2025-523774-16-00
Recruiting
Phase 2
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
ConditionsAdvanced malignancies
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Pharma Mar S.A.
- Enrollment
- 36
- Locations
- 5
- Primary Endpoint
- Parts 1 and 2 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)
Overview
Brief Summary
Parts 1 and 2 To evaluate the safety and tolerability of PM54 in combination with pembrolizumab
Specific to Part 1 Only To determine the RD of PM54 in combination with pembrolizumab
Eligibility Criteria
- Ages
- 18 years to 65+ years (18-64 Years, 65+ Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Have read, understood, and signed the ICF before the start of any study-specific procedures.
- •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.
- •ECOG PS of 0 or 1 at Screening.
- •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.
- •Individuals with CNS metastases are eligible, as long as all of the following are met: a. Asymptomatic or minimally symptomatic and stable, with no worsening symptoms in the 4 weeks prior to start of trial treatment. b. Does not require systemic corticosteroids in excess of an equivalent prednisone dose of 5 mg/day. c. 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. d. 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 in the protocol.
- •Recovered from the effects of any prior surgery or radiation.
- •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 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.
- •Adults (≥18 years or legal consenting age, per local regulations), and able to provide free and informed consent for study participation.
Exclusion Criteria
- •Prior treatment with PM54 or any other ecteinascidin agent, including ecubectedin, trabectedin, and lurbinectedin.
- •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.
- •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). Valid methods to determine childbearing potential, adequate contraception, and requirements for WOCBP partners are described in the protocol.
- •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: a. History of myocardial, CNS, or other arterial infarction within 6 months before the start of study intervention. b. Heart failure Class II or higher according to the New York Heart Association or LVEF <45% per echocardiogram or MUGA. c. Symptomatic arrhythmia or other significant ECG abnormalities that in the opinion of the investigator pose an increased risk of complications. d. QTc interval >470 ms (females) or >450 ms (males) on the screening ECG or history of a long QT syndrome. Respiratory e. History of ILD or pneumonitis that have required steroids or other forms of immunosuppression, or any ongoing or suspicion of ILD. f. Severe 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. 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 h. 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 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. 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 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.
Outcomes
Primary Outcomes
Parts 1 and 2 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)
Parts 1 and 2 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)
Specific to Part 1 Only - DLTs during the DLT assessment period
Specific to Part 1 Only - DLTs during the DLT assessment period
Secondary Outcomes
- Duration of response
- Confirmed ORR per RECIST v1.1 (or mRECIST v1.1, where applicable) during the study
- CBR in the first 12 weeks
- 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
- Progression-free survival (PFS)
- Time to treatment failure
- Overall survival
- Plasma concentration of PM54 and pembrolizumab throughout the study
Investigators
Clinical Development Oncology Unit
Scientific
Pharma Mar S.A.
Study Sites (5)
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