NCT05868876

A Phase Ia/Ib Open Label，Clinical Study Evaluating the Safety, Tolerability and Preliminary Efficacy of AK127 in Combination With AK104 in Patients With Advanced Malignant Tumors

• Status: Recruiting
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 205 (estimated)
• Sponsor: Akeso · Industry
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

A Phase Ia/Ib open label，clinical study evaluating the safety, tolerability and preliminary efficacy of AK127 in combination with AK104 in patients with advanced malignant tumors

Detailed description

Immunocheckpoint inhibitors has greatly improved the efficacy of cancer treatment,such as in non-small cell lung cancer, melanoma, urothelial carcinoma and other tumor species, greatly improving patient survival. However, some patients still do not benefit from current immunotherapy (PD- (L) 1, or CTLA-4), suggesting that there are other mechanisms that limit the immune response within the tumor.As a result, the current immune checkpoint inhibitors (PD- (L) 1, CTLA-4) are not effective or even ineffective in some patients. AK104 is a humanized immunoglobulin G1 (IgG1) bispecific antibody (BsAb),AK104 binds both programmed cell death 1 (PD-1) and cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) and blocks the interaction of PD-1/ programmed cell death ligand 1 (PD-L1), PD-1/PD-L2, CTLA-4/B7.1 and CTLA-4/B7.2.In June 2022, Akeso bis-specific antibody Cardonilimab (AK104) was approved by the CDE for marketing in the treatment of patients with recurrent or metastatic cervical cancer who have failed previous platinum-containing chemotherapy. AK127 is a TIGIt-targeting IgG1 monoclonal antibody with complete Fc function. It can bind to human immune cells TIGIT with high affinity and competitively block the binding of TIGIT to its ligands CD155 and CD112.Elimination of Treg in tumor by NK cells and enhancement of anti-tumor activity of CD8+T cell , without causing regulatory T cell depletion, thus promoting anti-tumor immune response.AK127 is expected to be a more effective immune checkpoint inhibitor. The simultaneous blocking of PD1/PDL1, CTLA4 and TIGIT is expected to simultaneously relieve tumor immunosuppression at multiple immune checkpoints, enhance anti-tumor immune response, and provide more clinical solutions. AK104 is PD1 and CTLA4 bispecific antibody, and AK127 is TIGIT monoclonal antibody.Combined application may further enhance the antitumor effect.The objective of this study was to explore the safety, tolerability, pharmacokinetics, pharmacodynamics, and initial antitumor activity of AK104 combined with AK127 in advanced malignant tumors.

Conditions

• Advanced Malignant Tumors

Interventions

Type	Name	Description
DRUG	AK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion	AK127 is administered intravenously according to the frequency Q3W and different dosage of administration at different stages.AK104 is administered intravenously according to the frequency and dosage 10mg/kg Q3W.

Timeline

• Start date: 2023-06-29
• Primary completion: 2025-11-01
• Completion: 2026-02-01
• First posted: 2023-05-22
• Last updated: 2025-03-03

Locations

1 site across 1 country: China