AK129 Combination Therapy for Advanced Solid Tumors

Akeso

Status and phase

Not yet enrolling

Phase 2

Phase 1

Conditions

Colorectal Adenocarcinoma

Advanced Solid Tumors

Non-small Cell Lung Cancer Stage IIIB/IV

Head and Neck Squamous Cell Carcinoma (HNSCC)

Treatments

Drug: Docetaxel

Drug: 5-FU (5-fluorouracil)

Drug: Chemotherapy

Drug: AK129(dose 1)

Drug: AK129(RP2D)

Drug: AK129(dose 2)

Drug: Penpulimab

Drug: Pemetrexed

Drug: Carboplatin

Drug: Cetuximab

Drug: Cis-platinum

Drug: Paclitaxel

Study type

Interventional

Funder types

Industry

Identifiers

NCT06943820

AK129-201

Details and patient eligibility

About

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.

Enrollment

230 estimated patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

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;
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;
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;
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.

Exclusion criteria

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.

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

230 participants in 9 patient groups

AK129(dose 1) + Chemotherapy(Phase Ib)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pemetrexed

Drug: AK129(dose 1)

AK129(dose 2) + Chemotherapy(Phase Ib)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pemetrexed

Drug: AK129(dose 2)

Cohort 1 PARTA Treatment Group 1(Phase II)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pemetrexed

Drug: AK129(RP2D)

Cohort 1 PARTA Treatment Group 2(Phase II)

Active Comparator group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Carboplatin

Drug: Pemetrexed

Drug: Penpulimab

Cohort 1 PARTB(Phase II)

Experimental group

Description:

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

Treatment:

Drug: AK129(RP2D)

Drug: Docetaxel

Cohort 2 PARTA(Phase II)

Experimental group

Description:

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.

Treatment:

Drug: Cis-platinum

Drug: Carboplatin

Drug: AK129(RP2D)

Drug: 5-FU (5-fluorouracil)

Cohort 2 PARTB(Phase II)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: Cetuximab

Drug: AK129(RP2D)

Drug: Docetaxel

Cohort 3(Phase II)

Experimental group

Description:

CRC:Subjects receive AK129(RP2D) until progression.

Treatment:

Drug: AK129(RP2D)

Cohort 4(Phase II)