NCT06594874

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) .

Trial Health

63
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Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
350

participants targeted

Target at P75+ for phase_1 nonsmall-cell-lung-cancer

Timeline
8mo left

Started Oct 2024

Shorter than P25 for phase_1 nonsmall-cell-lung-cancer

Geographic Reach
1 country

1 active site

Status
not yet recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress70%
Oct 2024Jan 2027

First Submitted

Initial submission to the registry

September 4, 2024

Completed
15 days until next milestone

First Posted

Study publicly available on registry

September 19, 2024

Completed
1 month until next milestone

Study Start

First participant enrolled

October 31, 2024

Completed
2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 31, 2026

Expected
2 months until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2027

Last Updated

September 19, 2024

Status Verified

September 1, 2024

Enrollment Period

2 years

First QC Date

September 4, 2024

Last Update Submit

September 10, 2024

Conditions

Keywords

KRAS G12CNon-Small Cell Lung CancerMetastatic Solid TumorAdebrelimabCarboplatinPemetrexedCisplatin

Outcome Measures

Primary Outcomes (1)

  • Number of Participants with Adverse Event(s) (AEs)

    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)

    From Cycle 1 Day 1 to first documented progression of disease or death from any cause, approximately 2 years.

Secondary Outcomes (9)

  • Overall Response Rate (ORR)

    From Cycle 1 Day 1 (C1D1) to disease progression or death, approximately 2 years.

  • Disease Control Rate (DCR)

    From C1D1 to disease progression or death, approximately 2 years.

  • Time to Response (TTR)

    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)

    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)

    Date of first evidence of CR or PR to date of disease progression or death from any cause, approximately 2 years.

  • +4 more secondary outcomes

Study Arms (5)

Arm A: HS-10370 dose 1 + Adebrelimab

EXPERIMENTAL

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.

Drug: HS-10370Drug: Adebrelimab

Arm B: HS-10370 dose 2 + Adebrelimab

EXPERIMENTAL

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.

Drug: HS-10370Drug: Adebrelimab

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

EXPERIMENTAL

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

Drug: HS-10370Drug: AdebrelimabDrug: CisplatinDrug: CarboplatinDrug: Pemetrexed

Arm D: HS-10370+ Adebrelimab + Pemetrexed

EXPERIMENTAL

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.

Drug: HS-10370Drug: AdebrelimabDrug: Pemetrexed

Arm E: HS-10370+ Pemetrexed and Platinum

EXPERIMENTAL

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.

Drug: HS-10370Drug: CisplatinDrug: CarboplatinDrug: Pemetrexed

Interventions

HS-10370 administered orally every day

Arm A: HS-10370 dose 1 + AdebrelimabArm B: HS-10370 dose 2 + AdebrelimabArm C: HS-10370+ Adebrelimab + Pemetrexed and PlatinumArm D: HS-10370+ Adebrelimab + PemetrexedArm E: HS-10370+ Pemetrexed and Platinum

Administered intravenously every 21 days; dose by label.

Arm A: HS-10370 dose 1 + AdebrelimabArm B: HS-10370 dose 2 + AdebrelimabArm C: HS-10370+ Adebrelimab + Pemetrexed and PlatinumArm D: HS-10370+ Adebrelimab + Pemetrexed

Administered intravenously every 21 days; dose by label.

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

Administered intravenously every 21 days; dose by label.

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

Administered intravenously every 21 days; dose by label.

Arm C: HS-10370+ Adebrelimab + Pemetrexed and PlatinumArm D: HS-10370+ Adebrelimab + PemetrexedArm E: HS-10370+ Pemetrexed and Platinum

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • +11 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

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

Wuhan, Hubei, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell LungNeoplasm Metastasis

Interventions

CisplatinCarboplatinPemetrexed

Condition Hierarchy (Ancestors)

Carcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsNeoplasms by SiteNeoplasmsLung DiseasesRespiratory Tract DiseasesNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsCoordination ComplexesOrganic ChemicalsGuanineHypoxanthinesPurinonesPurinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsGlutamatesAmino Acids, AcidicAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Dicarboxylic

Central Study Contacts

Xiaorong Dong, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

September 4, 2024

First Posted

September 19, 2024

Study Start

October 31, 2024

Primary Completion (Estimated)

October 31, 2026

Study Completion (Estimated)

January 1, 2027

Last Updated

September 19, 2024

Record last verified: 2024-09

Locations