Clinical Trial of PM54 in Advanced Solid Tumors Patients.

NCT05841563 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PM54-A-001-222023-508644-22-00
• Study Type: interventional
• Target: 125
• Locations: 3 countries
• Sites: 3

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (12)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Dose-limiting toxicities (DLTs)

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Treatment-emergent Adverse Events (TEAEs)

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Drug-related Adverse Events (AEs)

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Drug-related deaths

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Serious adverse events (SAEs)

  Screening up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Drug-related delays

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Dose reductions

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Treatment discontinuations

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Maximum tolerated dose (MTD)

  Lowest dose level explored during dose escalation in which one third (i.e., 33%) or more of evaluable patients develop a DLT in Cycle 1.

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1a (dose escalation) and Phase1b (safety run-in): Recommended dose (RD)

  Once the maximum tolerated dose (MTD) is reached, lower dose level will be confirmed as the RD if less than one third (i.e., 33%) of at least nine fully evaluable patients at that dose level develop DLT during Cycle 1.

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase1b (safety run-in): Determination of RD with more extensive premedication

  A dose level will be confirmed as the RD with more extensive premedication if less than one third (i.e., 33%) of at least nine fully evaluable patients at that dose level develop DLT during Cycle 1.

  Day 1 Cycle 1 up to end of first cycle of treatment (Cycle 1 is 21 days)

• Phase 1b (expansion): Antitumor activity

  Antitumor activity, evaluated according to the RECIST v.1.1 (or mRECIST v.1.1 in case of MPM) and serum markers, as appropriate.

  Every 6 weeks (± 1 week) in all patients with evaluable disease until Cycle 6. For patients continuing treatment after Cycle 6, assessments performed every 9 weeks (± 1 week) while on treatment, unless otherwise indicated (Up to 48 months)

Secondary Outcomes (13)

• Phase 1b (expansion): Adverse events (AEs)

  Screening to end of study (up to approximately 48 months)

• Phase 1b (expansion): Treatment discontinuation

  Day 1 up to end of study (up to approximately 48 months)

• Phase 1b (expansion): Dose reductions

  Day 1 up to end of study (up to approximately 48 months)

• Phase 1b (expansion): Treatment delays due to adverse events (AEs)

  Day 1 up to end of study (up to approximately 48 months)

• Phase 1a (dose escalation) and Phase 1b (safety run-in): QT Assessment

  Day 1 of Cycle 1 for all patients participating in the QT assessment, and on Day 1 of Cycle 2 for patients treated during the Phase Ia stage once the MTD has been determined, will be used in this substudy.

Study Arms (1)

PM54

EXPERIMENTAL

Phase Ia (dose escalation) stage: Patients will receive PM54 i.v. at a starting dose of 0.3 mg/m2. Phase Ib (safety run-in) stage: The maximum tolerated dose (MTD) of PM54 previously defined in Phase Ia will be reassessed. Phase Ib (expansion) stage: Patients will receive PM54 i.v. at the recommended dose selected after the safety run-in stage.

Drug: PM54

Interventions

PM54 DRUG

PM54 powder for concentrate for solution for infusion (3 mg/vial) is a sterile, preservative-free, lyophilized white to yellowish cake in a single-dose vial for reconstitution prior to intravenous infusion. Each vial contains 3 mg PM54. Route of administration: Intravenous infusion

PM54

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• Genitourinary tract tumors: urothelial carcinoma, clear cell renal carcinoma and prostate adenocarcinoma.
• Cutaneous melanoma.
• Gastrointestinal: esophageal adenocarcinoma, gastric adenocarcinoma, pancreatic adenocarcinoma, and poorly differentiated (grade 3) gastroenteropancreatic Neuroendocrine Carcinoma (NEC )with Ki67 index \>55%.
• Lung: non-small cell lung cancer (NSCLC) and Small Cell Lung Cancer (SCLC).
• Gynecological tumors: epithelial ovarian carcinoma (including primary peritoneal disease and/or fallopian tube carcinomas), endometrial adenocarcinoma and carcinoma of cervix.
• Breast: ductal or lobular.
• Sarcoma: liposarcoma, leiomyosarcoma, synovial sarcoma and Ewing sarcoma.
• Deleterious germline BRCA1/2 mutation tumors.
• Other: MPM, extrapulmonary small cell carcinoma, adrenocortical carcinoma.
• 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.

You may not qualify if:

• For both stages:
• Concomitant diseases/conditions:
• Increased cardiac risk:
• Uncontrolled arterial hypertension despite optimal management (≥160/100 mmHg).
• Presence of clinically relevant valvular disease.
• History of long QT syndrome.
• Corrected QT interval (QTcF, Fridericia correction) ≥450 ms on screening ECG.
• History of ischemic heart disease, including myocardial infarction, unstable angina, coronary arteriography or cardiac stress testing with findings consistent with coronary occlusion or infarction ≤6 months prior to study entry.
• History of heart failure or left ventricular dysfunction (left ventricular ejection fraction \[LVEF\] ≤50%) by multiple-gated acquisition scan (MUGA) or echocardiography (ECHO).
• Clinically relevant ECG abnormalities, including any of the following: right bundle branch block with left anterior hemiblock, second (Mobitz II) or third degree atrioventricular block.
• Symptomatic arrhythmia.
• Concomitant medication with risk of inducing torsades de pointes, which cannot be discontinued or switched to an alternative drug prior to start PM54 dosing.
• Use of a cardiac pacemaker.
• 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.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (3)

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229-3307, United States

RECRUITING

Institut Jules Bordet

Anderlecht, 1070, Belgium

RECRUITING

HM Universitario Sanchinarro

Madrid, M, 28050, Spain

RECRUITING

Central Study Contacts

Cristian M Fernández, M.D.

CONTACT

+ 34 91 846 6077; cmfernandez@pharmamar.com

Gaston Federico Boggio, M.D.

CONTACT

+34 91 823 4524; gfboggio@pharmamar.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2023
• First Posted: May 3, 2023
• Study Start: April 28, 2023
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: September 24, 2025

Record last verified: 2025-09

Locations

BE (1); US (1); ES (1)