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

A Multicenter, Open-label,Phase 1b/2 Study for Safety and Efficacy of AK104, a PD-1/CTLA-4 Bispecific Antibody, in Selected Advanced Solid Tumors

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.

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.
4. Unresolved toxicities from prior anticancer therapy, defined as having not resolved to NCI CTCAE v5.0 Grade 0 or 1, or to levels dictated in the inclusion/exclusion criteria. Hair loss is excluded.
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.