All Drugs and Chemicals

Antibodies

Antibodies, Monoclonal

Immunoglobulins

1. JS006 as Monotherapy dose-escalation：5 proposed dose levels（18mg, 60mg, 180mg, 600mg, 1800mg).
2. JS006 as Monotherapy dose-extension：1 or 2 proposed dose levels, to be determined.

1. JS006 in combination with Toripalimab dose-escalation：2 or 3 proposed dose levels, to be determined.
2. JS006 in combination with Toripalimab dose-extension：1 or 2 proposed dose levels, to be determined.
3. JS006 in combination with Toripalimab indications expansion: 2 to 4 specific tumor types are selected for indication expansion after the combination dose-expansion is completed.

1. JS006 as Monotherapy dose-escalation: JS006, 18/ 60/ 180/ 600/ 1800mg, IV infusion, every 3 weeks (q3w).
2. JS006 as Monotherapy dose-extension: JS006, 1 or 2 specific dose, IV infusion, every 3 weeks (q3w).

JS006 as Monotherapy

1. JS006 in combination with Toripalimab dose-escalation: JS006, 2 or 3 specific dose, IV infusion, every 3 weeks (q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w).
2. JS006 in combination with Toripalimab dose-extension: JS006, 1 or 2 specific dose, IV infusion, every 3 weeks (q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w).
3. JS006 in combination with Toripalimab indications expansion: JS006, RP2D, IV infusion, every 3 weeks(q3w), combined with Toripalimab, 240mg, IV infusion, every 3 weeks (q3w).

JS006 in combination with Toripalimab

Bifeng Liu

Ruihua Xu, PHD,MD

This is an open-label, dose-escalation and dose-expansion phase I clinical study to evaluate the safety and tolerability of JS006 as Monotherapy and in combination with toripalimab in patients with advanced tumors who have failed standard therapies or who have no standard therapy. It is planned to enroll 69-176 patients into the study.

The Recombinant Humanized Anti-TIGIT Monoclonal Antibody (JS006) Monotherapy and in Combination With Toripalimab in Patients With Advanced Tumor

A Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Initial Efficacy of Recombinant Humanized Anti-TIGIT Monoclonal Antibody (JS006) Monotherapy and in Combination With Toripalimab in Patients With Advanced Tumors

The relationship between efficacy and potential biomarkers in tumor tissue: CD155 expression in tumor tissue.

The relationship between efficacy and potential biomarkers in tumor tissue: whole exome sequencing (WES) for tumor mutation burden (TMB) in tumor tissue.

The relationship between efficacy and potential biomarkers in tumor tissue: whole exome sequencing (WES) for tumor microsatellite instability (MSI) in tumor tissue.

Immune cell surface receptors testing in peripheral blood

Incidence and severity of dose limiting toxicity (DLT), adverse events (AEs), serious adverse events (SAEs), and immune-related adverse events (irAEs); abnormal changes with clinical significance in the laboratory and other tests

Maximum tolerated dose: Dose Limitted Toxictiy events occurred at a rate less than 1/3 of the maximum tolerated dose.

Phase II recommended dose: safety, pharmacokinetics, and preliminary efficacy data of dose escalation will be integrated. When the Maximum tolerated dose(MTD) is determined, the Maximum tolerated dose(MTD) is usually used as the Phase II recommended dose(RP2D), or the dose lower than the Maximum tolerated dose(MTD) is selected as the Phase II recommended dose(RP2D) based on the comprehensive data.

JS006 concentrations in individual subjects at different time points after dosing of JS006.

Immunogenicity: incidence of anti-drug antibodies (ADAs) and/or neutralizing antibodies (Nabs) of JS006 and toripalimab.

Peripheral blood immune cell subset and receptor occupancy of TIGIT

The percentage of cases with remission (PR + CR) after treatment was assessable.

The time from the first assessment of CR or PR to the first assessment of PD or death due to any cause.

The percentage of cases with remission (PR + CR) and stable lesions (SD) after treatment was assessable.

time from the start of treatment to progression of diease.

PFS is defined as time from the start of treatment to progression of disease or death.

Overall survival is defined as time from the start of treatment until death due to any reason.

Spots Global Cancer Trial Database for js006 in combination with toripalimab