A Study of HS-10241 Combined With Almonertinib Versus Platinum-based Chemotherapy in Treatment of Advanced NSCLC With MET Amplification After Failure of EGFR-TKI Therapy

NCT06110663 | Unknown Phase 3

• 1 other identifier: HS-10241-301
• Study Type: interventional
• Target: 314
• Locations: 0 countries
• Sites: N/A

Brief Summary

HS-10241, an oral and highly selective MET-TKI, may contribute to overcoming common acquired MET-based resistance mechanisms following prior EGFR-TKI monotherapy. This study is conducted to evaluate the efficacy and safety of HS-10241 combined with Almonertinib versus platinum-based chemotherapy in NSCLC with MET amplification after failure of EGFR-TKI treatment.

Conditions

Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Progression-free Survival (PFS) evaluated by Independent Review Committee (IRC)

  Progression of tumor was assessed by RECIST 1.1 thereby to evaluate progression free survival. Progression-free survival was defined as the time from date of randomization until the documentation of objective disease progression (PD) or death from any cause in the absence of progression (whichever occurred first), regardless of whether they subsequently received non-study anti-cancer therapy.

  From the date of randomization to the earliest date of the first objective documentation of radiographic disease progression or death due to any cause, assessed up to 24 months

Secondary Outcomes (5)

• Objective response rate (ORR) evaluated by Independent Review Committee (IRC)

  From the date of randomization to disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.

• Disease control rate (DCR) evaluated by Independent Review Committee (IRC)

  From the date of randomization to disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.

• Duration of response (DoR) evaluated by Independent Review Committee (IRC)

  From the date of randomization to disease progression or date of death from any cause, whichever comes first, assessed up to 24 months.

• Overall survival (OS)

  From the date of randomization up to the date of date of death from any cause，assessed up to 24 months.

• Incidence and severity of treatment-emergent adverse events

  From the date of randomization until 28 days after the last dose

Study Arms (2)

HS-10241+Almonertinib

EXPERIMENTAL

Experimental group (Experimental): HS-10241 combined with Almonertinib NSCLC with MET amplification after failure of EGFR-TKI treatment randomized to HS-10241 combined with Almonertinib

Drug: HS-10241+ Almonertinib

Pemetrexed + Cisplatin /Carboplatin

ACTIVE COMPARATOR

Control group (Active Comparator): Pemetrexed combined with Platinum NSCLC with MET amplification after failure of EGFR-TKI treatment randomized to standard chemotherapy treatment of platinum-based chemotherapy

Drug: Pemetrexed + Cisplatin /Carboplatin

Interventions

HS-10241+ Almonertinib DRUG

HS-10241 300mg twice daily (BID) combined with Almonertinib 110mg once daily (QD) orally, for every cycle of 21 days until disease progression or other criteria for treatment discontinuation will be met.

HS-10241+Almonertinib

Pemetrexed + Cisplatin /Carboplatin DRUG

The standard chemotherapy treatment of cisplatin/carboplatin combined with pemetrexed for 4\~6 cycles (every 3 weeks). Participants will continue receive pemetrexed monotherapy until disease progression or other criteria for treatment discontinuation will be met.

Pemetrexed + Cisplatin /Carboplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men or women aged more than or equal to (≥) 18 years.
• Patients histologically or cytologically confirmed with locally advanced or metastatic NSCLC.
• Patients have previously received EGFR TKI treatment and had intolerance or disease progression by imaging recorded. Chemotherapy as systematic therapy is limited to no more than one prior line. Before randomization, all patients must provide imaging evidence of disease progression during or after the last treatment period. The patients are required to provide tumor biopsy tissue (required) and blood samples (optional) of disease progression after the last treatment of EGFR TKI, confirmed by central laboratory that there are EGFR sensitive mutations (deletion of exon 19 or L858R mutation) and T790M status (negative or positive) in tumor tissues and/or blood samples. Meanwhile, the tumor tissue should be c-MET positive confirmed by the central laboratory.
• According to Recist1.1, at least 1 target lesion that should be measurable lesions without local treatment like irradiation or with definite progression after local treatment and can be accurately measured at baseline as ≥ 10 mm in the longest diameter (except lymph nodes, which must have short axis ≥ 15mm)
• ECOG performance status of 0-1with no deterioration within 2 weeks before enrollment.
• Estimated life expectancy ≥three months.
• Females of child bearing age should adapt adequate contraceptive measures and should not be breastfeeding from the signing of informed consent to 6 months after the last treatment of the study. Male patients should be willing to use barrier contraception (i.e., condoms) from the signing of informed consent to 6 months after the last treatment of the study.
• Females must have a negative pregnancy test in 7 days prior to the date of randomization if of childbearing potential or must have evidence of non-childbearing potential by fulfilling any one of the criteria.
• Signed and dated Informed Consent Form.

You may not qualify if:

• Treatment with any of the following:
• Previous or current treatment with drugs targeting the c-MET/HGF pathway.
• Previous or under treatment with pemetrexed and platinum.
• Any cytotoxic chemotherapy, investigational agents, antitumor traditional Chinese Medicine and any other anticancer drugs for the treatment of advanced NSCLC within 14 days before the date of randomization; or requiring treatment with these drugs during the study.
• Any antitumor monoclonal antibody therapy within 28 days before the date of randomization.
• Local radiotherapy within 2 weeks of the date of randomization; receiving radiation to \> 30% of the bone marrow or with a wide field of radiation within 4 weeks before the date of randomization.
• Spinal cord compression or brain metastases (except for that being asymptomatic and stable for at least 4 weeks, not requiring steroids for at least 2 weeks prior to start of study treatment and with no obvious edema around the tumor focus by imaging examination).
• Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study.
• Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 with the exception of alopecia or neurotoxicity.
• History of other primary malignancies.
• Inadequate bone marrow reserve or organ function, as demonstrated by any of the following laboratory values:
• Absolute neutrophil count (ANC) \<1.5×109 / L
• Platelet count \<90×109 / L
• Hemoglobin \<90 g/L
• Total bilirubin (TBL) \> 1.5 × ULN or \> 3 × ULN in the presence of documented Gilbert's Syndrome (unconjugated hyperbilirubinemia) or liver metastases.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Pemetrexed; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 24, 2023
• First Posted: November 1, 2023
• Study Start: December 30, 2023
• Primary Completion: December 30, 2024
• Study Completion: February 28, 2025
• Last Updated: November 1, 2023

Record last verified: 2023-10