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

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma; Metastatic Melanoma; Mucosal Melanoma
• Intervention / Treatment: Drug: AK104+Axitinib; Drug: AK112+Axitinib

Detailed 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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Lu Si, MD; Phone Number: +86(10)88196951; Email: silu.net@hotmail.com

Study Locations

• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AK104 in Combination With Axitinib; The planned cohorts in part A were axitinib 5mg twice a day plus AK104 10mg/kg 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).	Drug: AK104+Axitinib; Subjects receive AK104 10mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.; Other Names: Cadonilimab
Experimental: AK112 in Combination With Axitinib; The planned cohorts in part A were axitinib 5mg twice a day plus AK112 20mg/kg 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).	Drug: AK112+Axitinib; Subjects receive AK112 20mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.; Other Names: Ivonescimab

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Peking University Cancer Hospital & Institute
• Investigators: Principal Investigator: Jun Guo, MD, Peking University Cancer Hospital & Institute

Study record dates

Study Major Dates

• Study Start (Estimated): May 21, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: May 16, 2024
• First Submitted That Met QC Criteria: May 16, 2024
• First Posted (Actual): May 22, 2024

Study Record Updates

• Last Update Posted (Actual): May 22, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Melanoma; Mucosal Melanoma; AK104; AK112
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Melanoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Axitinib
• Other Study ID Numbers: AK104-IIT-043

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No