Study of PM54 in Combination With Immunotherapy in Adult Participants With Advanced Malignancies

NCT07644039 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: PM54-A-003-252025-523774-16
• Study Type: interventional
• Target: 119
• Locations: 1 country
• Sites: 6

Brief Summary

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.

Conditions

Advanced Malignancies

Outcome Measures

Primary Outcomes (4)

• Parts 1 and 2: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious TEAEs and TEAEs Leading to Treatment Discontinuation

  From signing of the informed consent up to 30 days after last dose (up to 3 years)

• Part 1: Number of Participants with Dose-Limiting Toxicities (DLTs)

  Cycle 1 (each cycle is of 21 days)

• 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).

  up to 12 weeks

• 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.

  Baseline up to 3 years

Secondary Outcomes (9)

• Parts 1 and 2: Confirmed Objective Response Rate

  Baseline up to 3 years

• Part 1: Clinical Benefit Rate

  up to 12 weeks

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

  Baseline up to 3 years

• Parts 1 and 2: Progression-free survival (PFS)

  Baseline up to 3 years

• Parts 1 and 2: Duration of Response (DoR)

  Baseline up to 3 years

Study Arms (2)

Part 1 (safety Run-in): PM54 + Pembrolizumab

EXPERIMENTAL

Participants will initially receive a low dose of PM54. If the low dose level is tolerated, PM54 will be escalated to the high dose level in combination with pembrolizumab until a suitable dose of PM54 is established or until clinical or objective disease progression, withdrawal of consent, or unacceptable or cumulative toxicity occurs.

Drug: Pembrolizumab; Drug: PM54

Part 2 (Dose Expansion): PM54 + Pembrolizumab

EXPERIMENTAL

Participants will receive recommended dose of PM54 in combination with pembrolizumab as observed in Part 1 of the study.

Drug: Pembrolizumab; Drug: PM54

Interventions

Pembrolizumab DRUG

Intravenous infusion.

Part 1 (safety Run-in): PM54 + Pembrolizumab; Part 2 (Dose Expansion): PM54 + Pembrolizumab

PM54 DRUG

Intravenous infusion.

Part 1 (safety Run-in): PM54 + Pembrolizumab; Part 2 (Dose Expansion): PM54 + Pembrolizumab

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 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.
• Have measurable disease according to RECIST1.1 (or mRECIST v1.1 where applicable).
• Have experienced objective disease progression on or following the prior line(s) of systemic therapy, as determined either by (1) RECIST v1.1 or equivalent, or (2) by investigator's assessment of clinical progression of disease together with objective evidence of increased tumor burden even if not meeting criteria for progressive disease per RECIST v1.1 or equivalent.
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 or 1 at screening.
• Individuals with central nervous system (CNS) metastases are eligible, as long as all of the following are met:
• Asymptomatic or minimally symptomatic and stable, with no worsening symptoms in the 4 weeks prior to start of study intervention.
• Does not require systemic corticosteroids in excess of an equivalent prednisone dose of 5 milligrams per day (mg/day).
• Has undergone surgery or radiation and recovered of the effects thereof or are undergoing active surveillance for small-volume CNS metastases with no immediate risk of worsening. A minimum of 2 weeks must have elapsed between the end of whole-brain radiation treatment and study intervention.
• Have not had an epileptic seizure within the 4 weeks prior to start of anticancer treatment and are either free of antiepileptics or on a stable dose prescribed as prophylaxis.
• Adequate laboratory parameters, as specified below, within 7 days of start of study intervention:
• Absolute neutrophil count (ANC) \>=1.5\*10\^9 per liter, platelet count \>=100\*10\^9 per liter, and hemoglobin \>=9 gram per deciliter (g/dL).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to \[\<=\] 3.0\*the upper limit of normal (ULN).

You may not qualify if:

• 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.
• 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 \<45 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 QT interval (QTc) \>470 milliseconds (ms) on the screening ECG or history of a long QT syndrome.
• Respiratory
• History of interstitial lung disease (ILD) or pneumonitis that have required steroids or other forms of immunosuppression, or any ongoing or suspicion of ILD.
• Severe underlying lung disorder, as per investigator's assessment that can include but not restricted to chronic obstructive pulmonary disease, asthma, restrictive lung disease, or significant pleural effusions not related to the study condition.
• New onset or worsening of pulmonary embolism or deep vein thrombosis within the previous 2 months, or any history thereof if no stable dose of anticoagulant regimen has been achieved.
• Other

Sponsors & Collaborators

• PharmaMar: lead

Study Sites (6)

START New York

New York, New York, 11042, United States

NOT YET RECRUITING

START Dallas

Fort Worth, Texas, 76104, United States

RECRUITING

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

NEXT Houston

Houston, Texas, 77054, United States

RECRUITING

NEXT Dallas

Irving, Texas, 75039, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

NOT YET RECRUITING

Related Publications (1)

• Armato SG 3rd, Nowak AK. Revised Modified Response Evaluation Criteria in Solid Tumors for Assessment of Response in Malignant Pleural Mesothelioma (Version 1.1). J Thorac Oncol. 2018 Jul;13(7):1012-1021. doi: 10.1016/j.jtho.2018.04.034. Epub 2018 May 9.

  PMID: 29753121 BACKGROUND

MeSH Terms

Interventions

pembrolizumab

Central Study Contacts

Cristian Fernandez, M.D.

CONTACT

0034 91 846 6077; cmfernandez@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: June 8, 2026
• First Posted: June 12, 2026
• Study Start: May 21, 2026
• Primary Completion (Estimated): April 2, 2029
• Study Completion (Estimated): April 2, 2029
• Last Updated: June 12, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (6)