## Protocol Section
### Identification Module
**NCT ID:** NCT06424626

**Brief Title:** A Trial of AK104 or AK112 in Combination With Axitinib in Patients With Metastatic Mucosal Melanoma

**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

#### Organization Study ID Info
**ID:** AK104-IIT-043
#### Organization
**Class:** OTHER
**Full Name:** Peking University Cancer Hospital & Institute
### Status Module
#### Completion Date
**Date:** 2027-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-22

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2025-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-05-21

**Type:** ESTIMATED

**Status Verified Date:** 2023-12

#### Study First Post Date
**Date:** 2024-05-22
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-16
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Peking University Cancer Hospital & Institute

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

### Description Module

**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.

**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.

### Conditions Module

**Conditions:**

- Melanoma

- Mucosal Melanoma

- Metastatic Melanoma

**Keywords:**

- Melanoma

- AK104

- AK112

- Mucosal Melanoma

### Design Module

#### Design Info

**Allocation:** NON_RANDOMIZED

**Intervention Model:** PARALLEL

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** 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).

**Intervention Names:**

- Drug: AK104+Axitinib

**Label:** AK104 in Combination With Axitinib

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** 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).

**Intervention Names:**

- Drug: AK112+Axitinib

**Label:** AK112 in Combination With Axitinib

**Type:** EXPERIMENTAL

### Interventions

#### Intervention 1

**Arm Group Labels:**

- AK104 in Combination With Axitinib

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

**Name:** AK104+Axitinib

**Other Names:**

- Cadonilimab

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- AK112 in Combination With Axitinib

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

**Name:** AK112+Axitinib

**Other Names:**

- Ivonescimab

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** Safety assessments including vital signs, laboratory tests, and adverse event monitoring

**Measure:** Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

**Time Frame:** 3 years

#### Secondary Outcomes

**Description:** The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine tumor response.

**Measure:** Objective Response Rate (ORR) by irRC and RECIST 1.1

**Time Frame:** 3 years

**Description:** 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.

**Measure:** Duration of Response (DOR) by irRC and RECIST 1.1

**Time Frame:** 3 years

**Description:** 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.

**Measure:** Disease Control Rate (DCR) by irRC and RECIST 1.1

**Time Frame:** 3 years

**Description:** 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.

**Measure:** Time to response (TTR) by irRC and RECIST 1.1

**Time Frame:** 3 years

**Description:** 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.

**Measure:** Progression-free survival(PFS) by irRC and RECIST 1.1

**Time Frame:** 3 years

**Description:** The treatment effect of AK104 or AK112 in combination with axitinib, will be assessed using irRC and RECIST 1.1 to determine overall survival.

**Measure:** Overall survival (OS) by irRC and RECIST 1.1

**Time Frame:** 3 years

### Eligibility Module

**Eligibility Criteria:** 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

**Maximum Age:** 70 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** silu.net@hotmail.com

**Name:** Lu Si, MD

**Phone:** +86(10)88196951

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Beijing

**Country:** China

**Facility:** Beijing Cancer Hospital

**Zip:** 100142

#### Overall Officials

**Official 1:**

**Affiliation:** Peking University Cancer Hospital & Institute

**Name:** Jun Guo, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000018358

- Term: Neuroendocrine Tumors

- ID: D000017599

- Term: Neuroectodermal Tumors

- ID: D000009373

- Term: Neoplasms, Germ Cell and Embryonal

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000009380

- Term: Neoplasms, Nerve Tissue

- ID: D000018326

- Term: Nevi and Melanomas

- ID: D000012878

- Term: Skin Neoplasms

- ID: D000009371

- Term: Neoplasms by Site

- ID: D000012871

- Term: Skin Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC17

- Name: Skin and Connective Tissue Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M11528

- Name: Melanoma

- Relevance: HIGH

- As Found: Melanoma

- ID: M20495

- Name: Neuroendocrine Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M19845

- Name: Neuroectodermal Tumors

- Relevance: LOW

- As Found: Unknown

- ID: M20388

- Name: Neuroectodermal Tumors, Primitive

- Relevance: LOW

- As Found: Unknown

- ID: M12318

- Name: Neoplasms, Germ Cell and Embryonal

- Relevance: LOW

- As Found: Unknown

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M12325

- Name: Neoplasms, Nerve Tissue

- Relevance: LOW

- As Found: Unknown

- ID: M12448

- Name: Nevus, Pigmented

- Relevance: LOW

- As Found: Unknown

- ID: M12446

- Name: Nevus

- Relevance: LOW

- As Found: Unknown

- ID: M20470

- Name: Nevi and Melanomas

- Relevance: LOW

- As Found: Unknown

- ID: M15681

- Name: Skin Neoplasms

- Relevance: LOW

- As Found: Unknown

- ID: M15674

- Name: Skin Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T4091

- Name: Neuroendocrine Tumor

- Relevance: LOW

- As Found: Unknown

- ID: T4092

- Name: Neuroepithelioma

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000008545

- Term: Melanoma

### Intervention Browse Module - Ancestors

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000047428

- Term: Protein Kinase Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M1910

- Name: Axitinib

- Relevance: HIGH

- As Found: Chamber

- ID: M25820

- Name: Protein Kinase Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000077784

- Term: Axitinib

### Misc Info Module

- Version Holder: 2024-05-31
