AK129 Combination Therapy for Advanced Solid Tumors

NCT ID: NCT06943820

Last Updated: 2025-06-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 230 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-21
• Study Completion Date: 2028-05-31

Brief Summary

This is an open, multicenter phase Ib/II clinical study. The goal of this study is to confirm the Phase II recommended dose (RP2D) of AK129 combinations for advanced solid tumors and evaluate the safety and efficacy of AK129 combinations for non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), colorectal adenocarcinoma (CRC), and other advanced solid tumors.

Conditions

Non-small Cell Lung Cancer Stage IIIB/IV; Head and Neck Squamous Cell Carcinoma (HNSCC); Colorectal Adenocarcinoma; Advanced Solid Tumors

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AK129(dose 1) + Chemotherapy(Phase Ib)

Non-Squamous NSCLC:Subjects receive AK129 (dose 1) plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(dose 1) plus Pemetrexed until progression.

Squamous NSCLC:Subjects receive AK129 (dose 1) plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(dose 1) until progression.

Group Type: EXPERIMENTAL

AK129(dose 1)

Intervention Type: DRUG

IV infusion

Pemetrexed

Intervention Type: DRUG

IV infusion;500mg/m2

Paclitaxel

Intervention Type: DRUG

IV infusion;175mg/m2

Carboplatin

Intervention Type: DRUG

IV infusion;AUC 5

AK129(dose 2) + Chemotherapy(Phase Ib)

Non-Squamous NSCLC:Subjects receive AK129 (dose 2) plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(dose 2) plus Pemetrexed until progression.

Squamous NSCLC:Subjects receive AK129(dose 2) plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(dose 2) until progression.

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

IV infusion;500mg/m2

Paclitaxel

Intervention Type: DRUG

IV infusion;175mg/m2

Carboplatin

Intervention Type: DRUG

IV infusion;AUC 5

AK129(dose 2)

Intervention Type: DRUG

IV infusion

Cohort 1 PARTA Treatment Group 1(Phase II)

Non-Squamous NSCLC:Subjects receive AK129 (RP2D) plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(RP2D) plus Pemetrexed until progression.

Squamous NSCLC:Subjects receive AK129(RP2D) plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK129(RP2D) until progression.

Group Type: EXPERIMENTAL

Pemetrexed

Intervention Type: DRUG

IV infusion;500mg/m2

Paclitaxel

Intervention Type: DRUG

IV infusion;175mg/m2

Carboplatin

Intervention Type: DRUG

IV infusion;AUC 5

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Cohort 1 PARTA Treatment Group 2(Phase II)

Non-Squamous NSCLC:Subjects receive Penpulimab plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by Penpulimab plus Pemetrexed until progression.

Squamous NSCLC:Subjects receive Penpulimab plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by Penpulimab until progression.

Group Type: ACTIVE_COMPARATOR

Pemetrexed

Intervention Type: DRUG

IV infusion;500mg/m2

Paclitaxel

Intervention Type: DRUG

IV infusion;175mg/m2

Carboplatin

Intervention Type: DRUG

IV infusion;AUC 5

Penpulimab

Intervention Type: DRUG

IV infusion;200mg

Cohort 1 PARTB(Phase II)

NSCLC:Subjects receive AK129(RP2D) plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

IV infusion;75mg/m2

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Cohort 2 PARTA(Phase II)

HNSCC:Subjects receive AK129(RP2D,Day1) plus Carboplatin/Cis-platinum(Day1) and 5-FU(Day1-4) every 3-week cycle (Q3W) for 6 cycles followed by AK129(RP2D) until progression.

Group Type: EXPERIMENTAL

Carboplatin

Intervention Type: DRUG

IV infusion;AUC 5

Cis-platinum

Intervention Type: DRUG

IV infusion;100 mg/m2

5-FU (5-fluorouracil)

Intervention Type: DRUG

IV infusion;1000 mg/m2

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Cohort 2 PARTB(Phase II)

HNSCC:Subjects receive AK129(RP2D) plus 1 investigator-selected treatment protocol(Cetuximab/Paclitaxel/Docetaxel) on Day 1 of every 3-week cycle (Q3W) until progression, and are not allowed to choose a treatment they had already received.

Group Type: EXPERIMENTAL

Cetuximab

Intervention Type: DRUG

IV infusion;400mg/m2/ 250mg/m2

Paclitaxel

Intervention Type: DRUG

IV infusion;80mg/m2

Docetaxel

Intervention Type: DRUG

IV infusion;35mg/m2

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Cohort 3(Phase II)

CRC:Subjects receive AK129(RP2D) until progression.

