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

NCT05868876 | Recruiting Phase 1

• 1 other identifier: AK127-103
• Study Type: interventional
• Target: 205
• Locations: 1 country
• Sites: 1

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

Conditions

Advanced Malignant Tumors

Outcome Measures

Primary Outcomes (7)

• Incidence and severity of adverse events(AE);

  Incidence and severity of AEs is aim to evaluate the safety of AK127 and AK104

  Up to approximately 2 years

• Incidence of serious adverse events(SAE);

  Incidence of SAE is aim to evaluate the safety of AK127 and AK104.

  Up to approximately 2 years

• Incidence of immune-related adverse events(irAE);

  Incidence of irAE is aim to evaluate the safety of AK127 and AK104.

  Up to approximately 2 years

• The incidence of suspected unexpected serious adverse reactions(SUSAR);

  The incidence of SUSAR is aim to evaluate the safety of AK127 and AK104.

  Up to approximately 2 years

• Incidence of dose-limiting toxicity(DLT);

  The purpose of DLT is to find the Phase II recommended dose(RP2D) or MTD.

  Up to approximately 2 years

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

  Monitor and summerize all data derive from clinically significant changes in laboratory assessment data per Common Terminology Criteria for Adverse Events(CTCAE)5.0.

  Up to approximately 2 years

• AE that leads to the termination or suspension of treatment.

  AE that leads to the termination or suspension of treatment is aim to evaluate the safety of AK127 and AK104.

  Up to approximately 2 years

Secondary Outcomes (14)

• Objective response rate(ORR)

  Up to approximately 2 years

• Disease control rate(DCR)

  Up to approximately 2 years

• duration of response(DoR)

  Up to approximately 2 years

• time to response(TTR)

  Up to approximately 2 years

• progression-free survival(PFS)

  Up to approximately 2 years

Study Arms (1)

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

EXPERIMENTAL

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.

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

Interventions

AK127 Q3W IV infusion ,AK104 10mg/kg Q3W IV infusion DRUG

AK127 is administered intravenously according to the frequency Q3W and different dosage of administration at different stages.AK104 is administered intravenously according to the frequency and dosage 10mg/kg Q3W.

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

• 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.
• \. 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. 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.
• \. 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.

You may not qualify if:

• \. 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. 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.
• \. 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.
• \. 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.
• \. 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 .
• \. 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.
• \. 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 .
• \. Systolic blood pressure ≥150 mmHg or diastolic blood pressure ≥100 mmHg after oral antihypertensive medication with present hypertension.
• \. Hyperglycemia that has not been controlled by treatment. 16. Pleural effusion, pericardial effusion or ascites with clinical symptoms or requiring repeated drainage.
• \. There is a history of noninfectious pneumonia requiring systemic glucocorticoid therapy or a current interstitial lung disease.
• \. 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.
• \. Known history of allogeneic organ transplantation and hematopoietic stem cell transplantation.
• \. Known allergy to any component of any study drug; known history of severe hypersensitivity to other monoclonal antibodies.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Tianjin Cancer Hospital

Tianjin, Tianjin Municipality, 300060, China

RECRUITING

Study Officials

• Jihui Hao, Doctor

  Tianjin Cancer Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xiao Xu, MD, PhD

CONTACT

+86 (0760) 8987 3999; clinicaltrials@akesobio.com

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: May 11, 2023
• First Posted: May 22, 2023
• Study Start: June 29, 2023
• Primary Completion: November 1, 2025
• Study Completion: February 1, 2026
• Last Updated: March 3, 2025

Record last verified: 2025-02

Locations

CN (1)