AK129 Combination Therapy for Advanced Solid Tumors

May 28, 2025 updated by: Akeso

A Phase Ib/II Study of Anti-PD-1/LAG-3 Bispecific Antibody AK129 Combinations in Advanced Solid Tumors

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

230

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
    • Liaoning
      • Shenyang, Liaoning, China, 110801
        • Recruiting
        • Liaoning Cancer Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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.
Drug: AK129(dose 1)
IV infusion
Drug: Pemetrexed
IV infusion;500mg/m2
Drug: Paclitaxel
IV infusion;175mg/m2
Drug: Carboplatin
IV infusion;AUC 5
Drug: Paclitaxel
IV infusion;80mg/m2
Experimental: 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.
Drug: Pemetrexed
IV infusion;500mg/m2
Drug: Paclitaxel
IV infusion;175mg/m2
Drug: Carboplatin
IV infusion;AUC 5
Drug: Paclitaxel
IV infusion;80mg/m2
Drug: AK129(dose 2)
IV infusion
Experimental: 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.
Drug: Pemetrexed
IV infusion;500mg/m2
Drug: Paclitaxel
IV infusion;175mg/m2
Drug: Carboplatin
IV infusion;AUC 5
Drug: Paclitaxel
IV infusion;80mg/m2
Drug: AK129(RP2D)
IV infusion
Active Comparator: 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.
Drug: Pemetrexed
IV infusion;500mg/m2
Drug: Paclitaxel
IV infusion;175mg/m2
Drug: Carboplatin
IV infusion;AUC 5
Drug: Paclitaxel
IV infusion;80mg/m2
Drug: Penpulimab
IV infusion;200mg
Experimental: Cohort 1 PARTB(Phase II)
NSCLC:Subjects receive AK129(RP2D) plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.
Drug: AK129(RP2D)
IV infusion
Drug: Docetaxel
IV infusion;75mg/m2
Drug: Docetaxel
IV infusion;35mg/m2
Experimental: 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.
Drug: Carboplatin
IV infusion;AUC 5
Drug: AK129(RP2D)
IV infusion
Drug: Cis-platinum
IV infusion;100 mg/m2
Drug: 5-FU (5-fluorouracil)
IV infusion;1000 mg/m2
Experimental: 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.
Drug: Paclitaxel
IV infusion;175mg/m2
Drug: Paclitaxel
IV infusion;80mg/m2
Drug: AK129(RP2D)
IV infusion
Drug: Docetaxel
IV infusion;75mg/m2
Drug: Docetaxel
IV infusion;35mg/m2
Drug: Cetuximab
IV infusion;400mg/m2/ 250mg/m2
Experimental: Cohort 3(Phase II)
CRC:Subjects receive AK129(RP2D) until progression.
Drug: AK129(RP2D)
IV infusion
Experimental: Cohort 4(Phase II)
Advanced solid tumors:Subjects receive AK129(RP2D)± chemotherapy until progression.
Drug: AK129(RP2D)
IV infusion
Drug: Chemotherapy
IV infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Frequency and severity of adverse events (AEs) ,Clinically significant abnormal laboratory results
Time Frame: Up to approximately 2 years
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)
Time Frame: 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.
Up to approximately 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Anti-Drug Antibodies(ADAs)
Time Frame: Up to approximately 2 years
Number and percentage of patients with detectable anti-drug antibodies
Up to approximately 2 years
Progression-Free Survival (PFS)
Time Frame: Up to approximately 2 years
Evaluation of PFS based on RECIST v1.1.
Up to approximately 2 years
Overall survival (OS)
Time Frame: Up to approximately 2 years
Evaluation of OS based on RECIST v1.1.
Up to approximately 2 years
Disease control rate (DCR)
Time Frame: Up to approximately 2 years
Evaluation of DCR based on RECIST v1.1.
Up to approximately 2 years
Duration of Response (DoR)
Time Frame: Up to approximately 2 years
Evaluation of DoR based on RECIST v1.1.
Up to approximately 2 years
Time to Response (TTR)
Time Frame: Up to approximately 2 years
Evaluation of TTR based on RECIST v1.1.
Up to approximately 2 years
Overall Response Rate (ORR)
Time Frame: 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.
Up to approximately 2 years
Pharmacokinetics (PK)
Time Frame: Up to cycle 21(each cycle is 21 days)
PK parameters: serum concentrations of AK129 at different point of time
Up to cycle 21(each cycle is 21 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Akeso

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 21, 2025

Primary Completion (Estimated)

December 1, 2026

Study Completion (Estimated)

May 1, 2028

Study Registration Dates

First Submitted

April 6, 2025

First Submitted That Met QC Criteria

April 17, 2025

First Posted (Actual)

April 24, 2025

Study Record Updates

Last Update Posted (Actual)

June 3, 2025

Last Update Submitted That Met QC Criteria

May 28, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AK129-201

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Advanced Solid Tumors

Clinical Trials on AK129(dose 1)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Pakistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe