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Advanced MalignanciesPhase 1/2NCT07644039

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

A Phase 1/2 study testing Pembrolizumab and PM54 in people with Advanced Malignancies, run by PharmaMar at 11 sites in 2 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Advanced Malignancies
What is being tested?
Pembrolizumab and PM54
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
119 participants
Where
11 sitesin 2 countries
Study dates
21 May 2026to 2 Apr 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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).
  • Total bilirubin <=1.0*ULN; up to 1.5*ULN for participants with Gilbert's syndrome.
  • Creatinine clearance >=30 milliliter per minute (mL/min), calculated using the Cockcroft and Gault's formula.
  • Serum albumin >=3 g/dL. Albumin infusion to increase the blood level in order to fulfill this inclusion criterion is strictly forbidden.
  • Creatine kinase <=2.5*ULN.
  • Recovered from the effects of any prior surgery or radiation.
  • No ongoing toxicities from prior anticancer treatment of Grade >1 (per National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) verison6.0), except for alopecia and other Grade 2 toxicities that are considered by the investigator to have stabilized/resolved with sequelae and are not at risk of worsening with study intervention. Residual Grade 1 to 2 toxicities from prior immunotherapy -which may include hypo- or hyperthyroidism, type 1 diabetes, hyperglycemia, and adrenal insufficiency - are allowed, if stable and on a stable dose of replacement therapy as applicable.
  • Is willing to undergo trial procedures as specified in the protocol, including provision of biologic samples, as well as any study restrictions.
  • Evidence of non-childbearing status for women of childbearing potential (WOCBP). WOCBP must agree to use a highly effective contraceptive measure during the course of the trial and up to 7 months after the last study intervention infusion. Fertile male participants with WOCBP partners should use condoms during treatment and for 4 months following the last study intervention infusion.

Who cannot join

  • 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:
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  • 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
  • History of autoimmune or connective tissue disease that (a) in the opinion of the investigator may have a significant risk of worsening with study intervention or (b) has a history or risk of significant mg/day of prednisone equivalent or other systemic immunosuppressants in the previous 1 year to control a disease flare.
  • Uncontrolled infection requiring antimicrobial agents or unexplained fever within 3 days of the first scheduled day of dosing. Participants with tumor fever may be enrolled if infectious etiology has been adequately ruled out. j. Prior bone marrow or stem cell transplantation.
  • Has any other medical, behavioral, or social condition that, in the opinion of the investigator, makes the participant ineligible to receive PM54, pembrolizumab, or undergo key trial procedures.
  • Exposure to the anticancer products/treatments below, without adequate washout period prior to first dose of study intervention. Note that hormonal therapy received for the adjuvant treatment of tumors at a low risk of relapse is allowed.
  • Products/treatments and washout periods:
  • Traditional Chinese or herbal medicine with the intent to treat cancer or with known effects on drug metabolism: 28 days.
  • Live, attenuated vaccines: 30 days.
  • Chemotherapy: 21 days.
  • Antibodies and antidrug conjugates: 28 days.
  • Targeted agents and small molecules: 2 weeks or 5 half-lives, whichever is longer.
  • Major surgery: 4 weeks. Note: Surgeries typically performed in an outpatient setting are not considered major, even if light sedation or an inpatient stay for oversight was needed.
  • Whole-brain radiation therapy, stereotactic therapy, palliative radiation for symptom control and minor impact on bone marrow: 2 weeks.
  • Other radiation therapy: 4 weeks.
  • Any medication associated with increased risk of torsade de pointes, except if considered indicated by the investigator, ideally for short duration, under medical monitoring and if no other risk factors for torsade de pointes are present such as prolonged QTc or significant electrolyte abnormalities.: 5 half-lives.
  • Strong or moderate inhibitors or inducers of cytochrome (CYP) 3A4: 2 weeks.
  • Corticosteroids: must be <= 10 mg/day of prednisone equivalent within 3 days of start of study intervention. The investigator is encouraged to review indication for ongoing use of corticosteroids and consider de-escalation or interruption if appropriate.
  • Active HIV infection. Inclusion is allowed if:
  • Undergoing adequate anti-viral treatment and regular clinical oversight with good compliance.
  • Undetectable human immunodeficiency virus (HIV) viral load.
  • CD4+ lymphocyte count over 350 per millimeter cube.
  • No evidence or suspicion of opportunistic infection. Note: The investigator should obtain and provide the sponsor with written documentation of the above, assessed by a medical doctor experienced in the management of individuals with HIV.
  • Individuals with detectable hepatitis C virus (HCV) ribonucleic acid (RNA), which should be tested in case of positive anti-HCV antibody test.
  • Positive serology test of hepatitis B surface antigen (HBsAg) with hepatitis B virus (HBV) DNA >= 1000 International Units per milliliter (IU/mL). Hepatitis B virus (HBV) DNA test is mandatory in case of HBsAg+. Individuals with detectable HBV DNA <1000 IU/mL or suspected occult HBV infection must undergo prophylaxis of HBV reactivation in order to be eligible.
  • Individuals with a short-term risk of anatomic complications from involvement of critical structures such as major vessels, large airways, and vertebral spine.
  • Women who are pregnant or breastfeeding and fertile participants (men and women) who are not using a highly effective method of contraception (see inclusion criterion No. 13).

