Non-small Cell Lung Cancer Stage IIIB/IV, Head and Neck Squamous Cell Carcinoma (HNSCC), Colorectal Adenocarcinoma, Advanced Solid Tumors
Conditions
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.
Interventions
DRUGPemetrexed
IV infusion;500mg/m2
DRUGPaclitaxel
IV infusion;175mg/m2
DRUGAK129(dose 1)
IV infusion
DRUGCarboplatin
IV infusion;AUC 5
DRUGAK129(dose 2)
IV infusion
DRUGDocetaxel
IV infusion;75mg/m2
DRUGCis-platinum
IV infusion;100 mg/m2
IV infusion;1000 mg/m2
DRUGCetuximab
IV infusion;400mg/m2/ 250mg/m2
DRUGChemotherapy
IV infusion
DRUGAK129(RP2D)
IV infusion
DRUGPenpulimab
IV infusion;200mg
Sponsors
Akeso
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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 |
| Time to Response (TTR) | Up to approximately 2 years | Evaluation of TTR based on RECIST v1.1. |
| Progression-Free Survival (PFS) | Up to approximately 2 years | Evaluation of PFS based on RECIST v1.1. |
Countries
China
Contacts
Primary ContactWenting Li,M.D.
Backup ContactHongxu Liu,M.D.
Outcome results
None listed