PM54 for Advanced malignancies

Inclusion criteria

• {"criterion_text":"- Have read, understood, and signed the ICF before the start of any study-specific procedures."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- ECOG PS of 0 or 1 at Screening."}
• {"criterion_text":"- No ongoing toxicities from prior anticancer treatment of Grade >1 (per NCI CTCAE v6.0), 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 hormonal replacement therapy as applicable."}
• {"criterion_text":"- Individuals with CNS metastases are eligible, as long as all of the following are met: a.\tAsymptomatic or minimally symptomatic and stable, with no worsening symptoms in the 4 weeks prior to start of trial treatment. b.\tDoes not require systemic corticosteroids in excess of an equivalent prednisone dose of 5 mg/day. c.\tHas 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. d.\tHave 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."}
• {"criterion_text":"- Adequate laboratory parameters, as specified in the protocol."}
• {"criterion_text":"- Recovered from the effects of any prior surgery or radiation."}
• {"criterion_text":"- Is willing to undergo trial procedures as specified in the protocol, including provision of biologic samples, as well as any study restrictions."}
• {"criterion_text":"- Evidence of non-childbearing status for 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. Valid methods to determine the childbearing potential, adequate contraception, and requirements for WOCBP partners are described in the protocol. Fertile male participants with WOCBP partners should agree to use condoms during treatment and for 4 months following the last study intervention infusion."}
• {"criterion_text":"- Adults (≥18 years or legal consenting age, per local regulations), and able to provide free and informed consent for study participation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Have measurable disease according to RECIST v1.1 (or mRECIST v1.1 where applicable)."}

Exclusion criteria

• {"criterion_text":"- Prior treatment with PM54 or any other ecteinascidin agent, including ecubectedin, trabectedin, and lurbinectedin."}
• {"criterion_text":"- Positive serology test of HBsAg with HBV DNA ≥1000 IU/mL. 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."}
• {"criterion_text":"- Individuals with a short-term risk of anatomic complications from involvement of critical structures such as major vessels, large airways, and vertebral spine."}
• {"criterion_text":"- 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). Valid methods to determine childbearing potential, adequate contraception, and requirements for WOCBP partners are described in the protocol."}
• {"criterion_text":"- History of hypersensitivity to PM54, pembrolizumab, or any of the inactive ingredients."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Presence of carcinomatous meningitis."}
• {"criterion_text":"- Presence of any of these medical conditions. Cardiovascular: a.\tHistory of myocardial, CNS, or other arterial infarction within 6 months before the start of study intervention. b.\tHeart failure Class II or higher according to the New York Heart Association or LVEF <45% per echocardiogram or MUGA. c.\tSymptomatic arrhythmia or other significant ECG abnormalities that in the opinion of the investigator pose an increased risk of complications. d.\tQTc interval >470 ms (females) or >450 ms (males) on the screening ECG or history of a long QT syndrome. Respiratory e.\tHistory of ILD or pneumonitis that have required steroids or other forms of immunosuppression, or any ongoing or suspicion of ILD. f.\tSevere underlying lung disorders, 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. g.\tNew 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 h.\tHistory 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 end organ involvement or (c) has required corticosteroids >10 mg/day of prednisone equivalent or other systemic immunosuppressants in the previous 1 year to control a disease flare. i.\tUncontrolled 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.\tPrior bone marrow or stem cell transplantation."}
• {"criterion_text":"- 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."}
• {"criterion_text":"- Exposure to the anticancer products/treatments listed in the protocol, 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."}
• {"criterion_text":"- Active HIV infection. Inclusion is allowed if: a.\tUndergoing adequate anti-viral treatment and regular clinical oversight with good compliance. b.\tUndetectable HIV viral load. c.\tCD4+ lymphocyte count over 350/mm3. d.\tNo evidence or suspicion of opportunistic infection."}
• {"criterion_text":"- Individuals with detectable HCV RNA, which should be tested in case of positive anti-HCV antibody test."}

Primary endpoints

• {"endpoint_text":"- Parts 1 and 2\t Treatment-emergent adverse events (TEAEs), serious TEAEs, dose-limiting toxicities (DLTs), TEAEs leading to treatment discontinuation or dose modifications; these will be considered in the determination of the recommended dose (RD)","definition_or_measurement_approach":"Safety endpoints (TEAEs, serious TEAEs, DLTs, TEAEs leading to discontinuation or dose modifications) to be collected during treatment and considered in determination of the recommended dose (RD)."}
• {"endpoint_text":"- Specific to Part 1 Only - DLTs during the DLT assessment period","definition_or_measurement_approach":"Occurrence of dose-limiting toxicities (DLTs) assessed during the defined DLT assessment period (as specified in the protocol)."}

Secondary endpoints

• {"endpoint_text":"- Confirmed ORR per RECIST v1.1 (or mRECIST v1.1, where applicable) during the study","definition_or_measurement_approach":"Objective response rate assessed and confirmed according to RECIST v1.1 (or mRECIST v1.1 where applicable)."}
• {"endpoint_text":"- CBR in the first 12 weeks","definition_or_measurement_approach":"Clinical benefit rate measured in the first 12 weeks (definition per protocol)."}
• {"endpoint_text":"- Disease control rate, defined as the proportion of participants who achieve a best overall response of stable disease, PR, or CR as defined by RECIST v1.1 (or mRECIST v1.1, where applicable) during the study","definition_or_measurement_approach":"Disease control rate = proportion achieving best overall response of stable disease, partial response (PR), or complete response (CR) per RECIST v1.1 (or mRECIST v1.1)."}
• {"endpoint_text":"- Progression-free survival (PFS)","definition_or_measurement_approach":""}
• {"endpoint_text":"- Duration of response","definition_or_measurement_approach":""}
• {"endpoint_text":"- Time to treatment failure","definition_or_measurement_approach":""}
• {"endpoint_text":"- Overall survival","definition_or_measurement_approach":""}
• {"endpoint_text":"- Plasma concentration of PM54 and pembrolizumab throughout the study","definition_or_measurement_approach":"Pharmacokinetic sampling to assess plasma concentrations of PM54 and pembrolizumab during the study."}

Spain

Earliest CTIS Part Ii Submission Date

10-04-2026

Latest Decision Or Authorization Date

24-04-2026

Processing Time Days

14

Number Of Sites

5

Number Of Participants

36

Primary sponsor

Full Name

Pharma Mar S.A.

Organisation Type

Pharmaceutical company

Country Of Registered Address

Spain

Contract research organisations

Name

Syneos Health Inc.

Responsibilities

codes: 1,10,11,12,13,14,2,5,6,8

Name

Suvoda LLC

Responsibilities

code: 3

Name

Medidata Solutions Inc.

Responsibilities

codes: 6,7

Name

Acm Global Central Laboratory Limited

Responsibilities

code: 4

Third parties

• {"country":"United Kingdom","full_name":"Acm Global Central Laboratory Limited","duties_or_roles":"code: 4","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Tempus AI Inc.","duties_or_roles":"code: 4","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Spain","full_name":"Kymos S.L.","duties_or_roles":"code: 4","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"codes: 6,7","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Syneos Health Inc.","duties_or_roles":"codes: 1,10,11,12,13,14,2,5,6,8","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code: 3","organisation_type":"Non-Pharmaceutical company"}
• {"country":"France","full_name":"Median Technologies","duties_or_roles":"Central imaging","organisation_type":"Pharmaceutical company"}