Clinical trial NCT06594874: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Advanced Solid Tumors
Keywords: KRAS G12C
Non-Small Cell Lung Cancer
Metastatic Solid Tumor
Adebrelimab
Carboplatin
Pemetrexed
Cisplatin
Lead sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-09-19
Enrollment: 350
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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) .


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:

  1. Previous or current treatment with other KRAS G12C inhibitors
  2. 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.
  3. 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.
  4. 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

Primary outcomes:
measure: Number of Participants with Adverse Event(s) (AEs)
timeFrame: From Cycle 1 Day 1 to first documented progression of disease or death from any cause, approximately 2 years.
Secondary outcomes:
measure: Overall Response Rate (ORR)
timeFrame: From Cycle 1 Day 1 (C1D1) to disease progression or death, approximately 2 years.
measure: Disease Control Rate (DCR)
timeFrame: From C1D1 to disease progression or death, approximately 2 years.
measure: Time to Response (TTR)
timeFrame: Time from C1D1 until the date that measurement criteria for CR or PR (whichever is first recorded) are first met, approximately 2 years.
measure: Duration of Response (DOR)
timeFrame: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.
measure: Progression-Free Survival (PFS)
timeFrame: Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.
measure: Overall survival (OS)
timeFrame: C1D1 to date of death from any cause, approximately 5 years.
measure: Plasma Concentrations of HS-10370
timeFrame: C1D1 to date of death from any cause. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation, approximately 2 years.
measure: Maximum plasma concentration (Cmax)
timeFrame: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation.
measure: Time of maximum concentration (Tmax)
timeFrame: C1D1 to date of death from any cause, approximately 2 years. Various timepoints from Cycle 1 Day 1 through study treatment discontinuation
Other outcomes:
Locations:
city: Wuhan
country: China
facility: Union Hospital Tong Ji Medical College, HuaZhong University of Science and Technology
state: Hubei
Study officials:
References: