Evaluating AK127 and AK104 for advanced malignant tumors

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

This study is testing two new immunotherapy drugs, AK127 and AK104, to see if they can help people with advanced cancer who haven't responded to other treatments.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 205 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Akeso (Industry-sponsored)
• Drugs / interventions: chemotherapy, Cardonilimab, immunotherapy
• Locations: 1 site (Tianjin, Tianjin Municipality)
• Trial ID: NCT05868876 on ClinicalTrials.gov

What this trial studies

This clinical study assesses the safety, tolerability, and preliminary efficacy of two immunotherapy agents, AK127 and AK104, in patients with advanced malignant tumors. AK104 is a bispecific antibody that targets PD-1 and CTLA-4, while AK127 is designed to block the TIGIT pathway, potentially enhancing the immune response against tumors. The study includes a dose escalation phase followed by a dose extension phase, focusing on patients who have not responded to standard therapies. Participants will receive intravenous infusions of both agents every three weeks.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with advanced, recurrent, or metastatic malignancies that have failed previous treatments.

Not a fit: Patients with brain metastases or those who are not suitable for the study's inclusion criteria may not benefit from this treatment.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced malignant tumors who have limited responses to current immunotherapies.

How similar studies have performed: While the combination of these specific agents is novel, similar immunotherapy approaches have shown promise in other studies.

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 1. 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.

  6\. 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.

  7\. Good organ function. 8. The serum pregnancy test results of female subjects in the child-bearing age within 3 days before the first medication were negative; 9. 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.

  10\. 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:

* 1\. 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.

  2\. Enroll in another clinical study at the same time. 3. 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.

  4\. Central nervous system metastasis with clinical symptoms. 5. Other malignancies within 3 years prior to the first medication. 6. Active autoimmune disease requiring systemic treatment within 2 years prior to initial medication.

  7\. History of serious disease within 1 year before the first medication. 8. History of gastrointestinal perforation and/or fistula, history of gastrointestinal obstruction, and extensive enterectomy within 6 months prior to initial administration.

  9\. 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).

  10\. 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 .

  11\. Severe infection occurs within 4 weeks prior to first dosing. 12. Those who have had major surgical operations or severe trauma within 4 weeks prior to the first dosing, or have major surgical operations planned within 4 weeks after the first dosing; Minor local surgery was performed within 3 days prior to first dosing.

  13\. History of severe bleeding tendency or coagulopathy;There were clinically significant bleeding symptoms, including but not limited to gastrointestinal bleeding, hemoptysis, and nasal bleeding, within 4 weeks prior to first dosing .

  14\. Systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive medication with present hypertension.

  15\. Hyperglycemia that has not been controlled by treatment. 16. Pleural effusion, pericardial effusion or ascites with clinical symptoms or requiring repeated drainage.

  17\. There is a history of noninfectious pneumonia requiring systemic glucocorticoid therapy or a current interstitial lung disease.

  18\. Active or have a clear history of inflammatory bowel disease. 19.History of immune deficiency; HIV antibody positive; Systemic corticosteroid hormones or other immunosuppressants are currently being used long-term.

  20\. Known history of allogeneic organ transplantation and hematopoietic stem cell transplantation.

  21\. Untreated subjects with active hepatitis B;Active hepatitis C subjects. 22. No remission of toxicity from previous antitumor therapy, defined as failure to return to the grade 1 level of toxicity defined in NCI, CTCAE 5.0 or below, or the inclusion/exclusion criteria, with the exception of alopecia and fatigue.

  23\. Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies.

Where this trial is running

Tianjin, Tianjin Municipality

• Tianjin Cancer Hospital — Tianjin, Tianjin Municipality, China (Recruiting)

Study contacts

• Principal investigator: Jihui Hao, Doctor — Tianjin Cancer Hospital
• Study coordinator: Xiao Xu, MD, PhD

Conditions Advanced Malignant Tumors