A Phase Ib Study of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors

Official title

A Phase Ib Study Evaluating the Safety, Tolerability , Pharmacokinetics and Activity of HS-10370 in Addition to Other Anti-cancer Therapies in Participants with KRAS G12C Mutation Advanced Solid Tumors

Overview

This is a Phase Ib study that will evaluate the Safety, Tolerability , Pharmacokinetics and Activity of HS-10370 in Combination With Other Anti-cancer Therapies in patients with KRAS G12C mutation advanced or metastatic solid tumors, especially in non-Small cell lung cancer (NSCLC) .

Interventions

• Drug HS-10370
  HS-10370 administered orally every day
• Drug Adebrelimab
  Administered intravenously every 21 days; dose by label.
• Drug Cisplatin
  Administered intravenously every 21 days; dose by label.
• Drug Carboplatin
  Administered intravenously every 21 days; dose by label.
• Drug Pemetrexed
  Administered intravenously every 21 days; dose by label.

Primary outcome measures

• Number of Participants with Adverse Event(s) (AEs) [Time frame: From Cycle 1 Day 1 to first documented progression of disease or death from any cause, approximately 2 years.]

Secondary outcome measures (9)

• Overall Response Rate (ORR) [Time frame: From Cycle 1 Day 1 (C1D1) to disease progression or death, approximately 2 years.]
• Disease Control Rate (DCR) [Time frame: From C1D1 to disease progression or death, approximately 2 years.]
• Time to Response (TTR) [Time frame: Time from C1D1 until the date that measurement criteria for CR or PR (whichever is first recorded) are first met, approximately 2 years.]
• 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: C1D1 to date of death from any cause, approximately 5 years.]
• Plasma Concentrations of HS-10370 [Time frame: C1D1 to date of death from any cause. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation, approximately 2 years.]
• Maximum plasma concentration (Cmax) [Time frame: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation.]
• Time of maximum concentration (Tmax) [Time frame: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation]

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.
• Histologically or cytologically confirmed NSCLC with Stage IIIB-IIIC or Stage IV disease, not suitable for curative intent radical surgery or radiation therapy.
• Documentation of the presence of a KRAS G12C mutation
• Must provide tumor tissue sample
• No history of systemic anticancer therapy in metastatic/non-curable settings
• 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.
• Females must have the evidence of non-childbearing potential; Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Signed and dated Informed Consent Form.
• 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
• Any cytotoxic chemotherapy, anticancer Chinese medicine and targeted small molecule inhibitors within 14 days of the first dose of study treatment; Any investigational agents and large molecule antibodies within 28 days of the first dose of study treatment.
• Local radiotherapy within 2 weeks prior to the first dose of study drug, more than 30% of bone marrow irradiation or large-area radiotherapy within 4 weeks before the first dose of study drug.
• Major surgery (including craniotomy, thoracotomy, or laparotomy, etc.) within 4 weeks of the first dose
• 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 · 1 center

• Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology — Wuhan

Identifiers

NCT: NCT06594874 · HS-10370-102

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