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

Akeso1 site in 1 country205 target enrollmentJune 29, 2023

ConditionsAdvanced Malignant Tumors

InterventionsAK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion

DrugsAK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion

Overview

Phase: Phase 1
Intervention: AK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion
Conditions: Advanced Malignant Tumors
Sponsor: Akeso
Enrollment: 205
Locations: 1
Primary Endpoint: Number of participants with clinically significant changes in laboratory assessment data as assessed by CTCAE v5.0.
Status: Recruiting
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief 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.

Registry

clinicaltrials.gov

Start Date

June 29, 2023

End Date

February 2026

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Akeso

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•1.The subject must sign the written informed consent form(ICF) voluntarily. 2.Aged ≥ 18 to ≤ 75 years,male and female at the time of enrollment. 3.Eastern Cooperative Oncology Group(ECOG) performance status score of 0 or
•4.Life expectancy≥ 3 months. 5.Patients with histologically or cytologically confirmed advanced, recurrent, or metastatic malignancies were enrolled in the phase Ia dose escalation phase;Selected tumor species were enrolled in phase Ib dose extension.Patients with advanced metastatic malignancies who have failed first-line, or second-line, or third-line, or fourth-line standard therapies, or who not appropriate for standard treatment, cannot tolerate chemotherapy, or do not have effective standard therapies.
•According to RECIST v1.1, there is at least one measurable lesion, and the lesion is suitable for repeated accurate measurement;Brain metastases cannot be used as target foci.
•Good organ function.
•The serum pregnancy test results of female subjects in the child-bearing age within 3 days before the first medication were negative;
•If a fertile female subject has sex with an unsterilized male partner, the subject must begin from screening for effective contraceptive methods and must agree to continue using these precautions until 6 months after the last administration of the study drug;Periodic abstinence, safe period contraception and external ejaculation are not acceptable contraceptive methods.
•If an unsterilized male subject has sexual intercourse with a fertile female partner, the subject must use an effective contraceptive method from the beginning of screening to within 6 months after the last dose.

Exclusion Criteria

•Previous treatment for:Use of small-molecule targeted antitumor drugs, monoclonal or double-clonal antibodies targeting PD-(L)1 or CTLA-4, other anti-tumor antibodies, other anti-tumor therapies (e.g., chemotherapy, radiotherapy, biological or hormonal therapy) within 4 weeks prior to initial administration of the study drug, previous use of immunomodulatory drugs within 2 weeks prior to initial administration of the study drug,Prior treatment with approved or investigational TIGIT antibodies, PVRIG antibodies, or CD96 antibodies.
•Enroll in another clinical study at the same time.
•Received other antitumor therapy 4 weeks before the first administration or 5 half-lives of the drug (whichever is shorter) : e.g. palliative local therapy for non-target lesions was performed within 2 weeks before the first administration;Received non-specific immunomodulatory therapy within 2 weeks prior to initial administration;Received Chinese herbal medicine or Chinese patent medicine with anti-tumor indications within 1 week prior to initial administration.
•Central nervous system metastasis with clinical symptoms.
•Other malignancies within 3 years prior to the first medication.
•Active autoimmune disease requiring systemic treatment within 2 years prior to initial medication.
•History of serious disease within 1 year before the first medication.
•History of gastrointestinal perforation and/or fistula, history of gastrointestinal obstruction, and extensive enterectomy within 6 months prior to initial administration.
•Patients receiving chest radiotherapy \>30 Gy within 6 months before the first drug use, non-chest radiotherapy \>30 Gy within 4 weeks before the first drug use, and palliative radiotherapy ≤30 Gy within 2 weeks before the first drug use.Subjects who did not recover from toxicity and/or complications from these interventions to NCI CTCAE grade ≤1 (except hair loss and fatigue).
•Live or attenuated vaccine has been administered within 4 weeks prior to initial administration, or if it is planned to be administered during the study period. Inactivated vaccine is permitted .

Arms & Interventions

The dose escalation stage, dose expansion stage of AK127 combination with AK104

The dose escalation stage： 5 dose groups were set up, which were 0.3mg/kg、1 mg/kg, 3 mg/kg, 7.5 mg/kg, 15 mg/kg Q3W in dose escalation stage; The dose expansion stage： 8 cohorts with different indications were included in each group with 10-20 subjects in dose expansion stage.

Intervention: AK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion

Outcomes

Primary Outcomes

Number of participants with clinically significant changes in laboratory assessment data as assessed by CTCAE v5.0.