Trial locations and contacts

11 sites in 2 countries. Contact the study team or a site near you to ask about taking part.

Cristian Fernandez, M.D. contact

0034 91 846 6077

cmfernandez@pharmamar.com

11 sites in 2 countries

United States6 sites, 6 recruiting

  • NEXT Virginia

    Fairfax, Virginia, 22031

    Recruiting

  • START Dallas

    Fort Worth, Texas, 76104

    Recruiting

  • The University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

    Recruiting

  • NEXT Houston

    Houston, Texas, 77054

    Recruiting

  • NEXT Dallas

    Irving, Texas, 75039

    Recruiting

  • START New York

    New York, New York, 11042

    Recruiting

Other trials in United States

Spain5 sites, 5 recruiting

  • Institut Català d'Oncologia (ICO) - Hospital Durans i Reynals.

    Barcelona

    Recruiting

  • Clinica Universidad de Navarra (CUN)

    Madrid

    Recruiting

  • Hospital General Universitario Gregorio Marañón

    Madrid

    Recruiting

  • START Madrid - Hospital Universitario Fundacion Jimenez D

    Madrid

    Recruiting

  • Clinica Universidad de Navarra (CUN)

    Pamplona

    Recruiting

Other trials in Spain

About this study

Official title: A Multicenter, Open-label, Phase 1/2 Safety Run-in and Expansion Study of PM54 in Combination With Immunotherapy Evaluating Safety and Efficacy in Adult Participants Who Were Previously Treated for Advanced Malignancies

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.

Being tested
Pembrolizumab, PM54

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Intravenous infusion.

  • PM54Drug

    Intravenous infusion.

Study groups in NCT07644039
Study groupRoleWhat they receive
Part 1 (safety Run-in): PM54 + PembrolizumabExperimentalParticipants 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.
Receives: Drug: Pembrolizumab; Drug: PM54
Part 2 (Dose Expansion): PM54 + PembrolizumabExperimentalParticipants will receive recommended dose of PM54 in combination with pembrolizumab as observed in Part 1 of the study.
Receives: Drug: Pembrolizumab; Drug: PM54

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    Measured: 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)

    Measured: 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).

    Measured: up to 12 weeks

  4. 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.

    Measured: Baseline up to 3 years

Secondary outcomes (9)

  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.

    Measured: Baseline up to 3 years

  2. 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).

    Measured: up to 12 weeks

  3. 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.

    Measured: Baseline up to 3 years

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

    Measured: Baseline up to 3 years

  5. Parts 1 and 2: Duration of Response (DoR)

    Measured: Baseline up to 3 years

  6. Parts 1 and 2: Time to Treatment Failure

    Measured: Baseline up to 3 years

  7. Parts 1 and 2: Overall Survival (OS)

    Measured: Baseline up to 3 years

  8. Parts 1 and 2: Percentage of Participants who Achieve a Minor Response

    Percentage of participants who achieve a minor response, defined as stable disease (per RECIST v1.1) with a reduction in sum of diameters of target lesions of 10% or greater, confirmed on a subsequent scan.

    Measured: Baseline up to 3 years

  9. Parts 1 and 2: Plasma Concentration of PM54 and Pembrolizumab

    Measured: Part 1- Cycle 1, Days 1 to 3: Pre-dose and at 1, 3, 6, 24 and 48 hours post-dose; Part 2- Cycle 1, Days 1 to 3: Pre-dose and at 1 and 48 hours post-dose (each cycle is 21 days)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Jun 2026
  2. Study start21 May 2026
  3. Primary completion2 Apr 2029 (estimated)
  4. Study completion2 Apr 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
119 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07644039
Sponsor's protocol ID
PM54-A-003-25
Other IDs
2025-523774-16, 2025
Status last verified
Oct 2026
First submitted
8 Jun 2026
Last updated
13 Oct 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 29753121

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Pembrolizumab and PM54 in people with Advanced Malignancies, run by PharmaMar at 11 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 11 sites in United States, Spain. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Cristian Fernandez, M.D. (0034 91 846 6077, cmfernandez@pharmamar.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07644039, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.

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