A Study of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumours

Phase 1

Recruiting

• Conditions: Advanced Tumor
• Interventions: Drug: PM1009 injection

• Registration Number: NCT05607563
• Lead Sponsor: Biotheus Inc.

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.

Study Timeline

• Study First Submitted: 2022-10-19
• Status Verified: 2022-11
• Study First Submitted QC: 2022-11-04
• Study First Posted: 2022-11-07
• Study Start: 2022-11-21
• Last Update Submitted: 2023-02-07
• Last Update Posted: 2023-02-08
• Primary Completion: 2023-11
• Study Completion: 2023-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 54

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:

  1. Major organ surgery within 28 days prior to initiation of trial treatment;
  2. Received live attenuated vaccine within 28 days prior to the study treatment;
  3. Received antitumor therapy within 4 weeks prior to the study treatment;
  4. Received systemic glucocorticoid within 14 days prior to the study treatment;

• Active infection was present within 14 days before starting study treatment;

• Those with known uncontrolled parenchymal or leptomeningeal metastases;

• Patients with active autoimmune disease or a history of autoimmune disease with potential for relapse;

• Patients with other active malignancies within 5 years prior to initiation of study treatment, except for locally treatable and cured malignancies;

• History of severe cardiovascular and cerebrovascular diseases;

• Patients with uncontrolled tumor-related pain;

• Current presence of uncontrolled pleural, pericardial, and peritoneal effusions;

• History of allogeneic hematopoietic stem cell transplantation or allogeneic organ transplantation;

• History of alcohol, psychotropic substance or drug abuse;

• History of psychiatric disorders or poor compliance;

• History of immunodeficiency, including a positive HIV antibody test;

• Patients with active syphilis infection;

• Patients with active hepatitis B or C;

• Pregnant or lactating women;

• Other conditions considered unsuitable for this study by investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
PM1009 300 mg monotherapy	PM1009 injection	PM1009 300 mg
PM1009 120 mg monotherapy	PM1009 injection	PM1009 120 mg
PM1009 1200 mg monotherapy	PM1009 injection	PM1009 1200 mg
PM1009 600 mg monotherapy	PM1009 injection	PM1009 600 mg

Primary Outcome Measures

Name	Time	Method
Dose Limited Toxicity（DLT）	up to 21 days	Occurrence of DLT after receiving PM1009 injection

Secondary Outcome Measures

Name	Time	Method
Recommended Phase II Dose (RP2D)	Up to 30 days after last treatment	To determine the RP2D of PM1009 injection
Maximum observed concentration (Cmax)	Up to 30 days after last treatment	To evaluate the Cmax of PM1009 monotherapy
Minimum observed concentration (Cmin)	Up to 30 days after last treatment	To evaluate the Cmin of PM1009 monotherapy
Area under the concentration-time curve (AUC0-last)	Up to 30 days after last treatment	To evaluate the AUC0-last of PM1009 monotherapy
AUC to the end of the dosing period(AUC0-tau)	Up to 30 days after last treatment	To evaluate the AUC0-tau of PM1009 monotherapy
Accumulation ratio calculated based on Cmax (Rac_Cmax)	Up to 30 days after last treatment	To evaluate the Rac_Cmax of PM1009 monotherapy
Disease control rate (DCR)	Up to 24 months	Defined as the percentage of patients who have achieved CR, PR, Non-CR/Non-PD, or SD in the study.
Trough concentrations (Ctrough)	Up to 30 days after last treatment	To evaluate the Ctrough of PM1009 monotherapy
Accumulation ratio calculated based on AUC (Rac_AUC)	Up to 30 days after last treatment	To evaluate the Rac_AUC of PM1009 monotherapy
Anti-drug antibody (ADA)	Up to 30 days after last treatment	To evaluate the incidence of ADA to PM1009 injection
Time to Cmax (Tmax)	Up to 30 days after last treatment	To evaluate the Tmax of PM1009 monotherapy
Objective response rate (ORR)	Up to 24 months	Defined as the number of patients with best overall response of confirmed CR or PR per RECIST 1.1 divided by the patients with at least one tumour imaging evaluation
Overall survival (OS)	Up to 24 months	Defined as the time from the date of first dose of study drug to the date of documented death due to any cause.
Apparent terminal elimination half-life (t1/2)	Up to 30 days after last treatment	To evaluate the t1/2 of PM1009 monotherapy
Progression-free survival (PFS)	Up to 24 months	Defined as the time from the date of first dose of study drug to the first observation of documented disease progression per RECIST 1.1 as determined by the Investigators or death due to any cause, whichever occurs first.
Adverse Events（AE）and Serious Adverse Events（SAE）	Up to 30 days after last treatment	The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) graded according to NCI-CTCAE v5.0

Trial Locations

Locations (1)

Shanghai Orient Hospital; 🇨🇳 Shanghai, China