Study to Assess the Safety, Tolerability, and Blood Concentration of PMC-309

NCT05957081 | Recruiting Phase 1 DMC

• 3 other identifiers: MarkV-01KEYNOTE-E80MK-3475-E80
• Study Type: interventional
• Target: 67
• Locations: 1 country
• Sites: 4

Brief Summary

This is a Phase 1a/1b, first-in-human (FIH), open label study to evaluate the safety, tolerability, and pharmacokinetics (PK) of PMC-309, a mAb against the human VISTA ligand, in participants with advanced or metastatic solid tumors administered as a monotherapy and in combination with pembrolizumab.

Conditions

Advanced or Metastatic Solid Tumors

Keywords

PMC-309 and Anti-VISTA

Outcome Measures

Primary Outcomes (9)

• Number of participants with abnormal vital signs in response ot treatment with PMC- 309

  Vital signs will be assessed by changes in systolic/diastolic blood pressure, respiratory rate, body temperature and heart rate.

  Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)

• Number of participants with abnomal clinically significant results with physical examination in response to the treatment with PMC-309

  A complete physical examinations of general appearance, head, ears, eyes, nose, throat, dentition, thyroid, chest (heart, lungs), abdomen, skin, neurological, extremities, back, neck, musculoskeletal, and lymph nodes.

  Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)

• Number of participants with abnormal clinically significant 12-lead electrocardiogram (ECG) parameters in response to treatment with PMC-309

  The following ECG parameters will be recorded: heart rate, RR interval, HR interval, QTc interval, and QRS interval.

  Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)

• Number of participants with abnormal clinically significant laboratory results in response to treatment with PMC-309

  Laboratory results will include biochemistry, Thyroid function test, hematology, coagulation and urinalysis

  Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)

• Number of participants with adverse events receiving treatment with PMC-309

  Adverse events includes \[treatment-emergent AE, serious AEs, treatment-emergent AEs of special interest\] which will be coded using most current version of MedDRA.

  Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)

• Number of participants with abnormal changes in Eastern Cooperative Oncology Group (ECOG) performance status.

  Phase 1a and 1b- Screening

• Number of participants with abnormal changes in Eastern Cooperative Oncology Group (ECOG) performance status.

  Day1 of every cycle (each cycle is 21 days)

• To determine the maximum tolerated dose (MTD) of PMC-309 monotherapy (Part A) and establish the preliminary RP2D of PMC-309.

  MTD of PMC-309 will be calculated by incidence of DLT at 21 days from the first dosing of PMC 309.

  Upto 21 days

• To determine the MTD and establish the preliminary RP2D of PMC-309 when administered in combination with pembrolizumab at 200 mg (Part B).

  MTD of PMC-309 by incidence of DLT at 21 days from the first dosing of PMC-309 in combination with pembrolizumab.

  Upto 21 Days

Secondary Outcomes (6)

• To assess the clinical efficacy of PMC-309 in the treatment of advanced or metastatic solid tumors by Response Evaluation Criteria in Solid Tumors (RECIST v1.1)

  Upto 35 Cycles (each cycle is 21 days)

• The plasma pharmacokinetic endpoints of the study is assessed by peak serum concentration (Cmax)

  Upto 35 Cycles (each cycle is 21 Days)

• The plasma pharmacokinetic endpoints of the study is assessed by time to peak plasma concentration (Tmax)

  Upto 35 Cycles (each cycle is 21 Days)

• PK parameter assessed by serum concentration at specified timepoints for area under curve (AUC)

  Upto 35 Cycles (each cycle is 21 Days)

• To assess the clinical efficacy of PMC-309 at the RP2D as a monotherapy and in combination with pembrolizumab

  Upto 35 Cycles (each cycle is 21 Days)

Study Arms (3)

Phase 1 a: Part A: PMC-309 Monotherapy Dose Escalation

EXPERIMENTAL

Phase 1a will enroll participants with advanced or metastatic solid tumors to assess safety, tolerability, PK and clinical efficacy in response to treatment with PMC-309 as a monotherapy Dosage form and Route of administration: The duration of a treatment cycle is 3 weeks/21 days. Participants will be administered a weekly dose of PMC-309 per cycle as follows: * Cycle Week 1/Day 1 * Cycle Week 2/Day 8 ± 2 days * Cycle Week 3/Day 15 ± 2 days PMC-309 will be administered intravenously over 1 hour (± 0.5 hours), after which participants will be observed for a period of 1.5 hours post administration.

