Clinical trial NCT05607563: A Study of PM1009 (Anti-TIGIT/PVRIG) in Patients With Advanced Tumours
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
Conditions: Advanced Tumor
Keywords: PM1009
TIGIT
PVRIG
Lead sponsor: Biotheus Inc.
Sponsor class: INDUSTRY
First posted: 2022-11-07
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Patients sequentially receive PM1009 120 mg, 300 mg, 600 mg, 1200 mg, intravenously, Q2W
Primary purpose: TREATMENT

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.

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:

  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.

Primary outcomes:
measure: Dose Limited Toxicity（DLT）
timeFrame: up to 21 days
Secondary outcomes:
measure: Recommended Phase II Dose (RP2D)
timeFrame: Up to 30 days after last treatment
measure: Maximum observed concentration (Cmax)
timeFrame: Up to 30 days after last treatment
measure: Time to Cmax (Tmax)
timeFrame: Up to 30 days after last treatment
measure: Minimum observed concentration (Cmin)
timeFrame: Up to 30 days after last treatment
measure: Trough concentrations (Ctrough)
timeFrame: Up to 30 days after last treatment
measure: Area under the concentration-time curve (AUC0-last)
timeFrame: Up to 30 days after last treatment
measure: AUC to the end of the dosing period(AUC0-tau)
timeFrame: Up to 30 days after last treatment
measure: Apparent terminal elimination half-life (t1/2)
timeFrame: Up to 30 days after last treatment
measure: Accumulation ratio calculated based on Cmax (Rac_Cmax)
timeFrame: Up to 30 days after last treatment
measure: Accumulation ratio calculated based on AUC (Rac_AUC)
timeFrame: Up to 30 days after last treatment
measure: Objective response rate (ORR)
timeFrame: Up to 24 months
measure: Disease control rate (DCR)
timeFrame: Up to 24 months
measure: Progression-free survival (PFS)
timeFrame: Up to 24 months
measure: Overall survival (OS)
timeFrame: Up to 24 months
measure: Anti-drug antibody (ADA)
timeFrame: Up to 30 days after last treatment
measure: Adverse Events（AE）and Serious Adverse Events（SAE）
timeFrame: Up to 30 days after last treatment
Other outcomes:
measure: T-lymphocyte phenotypes
timeFrame: Up to six cycles (each cycle is 2 weeks)
Locations:
city: Shanghai
country: China
facility: Shanghai Orient Hospital
Study officials:
affiliation: Shanghai Orient Hospital
name: Ye Guo
role: PRINCIPAL_INVESTIGATOR
References: