Study to Assess the Safety, Tolerability, and Blood Concentration of PMC-309
ConditionAdvanced or Metastatic Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorPharmAbcine
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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.
Has received at least 2 doses of an approved anti-PD-1/L1 mAb.
Disqualifiers
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.
Trial design
Design model
Parallel
Treatments tested in this trial
PMC-309 monotherapy
DrugPMC-309 will be administered intravenously.
PMC-309 Dose Escalation in Combination with Pembrolizumab(KEYTRUDA®)
DrugBoth 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.
PMC-309 Dose Expansion
DrugPhase 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®)
Treatment groups
67 Participants
are divided into 3 treatment groupsGroup A: Phase 1 a: Part A: PMC-309 Monotherapy Dose EscalationExperimental treatment 1 intervention
Group B: Phase 1a: Part B: PMC-309 Dose Escalation in Combination with PembrolizumabExperimental treatment 1 intervention
Group C: Phase 1b: Dose ExpansionExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)2
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.
Time frame
Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)3
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.
Time frame
Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)4
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
Time frame
Phase 1a and 1b- Upto 35 Cycles (each cycle is 21 days)Secondary outcomes
1
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)
RECIST consisting of overall response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) will be graded following CT/MRI of chest, abdomen and pelvis.
Time frame
Upto 35 Cycles (each cycle is 21 days)2
The plasma pharmacokinetic endpoints of the study is assessed by peak serum concentration (Cmax)
Time frame
Upto 35 Cycles (each cycle is 21 Days)3
The plasma pharmacokinetic endpoints of the study is assessed by time to peak plasma concentration (Tmax)
Time frame
Upto 35 Cycles (each cycle is 21 Days)4
PK parameter assessed by serum concentration at specified timepoints for area under curve (AUC)
Time frame
Upto 35 Cycles (each cycle is 21 Days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
PharmAbcine
Lead sponsor
Novotech (Australia) Pty Limited
Collaborator
Merck Sharp & Dohme LLC
Collaborator
Source ClinicalTrials.gov