Study of PM54 in Combination With Cytotoxic and Targeted Agents in Adult Participants With Advanced Malignancies

NCT07839819 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: PM54-A-004-26
• Study Type: interventional
• Target: 231
• Locations: 4 countries
• Sites: 9

Brief Summary

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.

Conditions

Advanced Solid Tumor

Keywords

Transcription inhibitor; Deoxyribonucleic acid; Antiproliferative effect; Antineoplastic; Pharmacokinetics

Outcome Measures

Primary Outcomes (3)

• 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 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)

  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.

  Baseline up to 5 years

Secondary Outcomes (10)

• Part 1 and 2: Clinical Benefit Rate (CBR)

  Up to 12 weeks

• Part 1 and 2: Confirmed ORR

  Baseline Up to 5 years

• Parts 1 and 2: Disease Control Rate (DCR)

  Baseline up to 5 years

• Parts 1 and 2: Progression-Free Survival

  Baseline up to 5 years

• Parts 1 and 2: Duration of Response

  Baseline to 5 years

Study Arms (4)

Part 1 (Dose Escalation) - PM54 + Irinotecan

EXPERIMENTAL

Participants will initially receive a low dose of PM54 in combination with a low dose of Irinotecan (sub- study 1). If the initial dose level is tolerated, the doses of PM54 and Irinotecan may be escalated to higher dose levels according to the study protocol until a suitable dose for the combination is established, or until clinical or objective disease progression, withdrawal of consent, or unacceptable or cumulative toxicity occurs.

Drug: PM54; Drug: Irinotecan

Part 1 (Dose Expansion) - PM54 + Irinotecan

EXPERIMENTAL

Participants will receive the recommended dose combination of PM54 and Irinotecan as identified in Part 1 of the study (sub- study 1).

Drug: PM54; Drug: Irinotecan

Part 2 (Dose Escalation) - PM54 + Doxorubicin

EXPERIMENTAL

Participants will initially receive a low dose of PM54 in combination with a low dose of Doxorubicin. If the initial dose level is tolerated, the doses of PM54 and Doxorubicin may be escalated to higher dose levels according to the study protocol until a suitable dose for the combination is established, or until clinical or objective disease progression, withdrawal of consent, or unacceptable or cumulative toxicity occurs.

Drug: PM54; Drug: Doxorubicin

Part 2 (Dose Expansion - PM54 + Doxorubicin

EXPERIMENTAL

Participants will receive the recommended dose combination of PM54 and Doxorubicin as identified in Part 1 of the study (sub - study 2).

Drug: PM54; Drug: Doxorubicin

Interventions

PM54 DRUG

Intravenous infusion.

Part 1 (Dose Escalation) - PM54 + Irinotecan; Part 1 (Dose Expansion) - PM54 + Irinotecan; Part 2 (Dose Escalation) - PM54 + Doxorubicin; Part 2 (Dose Expansion - PM54 + Doxorubicin

Irinotecan DRUG

Intravenous infusion.

Part 1 (Dose Escalation) - PM54 + Irinotecan; Part 1 (Dose Expansion) - PM54 + Irinotecan

Doxorubicin DRUG

Intravenous infusion.

Part 2 (Dose Escalation) - PM54 + Doxorubicin; Part 2 (Dose Expansion - PM54 + Doxorubicin

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 before the start of any study-specific procedures.
• Adults greater than or equal to (\>=) 18 years and able to provide free and informed consent for study participation.
• Have a pathologically confirmed diagnosis of 1 of the following (Tumor types have been omitted, as this information is not public.):
• Sub- study 1
• Tumor type, previously treated with 1 to 2 prior lines of therapy for advanced disease, which must have included at least 1 line of platinumbased chemotherapy and programmed cell death protein 1 inhibitor if locally available and approved. All histological subtypes are eligible.
• Tumor type, previously treated with 1 to 3 prior lines of therapy for advanced disease.
• Tumor type, previously treated with at least 1 but no more than 2 prior lines of chemotherapy.
• Sub- study 2
• Tumor type, with a maximum of 1 prior line of treatment for advanced disease, and tumor type in Part 2, with no prior treatment for advanced disease.
• Tumor type, with 2 or 3 prior lines of treatment for advanced disease, which must have included platinum-based chemotherapy and a programmed cell death protein-1 inhibitor. These may have been received as part of a single regimen or in separate regimens.
• Note: For the purpose of counting lines of therapy, regimens given as part of multi-modal treatment for localized tumor type (induction/consolidation) are considered 1 line of therapy if disease relapse has occurred during or up to 6 months following treatment discontinuation.
• Have an 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.
• Have a measurable disease according to RECIST v 1.1. Lesions in areas previously treated with radiation or ablative local therapies must, in addition to measurability requirements defined in RECIST v1.1, only be considered measurable if they experienced documented progression following local treatments.
• Have experienced objective disease progression on or following the last prior line of systemic therapy, as determined either by RECIST v1.1 or equivalent. This does not apply to first-line indications.
• Eastern cooperative oncology group (ECOG) performance status (PS) of 0 or 1 at screening.

You may not qualify if:

• To be eligible for trial participation, individuals must not meet any of the following criteria:
• Prior treatment with PM54 or any other ecteinascidin agent.
• History of hypersensitivity to PM54 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, low-risk and adequately treated prostate cancer, stage I hormone receptor (HR)-positive breast cancer or other in-situ disease at neglectable risk of relapse.
• Presence of carcinomatous meningitis.
• Participants with clinically significant ascites, defined as any of the following:
• Ascites requiring therapeutic paracentesis or medication (such as diuretics) in the last 4 weeks;
• Moderate or severe ascites on imaging;
• Symptomatic ascites (examples: abdominal distension, discomfort, or dyspnea).
• Presence of any of these medical conditions.
• Cardiovascular:
• History of myocardial, CNS, or other arterial infarction within 6 months before the start of study intervention.
• Heart failure Class II or higher according to the New York Heart Association or left ventricular ejection fraction less than (\<) 50 percent (%) per echocardiogram or multigated acquisition scan.
• Symptomatic arrhythmia or other significant electrocardiogram (ECG) abnormalities that in the opinion of the investigator pose an increased risk of complications.
• Corrected start of the Q wave to the end of the T wave interval (QTc) \>470 milliseconds (ms) on the screening ECG or history of a long QT syndrome.

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (9)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Institut Bergonie

Bordeaux, France

Location

Centre Leon Berard - Lyon

Lyon, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Helios Klinikum Berlin-Buch

Buckow, Germany

Location

Universitaetsmedizin Mainz

Mainz, Germany

Location

START Lisbon - ULS Santa Maria

Lisbon, Portugal

Location

Instituto Portugues De Oncologia Do Porto Francisco Gentil Epe Ipo Porto Ipopfg Clinica De Onco Hematologia

Porto, Portugal

Location

MeSH Terms

Interventions

Irinotecan; Doxorubicin

Intervention Hierarchy (Ancestors)

Camptothecin; Alkaloids; Heterocyclic Compounds; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Central Study Contacts

Gaston Federico Boggio, M.D

CONTACT

+34 91 823 4524; gfboggio@pharmamar.com

Study Design

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

Study Record Dates

• First Submitted: September 16, 2026
• First Posted: September 24, 2026
• Study Start (Estimated): November 12, 2026
• Primary Completion (Estimated): September 27, 2029
• Study Completion (Estimated): November 27, 2029
• Last Updated: September 24, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

PT (2); FR (3); DE (2); US (2)