A Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumors
Overview
- Phase
- Phase 1
- Intervention
- PM1009 injection
- Conditions
- Advanced Tumor
- Sponsor
- Biotheus Inc.
- Enrollment
- 54
- Locations
- 1
- Primary Endpoint
- Dose Limited Toxicity（DLT）
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The study is being conducted to evaluate safety, tolerability, pharmacokinetics and preliminary efficacy of PM1009 for patients with advanced tumors, also to explore the recommended Phase Ⅱ Dose（RP2D） of PM1009.
PM1009 is a new novel fully human anti-TIGIT x PVRIG bispecific antibody, containing a wildtype IgG1 Fc and has high monovalent affinity to each target, it can binds to both TIGIT and PVRIG overexpressing target cells and binds to TIGIT and PVRIG simultaneously.
Detailed Description
This is a single-arm, open-label, Phase I study contains dose escalation stage and dose expansion stage. The dose escalation stage will be following the accelerated titration design and the classic 3+3 design, with a planned enrollment of 10 to 24 patients with advanced tumors. The dose expansion stage will be used safe and tolerable doses, with a planned enrollment of 30 patients with advanced tumors.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patients participate in the study voluntarily and sign informed consent；
- •Male or female, aged 18 to 75 years (including boundary value);
- •Subjects with advanced tumor confirmed by histology or cytology fail to receive standard treatment, or there is no standard treatment scheme, or standard treatment is not applicable at this stage;
- •Having adequate organ function；
- •ECOG score is 0-1；
- •Expected survival ≥ 12 weeks；
- •There is at least one assessable tumor focus.
Exclusion Criteria
- •History of severe allergic;
- •Those who have received anti-TIGIT or anti-PVRIG therapy in the past;
- •Patients who have grade ≥3 immune-mediated adverse event that associated with a prior immunotherapy;
- •Adverse reactions to previous antitumor therapy have not recovered to NCI-CTCAE V5.0 rating ≤ 1;
- •Current definite interstitial lung disease or non-infectious pneumonitis, except for local radiotherapy;
- •Patients ever received the following treatments or drugs prior to the study treatment:
- •Major organ surgery within 28 days prior to initiation of trial treatment;
- •Received live attenuated vaccine within 28 days prior to the study treatment;
- •Received antitumor therapy within 4 weeks prior to the study treatment;
- •Received systemic glucocorticoid within 14 days prior to the study treatment;
Arms & Interventions
PM1009 120 mg monotherapy
PM1009 120 mg
Intervention: PM1009 injection
PM1009 300 mg monotherapy
PM1009 300 mg
Intervention: PM1009 injection
PM1009 600 mg monotherapy
PM1009 600 mg
Intervention: PM1009 injection
PM1009 1200 mg monotherapy
PM1009 1200 mg
Intervention: PM1009 injection
Outcomes
Primary Outcomes
Dose Limited Toxicity（DLT）
Time Frame: up to 21 days
Occurrence of DLT after receiving PM1009 injection
Secondary Outcomes
- Recommended Phase II Dose (RP2D)(Up to 30 days after last treatment)
- Maximum observed concentration (Cmax)(Up to 30 days after last treatment)
- Minimum observed concentration (Cmin)(Up to 30 days after last treatment)
- Area under the concentration-time curve (AUC0-last)(Up to 30 days after last treatment)
- AUC to the end of the dosing period(AUC0-tau)(Up to 30 days after last treatment)
- Accumulation ratio calculated based on Cmax (Rac_Cmax)(Up to 30 days after last treatment)
- Disease control rate (DCR)(Up to 24 months)
- Trough concentrations (Ctrough)(Up to 30 days after last treatment)
- Accumulation ratio calculated based on AUC (Rac_AUC)(Up to 30 days after last treatment)
- Anti-drug antibody (ADA)(Up to 30 days after last treatment)
- Time to Cmax (Tmax)(Up to 30 days after last treatment)
- Objective response rate (ORR)(Up to 24 months)
- Overall survival (OS)(Up to 24 months)
- Apparent terminal elimination half-life (t1/2)(Up to 30 days after last treatment)
- Progression-free survival (PFS)(Up to 24 months)
- Adverse Events（AE）and Serious Adverse Events（SAE）(Up to 30 days after last treatment)