The primary purpose of this study is to evaluate the safety, tolerability and recommended dose (RD) of PM54 in combination with cytotoxic and targeted anticancer agents in adult participants with advanced solid tumors. The study will also assess the antitumor activity of PM54 in combination with cytotoxic and targeted anticancer agents in terms of objective response rate (ORR) based on investigator's assessment in participants in other cohorts.
The main study will comprise several sub-studies evaluating PM54 in combination with different anticancer agents, starting with the following combinations: PM54 plus irinotecan and PM54 plus doxorubicin. Each sub-study includes Part 1 (Dose Escalation) and Part 2 (Dose Expansion). In Part 1, participants with advanced malignancies of selected tumor types will receive escalated doses of PM54 in combination with the relevant anticancer agent until a suitable dose is established, or until clinical or objective disease progression, withdrawal of consent, or unacceptable or cumulative toxicity occurs. In Part 2, participants with advanced malignancies will receive the recommended dose combination of PM54 and the relevant combination product identified during Part 1 of the corresponding sub-study.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
231
Intravenous infusion.
Intravenous infusion.
Intravenous infusion.
University of Nebraska Medical Center
Omaha, Nebraska, United States
The University of Texas MD Anderson Cancer Center
Houston, Texas, United States
Institut Bergonie
Bordeaux, France
Centre Leon Berard - Lyon
Lyon, France
Parts 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Treatment Discontinuation or Dose Modifications
Time frame: Time from the first administration of study intervention until 30 days after study intervention discontinuation or initiation of new subsequent anticancer therapy, whichever occurs first (up to 5 years)
Part 1: Number of Participants with Dose-Limiting Toxicities (DLTs)
Time frame: Cycle 1 (each cycle is of 21 days)
Part 2: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1
Percentage of participants who achieve a best overall response of complete response (CR) or partial response (PR), as determined by investigator assessment of tumor images according to RECIST v1.1. CR is defined as disappearance of all target lesions and all non-target lesions, with any pathological lymph nodes reduced to \<10 mm in short axis, and no new lesions. PR is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline, with no progression of non-target lesions and no new lesions.
Time frame: Baseline up to 5 years
Part 1 and 2: Clinical Benefit Rate (CBR)
Percentage of participants who achieve either an objective tumor response (CR or PR or stable disease) with an absence of tumor progression during the first 12 weeks, as determined by investigator assessment according to RECIST v1.1. CR is defined as disappearance of all target lesions, with any pathological lymph nodes reduced to \<10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum of diameters while on study. PD is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters while on study, with an absolute increase of at least 5 mm, or the appearance of one or more new lesions or unequivocal progression of existing non-target lesions.
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Centre Antoine Lacassagne
Nice, France
Helios Klinikum Berlin-Buch
Buckow, Germany
Universitaetsmedizin Mainz
Mainz, Germany
START Lisbon - ULS Santa Maria
Lisbon, Portugal
Instituto Portugues De Oncologia Do Porto Francisco Gentil Epe Ipo Porto Ipopfg Clinica De Onco Hematologia
Porto, Portugal
Time frame: Up to 12 weeks
Part 1 and 2: Confirmed ORR
Percentage of participants who achieve a confirmed objective response (CR or PR), as determined by investigator assessment according to RECIST v1.1. CR is defined as disappearance of all target lesions, with any pathological lymph nodes reduced to \<10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline. A response is considered confirmed when a subsequent assessment performed at least 4 weeks after the initial response confirms CR or PR.
Time frame: Baseline Up to 5 years
Parts 1 and 2: Disease Control Rate (DCR)
Percentage of participants who achieve a best overall response of stable disease, PR, or CR, as determined by investigator assessment according to RECIST v1.1. CR is defined as disappearance of all target lesions, with any pathological lymph nodes reduced to \<10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline. Stable disease is defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum of diameters while on study.
Time frame: Baseline up to 5 years
Parts 1 and 2: Progression-Free Survival
Time frame: Baseline up to 5 years
Parts 1 and 2: Duration of Response
Time frame: Baseline to 5 years
Parts 1 and 2: Time to Treatment Failure (TTF)
Time frame: Baseline up to 5 years
Parts 1 and 2: Overall Survival (OS)
Time frame: Baseline up to 5 years
Parts 1: Maximum Observed Plasma Concentration (Cmax) of PM54 and the Combination Product
Time frame: Cycle 1, Day 1 (each cycle is of 21 days)
Parts 1: Area Under the Plasma Concentration-Time Curve (AUC) of PM54 and the Combination Product
Time frame: Cycle 1, Day 1 (each cycle is of 21 days)
ORR per RECIST v1.1
Percentage of participants who achieve a best overall response of CR or PR, as determined by investigator assessment according to RECIST v1.1. CR is defined as disappearance of all target lesions, with any pathological lymph nodes reduced to \<10 mm in short axis. PR is defined as at least a 30% decrease in the sum of diameters of target lesions from baseline.
Time frame: Baseline Up to 5 Years