Advanced Non-Small Cell Lung Cancer
Conditions
Brief summary
This Phase Ib/III study evaluates the efficacy and safety of IBI351 in combination with chemotherapy in advanced non-squamous NSCLC with KRAS G12C mutation.
Detailed description
This Phase Ib/III study evaluates the efficacy and safety of IBI351 in combination with chemotherapy. There will be five cohorts of subjects, all of whom have KRAS G12C mutation and have advanced or metastatic NSCLC. Those five cohorts (A, B,C ,D and E) are treated with IBI351, IBI351+Sintilimab,IBI351+pemetrexed+cis-platinum/carboplatin,IBI351+Cetuximab, or IBI351+pemetrexed+cis-platinum/carboplatin respectively. IBI351 is an orally available small molecule inhibitor of KRAS G12C.
Interventions
DRUGIBI351
recommended dose, po
DRUGCetuximab
500mg/m\^2, Q2W, day1, i.v.
DRUGpemetrexed
500mg/m\^2, Q3W, day1, i.v.
DRUGCarboplatin
AUC=5, Q3W, day1, i.v.
DRUGSintilimab
200mg, Q3W, day1, i.v.
DRUGcis-platinum
75mg/m\^2, Q3W, day1, i.v.
Sponsors
Innovent Biologics (Suzhou) Co. Ltd.
Study design
Allocation
NON_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. Histologically confirmed diagnosis of nonsquamous NSCLC with KRAS G12C mutation 2. Unresectable or metastatic disease 3. Adequate organ function 4. Not received any systemic antitumor therapy for locally advanced or metastatic non-squamous NSCLC previously.
Exclusion criteria
1. History of intestinal disease or major gastric surgery or inability to swallow oral medications 2. Prior therapy with agents targeting KRAS G12C mutation (e.g., AMG 510). 3. Active brain metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with dose limiting toxicity | 12 months | Number of participants with dose limiting toxicity in the dose escalation period |
| Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents | 24 months | Objective response rate per RECIST v1.1 |
| Safety indicators during the introduction phase for IBI351 combination treatment : | 24 months | Number of participants with Adverse events (AE), Treatment Emergent Adverse events (TEAE), treatment-related Adverse events (TEAE), TRAE) and the incidence of Serious Adverse events (SAE) (CTCAE v5.0 standard), with abnormal vital signs, abnormal physical exams, abnormal laboratory results and abnormal 12-lead electrocardiogram |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate clearance of IBI351 from the plasma | 12 months | CL/F |
| Evaluate distribution of IBI351 | 12 months | V/F |
| Evaluate clinical efficacy of IBI351 in combination with other therapeutic agents with other index | 24 months | PFS, DCR,DOR, TTR per RECIST v1.1; OS |
| Number of subjects with adverse events of interest | 24 months | AE |
| Evaluate plasma peak concentration of IBI351 | 12 months | Cmax |
| Number of subjects with serious adverse events | 24 months | SAE |
| Number of subjects with treatment-emergent adverse events | 24 months | TEAE |
| Overall Survival | 24 months | OS |
| Number of subjects with treatment-related adverse events | 24 months | TRAE |
| Evaluate area under the plasma concentration-time curve (AUC) of IBI351 | 12 months | AUC |
| Evaluate terminal half-life (t1/2) of IBI351 | 12 months | t1/2 |
Countries
China
Contacts
Primary ContactHaiyan Zhu
Outcome results
None listed