Group Type: EXPERIMENTAL

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Cohort 4(Phase II)

Advanced solid tumors:Subjects receive AK129(RP2D)± chemotherapy until progression.

Group Type: EXPERIMENTAL

Chemotherapy

Intervention Type: DRUG

IV infusion

AK129(RP2D)

Intervention Type: DRUG

IV infusion

Interventions

AK129(dose 1)

IV infusion

Intervention Type: DRUG

Pemetrexed

IV infusion;500mg/m2

Intervention Type: DRUG

Paclitaxel

IV infusion;175mg/m2

Intervention Type: DRUG

Carboplatin

IV infusion;AUC 5

Intervention Type: DRUG

AK129(dose 2)

IV infusion

Intervention Type: DRUG

Docetaxel

IV infusion;75mg/m2

Intervention Type: DRUG

Cis-platinum

IV infusion;100 mg/m2

Intervention Type: DRUG

5-FU (5-fluorouracil)

IV infusion;1000 mg/m2

Intervention Type: DRUG

Cetuximab

IV infusion;400mg/m2/ 250mg/m2

Intervention Type: DRUG

Paclitaxel

IV infusion;80mg/m2

Intervention Type: DRUG

Docetaxel

IV infusion;35mg/m2

Intervention Type: DRUG

Chemotherapy

IV infusion

Intervention Type: DRUG

AK129(RP2D)

IV infusion

Intervention Type: DRUG

Penpulimab

IV infusion;200mg

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures);

2. ≥18 years old and ≤ 75 years (regardless of sex);

3. ECOG performance status 0-1;

4. Life expectancy longer than 3 months;

5. 1)Histologically or cytologically confirmed diagnosis of Stage IIIB/C or IV NSCLC (American Joint Committee on Cancer [AJCC]); 2)No prior systemic anti-tumor therapy for locally advanced or metastatic NSCLC;must have received a platinum-based combination therapy and a PD-(L)1 monoclonal antibody for the treatment of locally advanced or metastatic disease and progressed during or after receiving prior therapy;

6. 1)Histologically or cytologically confirmed diagnosis of recurrent or metastatic HNSCC (American Joint Committee on Cancer [AJCC]); 2)No prior systemic anti-tumor therapy for recurrent or metastatic HNSCC ;must have received a platinum-based combination therapy and a PD-(L)1 monoclonal antibody for the treatment of recurrent or metastatic disease and progressed during or after receiving prior therapy;

7. Histologically or cytologically confirmed diagnosis of advanced colorectal adenocarcinoma with microsatellite stabilization;

8. Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;

9. Adequate organ function.

Exclusion Criteria

1. Histologically or cytologically confirmed the presence of small cell carcinoma components/EGFR-sensitive mutations or ALK fusion positivite/known ROS1 rearrangement, MET exon 14 skipping mutation, EGFR exon 20 insertion mutation, BRAF V600E mutation, NTRK gene fusion positivite or RET gene fusion positivite;

2. Histologically or cytologically confirmed diagnosis of advanced colorectal adenocarcinoma with microsatellite highly unstable/mismatch repair gene expression defect (MSI-H/dMMR)or histopathological examination confirmed other pathological types;

3. Participating in another clinical research;

4. Has known active central nervous system (CNS) metastases, brain stem/meningeal metastasis, spinal cord metastasis or compression;

5. Has an active autoimmune disease that has required systemic treatment in the past 2 years;

6. Has known active tuberculosis (TB) and suspected active TB should be ruled out by clinical examination; known active syphilis infection; known active Hepatitis B or Hepatitis C;

7. Past or currently has non-infectious pneumonia/interstitial lung disease that requires systemic glucocorticoid therapy;

8. Has pleural effusion, pericardial effusion, or ascites that have clinical symptoms or require repeated drainage;

9. Had a history of myocarditis, cardiomyopathy, and malignant arrhythmia;

10. Has known allergy to any component of any investigational drug; a known history of severe hypersensitivity to other monoclonal antibodies;

11. Pregnant or lactating female.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Liaoning Cancer Hospital

Shenyang, Liaoning, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wenting Li,M.D.

Role: CONTACT

clinicaltrials@akesobio.com

+86(0760)89873999

Hongxu Liu,M.D.

Role: CONTACT

Hongxuliu@qq.com

Other Identifiers

AK129-201

Identifier Type: -

Identifier Source: org_study_id