Drug: PMC-309 monotherapy

Phase 1a: Part B: PMC-309 Dose Escalation in Combination with Pembrolizumab

EXPERIMENTAL

Part B will establish the MTD/preliminary RP2D of PMC-309 when administered in combination with 200 mg pembrolizumab. Part B will be conducted after completion of Part A (PMC-309 monotherapy dose escalation) and before the commencement of Phase 1b. Dosage form and Route of administration: The duration of a treatment cycle is 3 weeks/21 days. Participants will be administered a weekly dose of PMC-309 plus one dose of pembrolizumab at 200 mg per cycle as follows: * Cycle Week 1/Day 1: pembrolizumab (administered first), followed by administration of PMC-309. * Cycle Week 2/Day 8 ± 2 days: PMC-309 only * Cycle Week 3/Day 15 ± 2 days: PMC-309 only. Both PMC-309 and pembrolizumab will be administered intravenously.

Drug: PMC-309 Dose Escalation in Combination with Pembrolizumab(KEYTRUDA®)

Phase 1b: Dose Expansion

EXPERIMENTAL

Phase 1b will enroll participants after completion of DLT assessments for Phase 1a. Phase 1b will enroll participants with advanced or metastatic tumor types into 1 of 2 cohorts to assess response of monotherapy of PMC-309 and response of PMC-309 in combination with pembrolizumab. * Cohort A: PMC-309 monotherapy therapy \- PMC-309 dosing will be at the preliminary RP2D, as identified in Phase 1a: Part A * Cohort B: PMC-309 plus pembrolizumab combination therapy - PMC-309 dosing will be as identified in Phase 1a: Part B in combination with 200 mg pembrolizumab Participants will be randomly assigned to Cohort A or Cohort B until 20 participants are enrolled in each cohort.

Drug: PMC-309 Dose Expansion

Interventions

PMC-309 monotherapy DRUG

PMC-309 will be administered intravenously.

Also known as: Monotherapy

Phase 1 a: Part A: PMC-309 Monotherapy Dose Escalation

PMC-309 Dose Escalation in Combination with Pembrolizumab(KEYTRUDA®) DRUG

Both PMC-309 and pembrolizumab will be administered intravenously. At the time of the combination therapy (Week 1/Day 1 of each cycle), participants will be dosed with pembrolizumab(KEYTRUDA®) first, administered over 0.5 hours (± 10 minutes). Following an interval of 1 hour (± 15 minutes), participants will be dosed with PMC-309 administered over 1 hour (± 0.5 hours), after which participants will be observed for a period of 1.5 hours post administration.

Also known as: Combination Therapy

Phase 1a: Part B: PMC-309 Dose Escalation in Combination with Pembrolizumab

PMC-309 Dose Expansion DRUG

Phase 1b will enroll participants with advanced or metastatic tumor types into 1 of 2 cohorts: * Cohort A: PMC-309 monotherapy therapy \- PMC-309 dosing will be at the preliminary RP2D, as identified in Phase 1a: Part A * Cohort B: PMC-309 plus pembrolizumab(KEYTRUDA®) combination therapy - PMC-309 dosing will be as identified in Phase 1a: Part B in combination with 200 mg pembrolizumab(KEYTRUDA®)

