AK129 Combination Therapy for Advanced Solid Tumors

NCT06943820 | Recruiting Phase 1

• 1 other identifier: AK129-201
• Study Type: interventional
• Target: 230
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of adverse events (AEs) ,Clinically significant abnormal laboratory results

  Frequency and severity of AEs and clinically significant abnormal laboratory results for all arms in phase Ib/II.

  Up to approximately 2 years

• Overall Response Rate (ORR)

  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.

  Up to approximately 2 years

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  Up to approximately 2 years

• Progression-Free Survival (PFS)

  Up to approximately 2 years

• Overall survival (OS)

  Up to approximately 2 years

• Disease control rate (DCR)

  Up to approximately 2 years

• Duration of Response (DoR)

  Up to approximately 2 years

Study Arms (9)

AK129(dose 1) + Chemotherapy(Phase Ib)

EXPERIMENTAL

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.

Drug: AK129(dose 1); Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin

AK129(dose 2) + Chemotherapy(Phase Ib)

EXPERIMENTAL

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.

Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin; Drug: AK129(dose 2)

Cohort 1 PARTA Treatment Group 1(Phase II)

EXPERIMENTAL

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.

Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin; Drug: AK129(RP2D)

Cohort 1 PARTA Treatment Group 2(Phase II)

ACTIVE COMPARATOR

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.

Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin; Drug: Penpulimab

Cohort 1 PARTB(Phase II)

EXPERIMENTAL

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

Drug: Docetaxel; Drug: AK129(RP2D)

Cohort 2 PARTA(Phase II)

EXPERIMENTAL

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.

Drug: Carboplatin; Drug: Cis-platinum; Drug: 5-FU (5-fluorouracil); Drug: AK129(RP2D)

Cohort 2 PARTB(Phase II)

EXPERIMENTAL

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.

Drug: Cetuximab; Drug: Paclitaxel; Drug: Docetaxel; Drug: AK129(RP2D)

Cohort 3(Phase II)

EXPERIMENTAL

CRC:Subjects receive AK129(RP2D) until progression.

Drug: AK129(RP2D)

Cohort 4(Phase II)

EXPERIMENTAL

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

Drug: Chemotherapy; Drug: AK129(RP2D)

Interventions

AK129(dose 1) DRUG

IV infusion

AK129(dose 1) + Chemotherapy(Phase Ib)

Pemetrexed DRUG

IV infusion;500mg/m2

AK129(dose 1) + Chemotherapy(Phase Ib); AK129(dose 2) + Chemotherapy(Phase Ib); Cohort 1 PARTA Treatment Group 1(Phase II); Cohort 1 PARTA Treatment Group 2(Phase II)

Paclitaxel DRUG

IV infusion;175mg/m2

AK129(dose 1) + Chemotherapy(Phase Ib); AK129(dose 2) + Chemotherapy(Phase Ib); Cohort 1 PARTA Treatment Group 1(Phase II); Cohort 1 PARTA Treatment Group 2(Phase II)

Carboplatin DRUG

IV infusion;AUC 5

AK129(dose 1) + Chemotherapy(Phase Ib); AK129(dose 2) + Chemotherapy(Phase Ib); Cohort 1 PARTA Treatment Group 1(Phase II); Cohort 1 PARTA Treatment Group 2(Phase II); Cohort 2 PARTA(Phase II)

AK129(dose 2) DRUG

IV infusion

AK129(dose 2) + Chemotherapy(Phase Ib)

Docetaxel DRUG

IV infusion;75mg/m2

Cohort 1 PARTB(Phase II)

Cis-platinum DRUG

IV infusion;100 mg/m2

Cohort 2 PARTA(Phase II)

5-FU (5-fluorouracil) DRUG

IV infusion;1000 mg/m2

Cohort 2 PARTA(Phase II)

Cetuximab DRUG

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

Cohort 2 PARTB(Phase II)

Chemotherapy DRUG

IV infusion

Cohort 4(Phase II)

AK129(RP2D) DRUG

IV infusion

Cohort 1 PARTA Treatment Group 1(Phase II); Cohort 1 PARTB(Phase II); Cohort 2 PARTA(Phase II); Cohort 2 PARTB(Phase II); Cohort 3(Phase II); Cohort 4(Phase II)

Penpulimab DRUG

IV infusion;200mg

Cohort 1 PARTA Treatment Group 2(Phase II)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures);
• ≥18 years old and ≤ 75 years (regardless of sex);
• ECOG performance status 0-1;
• Life expectancy longer than 3 months;
• )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;
• )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;
• Histologically or cytologically confirmed diagnosis of advanced colorectal adenocarcinoma with microsatellite stabilization;
• Measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1;
• Adequate organ function.

You may not qualify if:

• 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;
• 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;
• Participating in another clinical research;
• Has known active central nervous system (CNS) metastases, brain stem/meningeal metastasis, spinal cord metastasis or compression;
• Has an active autoimmune disease that has required systemic treatment in the past 2 years;
• 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;
• Past or currently has non-infectious pneumonia/interstitial lung disease that requires systemic glucocorticoid therapy;
• Has pleural effusion, pericardial effusion, or ascites that have clinical symptoms or require repeated drainage;
• Had a history of myocarditis, cardiomyopathy, and malignant arrhythmia;
• Has known allergy to any component of any investigational drug; a known history of severe hypersensitivity to other monoclonal antibodies;
• Pregnant or lactating female.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Liaoning Cancer Hospital

Shenyang, Liaoning, 110801, China

RECRUITING

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck

Interventions

Pemetrexed; Paclitaxel; Carboplatin; Docetaxel; Cisplatin; Fluorouracil; Cetuximab; Drug Therapy; penpulimab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Head and Neck Neoplasms; Neoplasms by Site

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Serum Globulins; Globulins; Therapeutics

Central Study Contacts

Wenting Li,M.D.

CONTACT

+86(0760)89873999; clinicaltrials@akesobio.com

Hongxu Liu,M.D.

CONTACT

Hongxuliu@qq.com

Study Design

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

Study Record Dates

• First Submitted: April 6, 2025
• First Posted: April 24, 2025
• Study Start: May 21, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2028
• Last Updated: June 3, 2025

Record last verified: 2025-05

Locations

CN (1)