A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Patients With Advanced Solid Tumors
- Conditions
- Advanced Solid TumorsColorectal CancerNon-Small Cell Lung Cancer
- Interventions
- Drug: Folinic Acid, Fluorouracil and Oxaliplatin/Irinotecan
- Registration Number
- NCT06963502
- Lead Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 762
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1:HS-10370 dose 1+ HS-20117 dose 3 HS-10370 - Arm 1:HS-10370 dose 1+ HS-20117 dose 3 HS-20117 - Arm 2: HS-10370 dose 2 +HS-20117 dose 4+ Adebrelimab HS-10370 - Arm 2: HS-10370 dose 2 +HS-20117 dose 4+ Adebrelimab HS-20117 - Arm 2: HS-10370 dose 2 +HS-20117 dose 4+ Adebrelimab Adebrelimab - Arm 3: HS-10370 dose 1 + HS-20117 dose4 + Chemotherapy HS-10370 - Arm 3: HS-10370 dose 1 + HS-20117 dose4 + Chemotherapy Capecitabine - Arm 3: HS-10370 dose 1 + HS-20117 dose4 + Chemotherapy Oxaliplatin - Arm 3: HS-10370 dose 1 + HS-20117 dose4 + Chemotherapy HS-20117 - Arm 5:HS-10370 dose1+ HS-20117 dose 4+HS-20093 dose 5 HS-10370 - Arm 5:HS-10370 dose1+ HS-20117 dose 4+HS-20093 dose 5 HS-20117 - Arm 5:HS-10370 dose1+ HS-20117 dose 4+HS-20093 dose 5 HS-20093 - Arm 6:HS-10370 dose 2 +HS-20093 dose 5+ Adebrelimab HS-10370 - Arm 4: HS-10370 dose 1 + HS-20117 dose3 + Chemotherapy HS-10370 - Arm 4: HS-10370 dose 1 + HS-20117 dose3 + Chemotherapy HS-20117 - Arm 4: HS-10370 dose 1 + HS-20117 dose3 + Chemotherapy Folinic Acid, Fluorouracil and Oxaliplatin/Irinotecan - Arm 6:HS-10370 dose 2 +HS-20093 dose 5+ Adebrelimab Adebrelimab - Arm 6:HS-10370 dose 2 +HS-20093 dose 5+ Adebrelimab HS-20093 - Arm 7:HS-10370 dose 2 +HS-20093 dose 6+ Adebrelimab+ Chemotherapy HS-10370 - Arm 7:HS-10370 dose 2 +HS-20093 dose 6+ Adebrelimab+ Chemotherapy Adebrelimab - Arm 7:HS-10370 dose 2 +HS-20093 dose 6+ Adebrelimab+ Chemotherapy HS-20093 - Arm 7:HS-10370 dose 2 +HS-20093 dose 6+ Adebrelimab+ Chemotherapy platinum (cisplatin or carboplatin) -
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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
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
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
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.
Trial Locations
- Locations (2)
The Second Affiliated Hospital of Zhejiang University School of Medicine
🇨🇳Hangzhou, China
Sun Yat-sen University Cancer Center
🇨🇳Shanghai, China