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

Advanced Tumor Clinical Trial

Official title:

A Phase I Study to Evaluate the Tolerability, Safety, Pharmacokinetic Characteristics and Preliminary Efficacy of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05607563
• Other study ID #: PM1009-A001M-ST-R
• Status: Recruiting
• Phase: Phase 1
• Start date: November 21, 2022
• Est. completion date: December 2023

Study information

• Verified date: November 2022
• Source: Biotheus Inc.
• Contact: Xuelian Xing
• Phone: +86 021 32120207
• Email: xing.xl[@]biotheus.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 54
• Est. completion date: December 2023
• Est. primary completion date: November 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Tumor

Intervention

Drug:
• PM1009 injection
Participants receive PM1009 intravenously, every 2 weeks

Locations

Country	Name	City	State
China	Shanghai Orient Hospital	Shanghai

Sponsors (1)

Lead Sponsor	Collaborator
Biotheus Inc.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	T-lymphocyte phenotypes	T-lymphocyte phenotypes in peripheral blood	Up to six cycles (each cycle is 2 weeks)
Primary	Dose Limited Toxicity(DLT)	Occurrence of DLT after receiving PM1009 injection	up to 21 days
Secondary	Recommended Phase II Dose (RP2D)	To determine the RP2D of PM1009 injection	Up to 30 days after last treatment
Secondary	Maximum observed concentration (Cmax)	To evaluate the Cmax of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Time to Cmax (Tmax)	To evaluate the Tmax of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Minimum observed concentration (Cmin)	To evaluate the Cmin of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Trough concentrations (Ctrough)	To evaluate the Ctrough of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Area under the concentration-time curve (AUC0-last)	To evaluate the AUC0-last of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	AUC to the end of the dosing period(AUC0-tau)	To evaluate the AUC0-tau of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Apparent terminal elimination half-life (t1/2)	To evaluate the t1/2 of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Accumulation ratio calculated based on Cmax (Rac_Cmax)	To evaluate the Rac_Cmax of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Accumulation ratio calculated based on AUC (Rac_AUC)	To evaluate the Rac_AUC of PM1009 monotherapy	Up to 30 days after last treatment
Secondary	Objective response rate (ORR)	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	Up to 24 months
Secondary	Disease control rate (DCR)	Defined as the percentage of patients who have achieved CR, PR, Non-CR/Non-PD, or SD in the study.	Up to 24 months
Secondary	Progression-free survival (PFS)	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.	Up to 24 months
Secondary	Overall survival (OS)	Defined as the time from the date of first dose of study drug to the date of documented death due to any cause.	Up to 24 months
Secondary	Anti-drug antibody (ADA)	To evaluate the incidence of ADA to PM1009 injection	Up to 30 days after last treatment
Secondary	Adverse Events(AE)and Serious Adverse Events(SAE)	The incidence and severity of treatment-emergent adverse events (TEAEs) and treatment related adverse events (TRAEs) graded according to NCI-CTCAE v5.0	Up to 30 days after last treatment