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

NCT06424626 | Not Yet Recruiting Phase 1

• 1 other identifier: AK104-IIT-043
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Melanoma; Mucosal Melanoma; Metastatic Melanoma

Keywords

Melanoma; AK104; AK112; Mucosal Melanoma

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Objective Response Rate (ORR) by irRC and RECIST 1.1

  3 years

• Duration of Response (DOR) by irRC and RECIST 1.1

  3 years

• Disease Control Rate (DCR) by irRC and RECIST 1.1

  3 years

• Time to response (TTR) by irRC and RECIST 1.1

  3 years

• Progression-free survival(PFS) by irRC and RECIST 1.1

  3 years

Study Arms (2)

AK104 in Combination With Axitinib

EXPERIMENTAL

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

AK112 in Combination With Axitinib

EXPERIMENTAL

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

Interventions

AK104+Axitinib DRUG

Subjects receive AK104 10mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.

Also known as: Cadonilimab

AK104 in Combination With Axitinib

AK112+Axitinib DRUG

Subjects receive AK112 20mg/kg intravenously (IV) every 3-week cycle plus Axitinib until progression.

Also known as: Ivonescimab

AK112 in Combination With Axitinib

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 、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).
• 、Have histologically- or cytologically-confirmed diagnosis of Metastatic Mucosal Melanoma.
• 、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%.
• 、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.

You may not qualify if:

• Prior treatment with anti-PD-1/PD-L1/PD-L2 antibody and Axitinib
• Is currently participating in a study of an investigational agent or using an investigational device
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment
• Has undergone major surgery within 30 days of Study Day 1
• 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
• Has known active central nervous system (CNS) metastases
• Has carcinomatous meningitis
• 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
• Has an active infection requiring systemic therapy
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected)
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment

Sponsors & Collaborators

• Peking University Cancer Hospital & Institute: lead

Study Sites (1)

Beijing Cancer Hospital

Beijing, 100142, China

Location

MeSH Terms

Conditions

Melanoma

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Jun Guo, MD

  Peking University Cancer Hospital & Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lu Si, MD

CONTACT

+86(10)88196951; silu.net@hotmail.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: May 21, 2024
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2027
• Last Updated: May 22, 2024

Record last verified: 2023-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)