Advanced Solid Tumors, Colorectal Cancer, Non-Small Cell Lung Cancer
Conditions
Brief summary
This is a Phase Ib study that will evaluate the Safety, Tolerability , Pharmacokinetics, Activity and Immunogenicity of HS-10370 in Combination With Other Anti-cancer Therapies in Chinese patients with KRAS G12C mutation advanced or metastatic solid tumors, especially in and Colorectal cancer(CRC) and non-Small cell lung cancer (NSCLC).
Interventions
DRUGHS-10370
Participants will receive HS-10370 dose 1 administered orally
DRUGHS-20117
Participants will receive HS-20117 given as dose 3 intravenous infusion(IV) once every 14-day cycle.
DRUGAdebrelimab
Participants will receive Adebrelimab intravenous infusion(IV) once every 21-day cycle
DRUGCapecitabine
Participants will receive Capecitabine administered orally
DRUGOxaliplatin
Participants will receive Oxaliplatin intravenous infusion(IV) once every 21-day cycle.
DRUGFolinic Acid, Fluorouracil and Oxaliplatin/Irinotecan
Participants will receive Folinic Acid, Fluorouracil and Oxaliplatin/Irinotecan intravenous infusion(IV) once every 14-day cycle.
DRUGHS-20093
Participants will receive HS-20093 intravenous infusion(IV) once every 21-day cycle
Participants will receive platinum (cisplatin or carboplatin) administered IV in 21-day cycles.
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Men or women greater than or equal to 18 years * At least one measurable lesion in accordance with RECIST 1.1 * Must have an ECOG performance status of 0 or 1. * Patients with advanced solid tumors who have failed after adequate standard treatment, are intolerant to standard treatment, or have no standard treatment available. * Documentation of the presence of a KRAS G12C mutation * Estimated life expectancy ≥12 weeks. * Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 6 months after the last dose.Men also consent to use adequate contraceptive method within the same time limit. * The subjects are able to comply with the process of the protocol.
Exclusion criteria
* Treatment with any of the following: Previous or current treatment with other KRAS G12C inhibitors. * Active brain metastases. * Patients with uncontrolled pleural, ascites or pericardial effusion * Spinal cord compression * Presence of Grade ≥ 2 toxicities due to prior anti-tumor therapy. * Subjects with tumors known to harbor molecular alterations for which targeted therapy is locally approved, except for KRAS G12C. * History of other primary malignancies. * Inadequate bone marrow reserve or organ functions. * Abnormal cardiac examination results. * Severe, uncontrolled or active cardiovascular disorders. * Diabetes ketoacidosis or hyperglycemia hyperosmolality * Uncontrolled hypertension. * Severe bleeding symptoms or bleeding tendencies. * Severe arteriovenous thrombosis occurred * Serious infection. * Continuous use of glucocorticoids * Active infectious diseases. * Refractory nausea, vomiting, or chronic gastrointestinal diseases, or inability to swallow oral medications * Hepatic encephalopathy, hepatorenal syndrome, or ≥ Child Pugh B-grade cirrhosis. * Interstitial lung disease (ILD). * Serious neurological or mental disorders. * Active autoimmune diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Adverse Event(s) (AEs) | From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days). | An adverse event (AE) is defined as any untoward medical occurrence in a patient and which does not necessarily have a causal relationship with this treatment. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days). | Percentage of Participants who Achieve a Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR).ORR by the Investigator According to RECIST v1.1 |
| Time to Response (TTR) | Time from Cycle 1 Day 1 until the date that measurement criteria for CR or PR (whichever is first recorded) are first met, up to 2 years (each cycle is 14 days). | TTR by the Investigator According to RECIST v1.1 |
| Duration of Response (DOR) | Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years | DOR by the Investigator According to RECIST v1.1 |
| Progression-Free Survival (PFS) | Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years | PFS by the Investigator According to RECIST v1.1 |
| Disease Control Rate (DCR) | From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days). | Percentage of Participants who Achieve a BOR of CR, PR, or Stable Disease (SD).DCR by the Investigator According to RECIST v1.1 |
| Plasma Concentrations of HS-10370 | Cycle 1 Day 1 to date of death from any cause. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation, up to 2 years. (each cycle is 14 days) | Defined as the time from C1D1 to death from any cause |
| Maximum plasma concentration (Cmax) | Cycle 1 Day 1 to date of death from any cause, up to 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (each cycle is 14 days) | Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. |
| Time of maximum concentration (Tmax) | Cycle 1 Day 1 to date of death from any cause, up to 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (each cycle is 14 days) | Tmax is defined as the time required for a drug to reach peak concentration in plasma. |
| Overall survival (OS) | Cycle 1 Day 1 to date of death from any cause, up to 5 years (each cycle is 14 days) | Defined as the time from C1D1 to death from any cause by the Investigator According to RECIST v1.1 |
Countries
China
Outcome results
None listed