A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Patients With Advanced Solid Tumors

Official title

A Phase Ib Study Evaluating the Safety, Tolerability , Pharmacokinetics，Activity and Immunogenicity of HS-10370 in Addition to Other Anti-cancer Therapies in Patients With Advanced Solid Tumors

Overview

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

• Drug HS-10370
  Participants will receive HS-10370 dose 1 administered orally
• Drug HS-20117
  Participants will receive HS-20117 given as dose 3 intravenous infusion(IV) once every 14-day cycle.
• Drug Adebrelimab
  Participants will receive Adebrelimab intravenous infusion(IV) once every 21-day cycle
• Drug Capecitabine
  Participants will receive Capecitabine administered orally
• Drug Oxaliplatin
  Participants will receive Oxaliplatin intravenous infusion(IV) once every 21-day cycle.
• Drug Folinic Acid, Fluorouracil and Oxaliplatin/Irinotecan
  Participants will receive Folinic Acid, Fluorouracil and Oxaliplatin/Irinotecan intravenous infusion(IV) once every 14-day cycle.
• Drug HS-20093
  Participants will receive HS-20093 intravenous infusion(IV) once every 21-day cycle
• Drug platinum (cisplatin or carboplatin)
  Participants will receive platinum (cisplatin or carboplatin) administered IV in 21-day cycles.

Primary outcome measures

• Number of Participants with Adverse Event(s) (AEs) [Time frame: From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days).]

Secondary outcome measures (9)

• Overall Response Rate (ORR) [Time frame: From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days).]
• Disease Control Rate (DCR) [Time frame: From Cycle 1 Day 1 (C1D1) to disease progression or death, up to 2 years (each cycle is 14 days).]
• Time to Response (TTR) [Time frame: 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).]
• Duration of Response (DOR) [Time frame: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years]
• Progression-Free Survival (PFS) [Time frame: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years]
• Overall survival (OS) [Time frame: Cycle 1 Day 1 to date of death from any cause, up to 5 years (each cycle is 14 days)]
• Plasma Concentrations of HS-10370 [Time frame: 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)]
• Maximum plasma concentration (Cmax) [Time frame: 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)]
• Time of maximum concentration (Tmax) [Time frame: 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)]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 2 centers

• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hangzhou
• Sun Yat-sen University Cancer Center — Shanghai

Identifiers

NCT: NCT06963502 · HS-10370-103

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