A Trial of AK104 or AK112 in Combination With Axitinib in Patients With Metastatic Mucosal Melanoma

Melanoma Clinical Trial

Official title:

A Phase Ib, Open, Mono-center, Dose-reduction Tolerability Study of AK104 or AK112 in Combination With Axitinib in Patients With Metastatic Mucosal Melanoma

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06424626
• Other study ID #: AK104-IIT-043
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: May 21, 2024
• Est. completion date: December 31, 2027

Study information

• Verified date: December 2023
• Source: Peking University Cancer Hospital & Institute
• Contact: Lu Si, MD
• Phone: +86(10)88196951
• Email: silu.net[@]hotmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study was a phase IB, single-center, open-label, two part(part A involved dose reduction, and part B involved cohort expansion) clinical trial evaluating the safety and clinical activity of AK104 or AK112 in combination with axitinib in patients with advanced mucosal melanoma.

Description:

The planned cohorts in part A were axitinib 5mg twice a day plus AK104 or AK112 every 3 weeks. A minimum of three patients were initially enrolled at the first dose level. If a dose-limiting toxicity occurred, then the cohort would be expanded to a total of six patients. Responses were evaluated by investigators using both RECIST version 1.1 and Immune-Related RECIST (irRECIST). Patients with progressive disease or an intolerant toxicity were taken off the study. Patients who initially developed progressive disease per RECIST version 1.1 were allowed to continue therapy if the investigator considered patients to be benefiting from the treatment per irRECIST. Any dose-reduction cohort that did not exceed the maximum-tolerated dose could be expanded in part B for additional evaluation of safety and clinical activity. The primary end point of this study was dose-limiting toxicity within the first 4 weeks of treatment with AK104 or AK112 plus axitinib in part A.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 31, 2027
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1?18 to 70 years old (at the time consent is obtained). 2?Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures). 3?Have histologically- or cytologically-confirmed diagnosis of Metastatic Mucosal Melanoma. 4?Have a life expectancy of at least 3 months 5?Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 6?Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as determined by the site study team 7?Has adequate organ function as defined by:Absolute neutrophil count = 1,500/µL;Platelets = 100,000/µL;Hemoglobin = 9 g/dL;Crcl = 50ml/min creatinine clearance may be calculated using the institutional/laboratory standard method.Serum total bilirubin = 1.5 x ULN ;Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 x ULN ;Albumin =28g/L;International Normalized Ratio (INR) and aPTT <1.5 x ULN. Left ventricular ejection fraction =50%. 8?Have recovered from the effects of any prior radiotherapy or surgery 9?All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria:

1. Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib

2. Is currently participating in a study of an investigational agent or using an investigational device

3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment

4. Has undergone major surgery within 30 days of Study Day 1

5. Has a known additional malignancy that is progressing or requires systemic treatment. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer

6. Has known active central nervous system (CNS) metastases

7. Has carcinomatous meningitis

8. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study

9. Has an active infection requiring systemic therapy

10. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected)

11. History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment

Related Conditions & MeSH terms

• Melanoma
• Metastatic Melanoma
• Mucosal Melanoma

Intervention

Drug:
• AK104+Axitinib
Subjects receive AK104 10mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.
• AK112+Axitinib
Subjects receive AK112 20mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.

Locations

Country	Name	City	State
China	Beijing Cancer Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University Cancer Hospital & Institute

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	Safety assessments including vital signs, laboratory tests, and adverse event monitoring	3 years
Secondary	Objective Response Rate (ORR) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine tumor response.	3 years
Secondary	Duration of Response (DOR) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine duration of response.	3 years
Secondary	Disease Control Rate (DCR) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine disease control rate.	3 years
Secondary	Time to response (TTR) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine time to response.	3 years
Secondary	Progression-free survival(PFS) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine progression-free survival time.	3 years
Secondary	Overall survival (OS) by irRC and RECIST 1.1	The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival.	3 years