AK129 Combination Therapy for Advanced Solid Tumors

Phase 1

Not yet recruiting

• Conditions: Non-small Cell Lung Cancer Stage IIIB/IV; Head and Neck Squamous Cell Carcinoma (HNSCC); Colorectal Adenocarcinoma; Advanced Solid Tumors
• Interventions: Drug: Pemetrexed; Drug: Cetuximab; Drug: Chemotherapy; Drug: AK129(dose 1); Drug: Cis-platinum; Drug: Carboplatin; Drug: Paclitaxel; Drug: 5-FU (5-fluorouracil); Drug: Docetaxel; Drug: AK129(dose 2); Drug: AK129(RP2D); Drug: Penpulimab

• Registration Number: NCT06943820
• Lead Sponsor: Akeso

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.

Detailed Description

Not available

Study Timeline

• Status Verified: 2025-04
• Study First Submitted: 2025-04-06
• Study First Submitted QC: 2025-04-17
• Last Update Submitted: 2025-04-17
• Study First Posted: 2025-04-24
• Last Update Posted: 2025-04-24
• Study Start: 2025-05
• Primary Completion: 2026-12
• Study Completion: 2028-05

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 230

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
AK129(dose 2) + Chemotherapy(Phase Ib)	AK129(dose 2)	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.
Cohort 1 PARTA Treatment Group 1(Phase II)	Carboplatin	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.
AK129(dose 1) + Chemotherapy(Phase Ib)	Paclitaxel	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.
AK129(dose 1) + Chemotherapy(Phase Ib)	Carboplatin	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.
AK129(dose 2) + Chemotherapy(Phase Ib)	Pemetrexed	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.
AK129(dose 2) + Chemotherapy(Phase Ib)	Paclitaxel	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.
AK129(dose 2) + Chemotherapy(Phase Ib)	Carboplatin	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.
Cohort 1 PARTA Treatment Group 1(Phase II)	Pemetrexed	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.
Cohort 1 PARTA Treatment Group 2(Phase II)	Pemetrexed	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.
Cohort 1 PARTA Treatment Group 1(Phase II)	Paclitaxel	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.
Cohort 1 PARTA Treatment Group 1(Phase II)	AK129(RP2D)	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.
Cohort 1 PARTA Treatment Group 2(Phase II)	Paclitaxel	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.
Cohort 1 PARTA Treatment Group 2(Phase II)	Carboplatin	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.
Cohort 1 PARTA Treatment Group 2(Phase II)	Penpulimab	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.
Cohort 2 PARTA(Phase II)	Carboplatin	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.
Cohort 2 PARTA(Phase II)	Cis-platinum	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.
Cohort 2 PARTA(Phase II)	5-FU (5-fluorouracil)	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.
Cohort 2 PARTA(Phase II)	AK129(RP2D)	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.
Cohort 2 PARTB(Phase II)	Cetuximab	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.
Cohort 2 PARTB(Phase II)	Paclitaxel	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.
Cohort 2 PARTB(Phase II)	Docetaxel	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.
Cohort 2 PARTB(Phase II)	AK129(RP2D)	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.
Cohort 3(Phase II)	AK129(RP2D)	CRC:Subjects receive AK129(RP2D) until progression.
Cohort 4(Phase II)	Chemotherapy	Advanced solid tumors:Subjects receive AK129(RP2D)± chemotherapy until progression.
Cohort 4(Phase II)	AK129(RP2D)	Advanced solid tumors:Subjects receive AK129(RP2D)± chemotherapy until progression.
AK129(dose 1) + Chemotherapy(Phase Ib)	AK129(dose 1)	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.
Cohort 1 PARTB(Phase II)	Docetaxel	NSCLC:Subjects receive AK129(RP2D) plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.
Cohort 1 PARTB(Phase II)	AK129(RP2D)	NSCLC:Subjects receive AK129(RP2D) plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.
AK129(dose 1) + Chemotherapy(Phase Ib)	Pemetrexed	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.

Primary Outcome Measures

Name	Time	Method
Frequency and severity of adverse events (AEs) ,Clinically significant abnormal laboratory results	Up to approximately 2 years	Frequency and severity of AEs and clinically significant abnormal laboratory results for all arms in phase Ib/II.
Overall Response Rate (ORR)	Up to approximately 2 years	ORR is the proportion of subjects with complete response(CR) or partial response(PR) for all arms in phase II , based on RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Response Rate (ORR)	Up to approximately 2 years	ORR is the proportion of subjects with complete response(CR) or partial response(PR) for all arms in phase Ib, based on RECIST v1.1.
Progression-Free Survival (PFS)	Up to approximately 2 years	Evaluation of PFS based on RECIST v1.1.
Overall survival (OS)	Up to approximately 2 years	Evaluation of OS based on RECIST v1.1.
Disease control rate (DCR)	Up to approximately 2 years	Evaluation of DCR based on RECIST v1.1.
Duration of Response (DoR)	Up to approximately 2 years	Evaluation of DoR based on RECIST v1.1.
Time to Response (TTR)	Up to approximately 2 years	Evaluation of TTR based on RECIST v1.1.
Pharmacokinetics (PK)	Up to cycle 21(each cycle is 21 days)	PK parameters: serum concentrations of AK129 at different point of time
Anti-Drug Antibodies(ADAs)	Up to approximately 2 years	Number and percentage of patients with detectable anti-drug antibodies

Trial Locations

Locations (1)

Liaoning Cancer Hospital; 🇨🇳 Shenyang, Liaoning, China