Safety and Efficacy of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Selected Advanced Solid Tumors

NCT ID: NCT04172454

Last Updated: 2022-10-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-20
• Study Completion Date: 2022-09-23

Brief Summary

A multicenter, open-label, phase 1b/2 study to evaluate the safety and efficacy of AK104, a PD-1 and CTLA-4 bispecific antibody, in selected advanced solid tumors.

Conditions

Advanced Solid Tumors; Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AK104

AK104 in subjects with advanced melanoma and other selected advanced solid tumor including PD-1/PD-L1 relapsed/refractory tumors)

Group Type: EXPERIMENTAL

AK104

Intervention Type: BIOLOGICAL

AK104, 6mg/kg, Q2W

Interventions

AK104

AK104, 6mg/kg, Q2W

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

1. Written and signed informed consent.

2. Male or female, age ≥ 18 years and ≤75, at the time of study entry.

3. Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1

4. Estimated life expectancy of ≥3 months.

5. Histologically or cytologically documented advanced or metastatic melanoma and other selected advanced solid tumors.

6. Subjects must have at least one measurable lesion per RECIST v1.1.

7. Available archived tumor tissue sample to allow for correlative biomarker studies. In the setting where archival material is unavailable or unsuitable for use , the subject must consent and undergo fresh tumor biopsy (biopsy at acceptable risk as judged by the investigator).

8. Adequate organ functions.

9. Female subjects of childbearing potential who are sexually active with a nonsterilized male partner must use an acceptable method of contraception from screening, and must agree to continue using such precautions for 90 days after the final dose of investigational product.

10. Subjects who agree to take effective contraception methods from screening to 120 days after the last dose of investigational product.

11. Willing to follow all the experimental requirements designated by the protocol.

Exclusion Criteria

1. Prior use of investigational products or devices within 4 weeks prior to the first administration of the study treatment.

2. Concurrent enrollment into another clinical study, except the study belongs to investigational, non-interventional studies or the follow-up period of interventional studies.

3. Prior exposure to anti-tumor therapies, including systematic chemotherapy, radiotherapy, immunotherapy, hormone therapy, targeted therapy (within 2 weeks before the first administration of the study treatment), and systematic immune-modulators (including but not limited to interferon, interleukin-2 and tumor necrosis factor) within 4 weeks prior to the first administration of the study treatment. Prior exposure to Chinese herbal medicine or proprietary Chinese medicine with anti-tumor functions within 2 weeks prior to the first administration of the study treatment.

5. For subjects previously treated with anti-PD-1, PD-L1 or other immunotherapies: (1) Subjects have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. (2) All AEs while receiving prior immunotherapy have not completely resolved or resolved to Grade 1 prior to screening for this study. (3) Subjects have required the use of additional immunosuppression other than corticosteroids for the management of an AE, or have experienced recurrence of an AE if re-challenged with corticosteroids while receiving prior immunotherapy.

6. Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with some exceptions.

7. Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).

8. Prior use of systematic corticosteroid (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to the first administration of the study treatment.

9. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.

10. Prior exposure to major surgery within 28 days prior to the first administration of the study treatment. Local procedures (eg, placement of a systemic port, core needle biopsy, and prostate biopsy) are allowed if completed at least 24 hours prior to the administration of the first dose of study treatment.

11. Known history of interstitial lung disease. The subjects highly suspected of interstitial lung disease will be excluded. Subjects with severe lung diseases affecting lung functions will be excluded.

12. Known history of active tuberculosis (TB). Subjects suspected of having active TB will be examined with x-ray, sputum, and clinical symptoms.

13. Known history of primary immunodeficiency virus infection or known history of testing positive for human immunodeficiency virus (HIV).

14. Subjects with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) DNA exceeding 1000 IU/ mL or active hepatitis C virus (HCV) should be excluded. Subjects with positive HCV antibodies are eligible only if the HCV RNA test results are negative.

15. Serious infections within 4 weeks prior to the first dose of study drug.

16. Receipt of live, attenuated vaccination within 30 days prior to the first dose of study treatment, or plan to receive live, attenuated vaccine during the study.

17. Known history of sever hypersensitivity reaction to other monoclonal antibodies.

18. Known history of allergy or hypersensitivity to AK104 or any of its components

19. Any conditions that, in the investigator's opinion, may put subjects treated with the study drug at risks, or interfere with the evaluation of study drug or subject safety, or the interpretation of results.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso Pharmaceuticals, Inc.

OTHER

Sponsor Role: collaborator

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Li Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Xiaoshi Zhang, MD

Role: PRINCIPAL_INVESTIGATOR

Sun Yat-sen University

Locations

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, China

Countries

China

References

Zhao Y, Ma Y, Fan Y, Zhou J, Yang N, Yu Q, Zhuang W, Song W, Wang ZM, Li B, Xia Y, Zhao H, Zhang L. A multicenter, open-label phase Ib/II study of cadonilimab (anti PD-1 and CTLA-4 bispecific antibody) monotherapy in previously treated advanced non-small-cell lung cancer (AK104-202 study). Lung Cancer. 2023 Oct;184:107355. doi: 10.1016/j.lungcan.2023.107355. Epub 2023 Aug 29.

Reference Type: DERIVED

PMID: 37677918 (View on PubMed)

Other Identifiers

AK104-202

Identifier Type: -

Identifier Source: org_study_id