Also known as: Mono and Combination therapy

Phase 1b: Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The participant voluntarily signs an informed consent form (ICF) indicating they understand the purpose and procedures required for the study and are willing to participate in the study.
• Are at least 18 years of age.
• Are diagnosed with advanced or metastatic solid tumors (non-lymphoma) by histology or pathology that is metastatic or unresectable and considered relapsed and/or refractory to prior therapy.
• Definition of anti-PD-1/L1 refractory participant:
• Participants must have progressed on treatment with an anti-PD1/L1 mAb administered either as monotherapy, or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria:
• Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
• Has demonstrated disease progression (PD) after PD-1/L1 as defined by RECIST v1.1. The initial evidence of PD is to be confirmed by a second assessment no less than 4 weeks from the date of the first documented PD, in the absence of rapid clinical progression.
• PD has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb.
• i. PD is determined according to iRECIST v1.1. ii. This determination is made by the PI (or designee). Once PD is confirmed, the initial date of PD documentation will be considered the date of disease progression
• Have measurable disease per RECIST v1.1 documented by computerized tomography scan (CT scan) and/or magnetic resonance imaging (MRI), measurable at Baseline. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Have an ECOG performance status of 0 or 1.
• Can satisfy the following criteria in hematologic, renal, and hepatic function tests performed within 7 days prior to screening:
• Hematologic tests:
• ANC more than and equal to 1.5 × 109 per L.
• Platelets more than and equal to 100 × 109 per L.

You may not qualify if:

• Has received treatment with a VISTA targeting agent.
• Has a history of positive testing for hepatitis B surface antigen (HBsAg) or hepatitis C antibody (anti-hepatitis C virus) or other clinically active liver disease, or positive testing at Screening for HBsAg or anti- hepatitis C virus.
• HIV-infected participants with a history of Kaposi sarcoma and/or Multicentric Castleman Disease.
• Has a medical condition which, in the opinion of the PI (or designee), places the participant at an unacceptably high risk for toxicity.
• Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
• Is currently participating in or has participated in a study of an investigational agent or have received anticancer immunotherapy within 4 weeks prior to the first dose of IP.
• Has an active autoimmune disease with a history of flares requiring immunosuppressant medications within the past 6 months or that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed.
• History of known or suspected seizure disorder.
• Has oxygen-dependent chronic disease.
• Serious Grade 4 venous thromboembolic event including pulmonary embolism.
• Participant is receiving therapeutic anticoagulants.
• Has had an allogeneic tissue/solid organ transplant.
• Major surgery (eg, requiring general anesthesia) within 4 weeks before the planned first dose of the IP, or not fully recovered from prior surgery, or has surgery planned during the time the participant is expected to participate in the study or within 4 weeks after the last dose of IP.
• Participant is pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 120 days after the last dose of IP; WOCBP must have a negative pregnancy status confirmed by urine pregnancy test at Screening and within 72 hours of first dose of the IP. (If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.)
• Participant is a man who plans to father a child while enrolled in this study or within 3 months after the last dose of the IP.

Sponsors & Collaborators

• PharmAbcine: lead
• Novotech (Australia) Pty Limited: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

Australian Hospital Care (Pindara) PTY LTD. Trading as Pindara Private Hospital

Benowa, Queensland, 4217, Australia

RECRUITING

Ballarat Regional Integrated Cancer Centre (Grampians Health)

Ballarat, Victoria, 3350, Australia

RECRUITING

Cabrini Health Limited

Malvern, Victoria, 3144, Australia

RECRUITING

Alfred Health

Melbourne, Victoria, 3004, Australia

RECRUITING

MeSH Terms

Interventions

Combined Modality Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Study Officials

• Andrea Tazbirkova, Dr

  Pindara Private Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hyojin Koh, Dr

CONTACT

070-4213-2925; hyojin.koh@pharmabcine.com

Study Design

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

Study Record Dates

• First Submitted: May 26, 2023
• First Posted: July 24, 2023
• Study Start: January 3, 2024
• Primary Completion (Estimated): October 30, 2029
• Study Completion (Estimated): April 30, 2030
• Last Updated: December 30, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

AU (4)