage of participants who achieve either an objective tumor response - complete response (CR), partial response (PR) - or confirmed stable disease with an absence of tumor progression during the first 12 weeks. CBR was assessed according to mRECIST v1.1 and determined by Investigator. CR: Disappearance of all non-nodal target lesions and reduction in short axis of pathological lymph nodes to less than (\<) 10 millimeter (mm); PR: at least a 30 percent (%) decrease in the sum of diameters of target lesions from baseline; SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progression disease (PD).
Time frame
up to 12 weeks3
Parts 1 and 2: Disease Control Rate (DCR)
DCR defined as the percentage of participants who achieve a best overall response of CR, PR and SD according to RECIST v1.1 and determined by Investigator. CR: defined as disappearance of all target and all non-target lesions and no new lesions. PR: defined as at least a 30% decrease in sum of diameters of target lesions, taking as reference the baseline sum diameters, no progression of non-target lesions and no new lesions. SD: SD: reduction in sum of diameters of target lesions of 10% or greater, confirmed on a subsequent scan.
Time frame
Baseline up to 3 years4
Parts 1 and 2: Progression-free survival (PFS)
Time frame
Baseline up to 3 years Source ClinicalTrials.gov