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

NCT04172454 | Completed Phase 1

• 1 other identifier: AK104-202
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

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

Keywords

Bispecific; PD1/CTLA4; PD-1/PD-L1 relapsed/refractory tumors

Outcome Measures

Primary Outcomes (1)

• Anti-tumor activity of AK104 using objective response rate (ORR) based on RECIST v1.1 as assessed by the investigator

  The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1.

  Up to 2 years

Secondary Outcomes (7)

• Number of subjects experiencing adverse events (AEs)

  From the time of informed consent through 90 days after last dose of AK104

• Disease control rate (DCR)

  Up to 2 years

• Progression-free survival (PFS)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Duration of response (DoR)

  Up to 2 years

Study Arms (1)

AK104

EXPERIMENTAL

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

Biological: AK104

Interventions

AK104 BIOLOGICAL

AK104, 6mg/kg, Q2W

AK104

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written and signed informed consent.
• Male or female, age ≥ 18 years and ≤75, at the time of study entry.
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Estimated life expectancy of ≥3 months.
• Histologically or cytologically documented advanced or metastatic melanoma and other selected advanced solid tumors.
• Subjects must have at least one measurable lesion per RECIST v1.1.
• 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).
• Adequate organ functions.
• 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.
• Subjects who agree to take effective contraception methods from screening to 120 days after the last dose of investigational product.
• Willing to follow all the experimental requirements designated by the protocol.

You may not qualify if:

• Prior use of investigational products or devices within 4 weeks prior to the first administration of the study treatment.
• Concurrent enrollment into another clinical study, except the study belongs to investigational, non-interventional studies or the follow-up period of interventional studies.
• 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.
• 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.
• Subjects with active, known or suspected autoimmune disease, or a medical history of autoimmune disease, with some exceptions.
• Active or previously documented inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis or chronic diarrhea).
• 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.
• Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation.
• 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.
• 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.
• Known history of active tuberculosis (TB). Subjects suspected of having active TB will be examined with x-ray, sputum, and clinical symptoms.
• Known history of primary immunodeficiency virus infection or known history of testing positive for human immunodeficiency virus (HIV).
• 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.
• Serious infections within 4 weeks prior to the first dose of study drug.
• 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.

Sponsors & Collaborators

• Akeso: lead
• Akeso Pharmaceuticals, Inc.: collaborator

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guangzhou, Guangdong, 510030, China

Location

Related Publications (1)

• 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.

  PMID: 37677918 DERIVED

MeSH Terms

Conditions

Melanoma; Neoplasms

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Li Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

• Xiaoshi Zhang, MD

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: November 21, 2019
• Study Start: December 20, 2019
• Primary Completion: June 17, 2021
• Study Completion: September 23, 2022
• Last Updated: October 12, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)