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

NCT ID: NCT06594874

Last Updated: 2024-09-19

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE1
• Total Enrollment: 350 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-10-31
• Study Completion Date: 2027-01-01

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) .

Conditions

Non-Small Cell Lung Cancer; Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm A: HS-10370 dose 1 + Adebrelimab

Participants will receive HS-10370 dose 1 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Group Type: EXPERIMENTAL

HS-10370

Intervention Type: DRUG

HS-10370 administered orally every day

Adebrelimab

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Arm B: HS-10370 dose 2 + Adebrelimab

Participants will receive HS-10370 dose 2 administered orally plus Adebrelimab given as a 20 mg/kg intravenous infusion(IV) once every 21-day cycle up to a total of 35 cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Group Type: EXPERIMENTAL

HS-10370

Intervention Type: DRUG

HS-10370 administered orally every day

Adebrelimab

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Arm C: HS-10370+ Adebrelimab + Pemetrexed and Platinum

Participants will receive HS-10370 administered orally in plus with Adebrelimab, pemetrexed, and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met

Group Type: EXPERIMENTAL

HS-10370

Intervention Type: DRUG

HS-10370 administered orally every day

Adebrelimab

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Cisplatin

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Carboplatin

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Pemetrexed

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Arm D: HS-10370+ Adebrelimab + Pemetrexed

Participants will receive HS-10370 administered orally in plus with Adebrelimab and pemetrexed administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Group Type: EXPERIMENTAL

HS-10370

Intervention Type: DRUG

HS-10370 administered orally every day

Adebrelimab

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Pemetrexed

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Arm E: HS-10370+ Pemetrexed and Platinum

Participants will receive HS-10370 administered orally in plus with pemetrexed and platinum (cisplatin or carboplatin) administered IV in 21-day cycles. Participants may continue to receive treatment until discontinuation criteria are met.

Group Type: EXPERIMENTAL

HS-10370

Intervention Type: DRUG

HS-10370 administered orally every day

Cisplatin

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Carboplatin

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Pemetrexed

Intervention Type: DRUG

Administered intravenously every 21 days; dose by label.

Interventions

HS-10370

HS-10370 administered orally every day

Intervention Type: DRUG

Adebrelimab

Administered intravenously every 21 days; dose by label.

Intervention Type: DRUG

Cisplatin

Administered intravenously every 21 days; dose by label.

Intervention Type: DRUG

Carboplatin

Administered intravenously every 21 days; dose by label.

Intervention Type: DRUG

Pemetrexed

Administered intravenously every 21 days; dose by label.

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Jiangsu Hansoh Pharmaceutical Co., Ltd.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

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

Wuhan, Hubei, China

Countries

China

Central Contacts

Xiaorong Dong, PhD

Role: CONTACT

xhzzdxr@126.com

13986252286

Other Identifiers

HS-10370-102

Identifier Type: -

Identifier Source: org_study_id