Study of HS-10241 in Combination With Almonertinib in Patients With Locally Advanced or Metastatic NSCLC

NCT05430386 | Unknown Phase 1

• 1 other identifier: HS-10241-102
• Study Type: interventional
• Target: 174
• Locations: 1 country
• Sites: 1

Brief Summary

This study is conducted to determine the safety, tolerability, pharmacokinetics and anti-tumor activity of HS-10241 when given together with Almonertinib in patients with EGFRm+ advanced NSCLC.

Conditions

Non Small Cell Lung Cancer

Keywords

NSCLC, c-Met,

Outcome Measures

Primary Outcomes (2)

• Part1-To determine the maximum tolerated dose (MTD)

  MTD was defined as the previous dose level at which 2 out of 3 patients or 2 out of 6 patients experienced a DLT.

  Up to day 28 from the first dose (4 weeks).

• Part2- Objective response rate (ORR )

  ORR was defined as the percentage of patients with a complete response (CR) or partial response (PR) that was confirmed at a subsequent scan at least 4 weeks later, as assessed according to RECIST version 1.1.

  From first dose until disease progression or withdrawal from study, assessed up to 24 months.

Secondary Outcomes (14)

• Incidence and severity of treatment-emergent adverse events

  From first dose until 28 days after the last dose

• Observed maximum plasma concentration (Cmax) after the first dose

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 first dose

• Observed maximum plasma concentration (C ss,max) after multiple dose

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of dosing in the second 28-Day cycle of therapy

• Observed minimum plasma concentration (C ss,min) after multiple dose

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 of dosing in the second 28-Day cycle of therapy

• Time to reach maximum plasma concentration (Tmax) after the first dose

  Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 first dose

Study Arms (1)

Dose escalation and dose expansion

EXPERIMENTAL

HS-10241 in combination with Almonertinib

Drug: HS-10241

Interventions

HS-10241 DRUG

Dose escalation: HS-10241 and Almonertinib will be administered in combination. Participants will continue treatment until the end of the study in the absence of unacceptable toxicities and confirmed disease progression. Dose expansion: HS-10241 and Almonertinib will be administered in the dose identified in Part 1 to further investigate the safety, tolerability, pharmacokinetics, and efficacy of this combination therapy.

Also known as: Almonertinib

Dose escalation and dose expansion

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.
• 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 start of first dose if of childbearing potential or must have evidence of non-childbearing potential by fulfilling any one of the following criteria:
• Postmenopausal defined as age more than 60 years and amenorrheic for at least 12 months following cessation of all exogenous hormonal treatments.
• Women under 60 years old would be considered postmenopausal if they have been amenorrheic for 12 months or more, following cessation of exogenous hormonal treatments, and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels in the postmenopausal range for the laboratory.
• Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy, or bilateral salpingectomy, but not by tubal ligation.
• Part2 Cohort 1 -Patients have previously received the 1st/2nd/3rd-generation EGFR TKI (only one kind of them) and had disease progression by imaging recorded with centrally confirmed EGFR mutation, T790M negative and MET-positive.
• Cohort2- Patients have not received any systemic treatment of advanced NSCLC with centrally confirmed EGFR mutation and MET-positive.
• Cohort3- Patients have previously received both 1st/2nd and 3rd-generation EGFR-TKI and had disease progression by imaging recorded with centrally confirmed EGFR mutation and MET-positive.
• Cohort4-Patients have previously received the 1st/2nd-generation EGFR TKI continuous treatment (not received the 3rd-generation EGFR TKI treatment) and had disease progression by imaging recorded with centrally confirmed EGFR mutation, T790M positive and MET-positive.
• \*Definition of MET-positive (any one of the following): ① Fluorescence in situ hybridization (FISH): MET gene copy number ≥ 5 or MET/CEP7 ratio ≥ 2; ② Immunohistochemistry (IHC): ≥ 50% tumor cells MET 3+.

You may not qualify if:

• Treatment with any of the following:
• Previous or current treatment with drugs targeting the c-MET/HGF pathway.
• 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 first dose of study drug; or requiring treatment with these drugs during the study.
• Any antitumor monoclonal antibody therapy within 28 days before the first dose of study drug.
• Local radiotherapy within 2 weeks of the first dose of study drug; receiving radiation to \> 30% of the bone marrow or with a wide field of radiation within 4 weeks before the first dose of study drug.
• Pleural or peritoneal effusion requiring clinical intervention (except for effusion not requiring drainage or being stable after drainage for at least 14 days before the first dose of study drug). Pericardial effusion (except for effusion being stable after drainage for at least 14 days before the first dose of study drug).
• Major surgery within 4 weeks of the first dose of study drug.
• 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).
• Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study.
• Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study.
• Currently receiving or requiring long-term treatment with warfarin (LMWH is allowed).
• 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, excluding:
• Non-melanoma skin cancer or malignant freckle mole with adequate treatment and no evidence of disease recurrence.
• Carcinoma in situ with adequate treatment and no evidence of disease recurrence.

Sponsors & Collaborators

• Jiangsu Hansoh Pharmaceutical Co., Ltd.: lead

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200032, China

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

aumolertinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Shun Lu, MD

  Shanghai Chest Hospital

  PRINCIPAL INVESTIGATOR

• Jiahua Chen, MD

  Hunan Cancer Hospital

  PRINCIPAL INVESTIGATOR

• Xiaorong Dong, MD

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

• Ying Cheng, MD

  Jilin Provincial Tumor Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shun Lu, MD

CONTACT

86-21-22200000; shun_lu@hotmail.com

Zhonglin Chen, MD

CONTACT

86-21-22200000; chestgcp@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 14, 2022
• First Posted: June 24, 2022
• Study Start: January 5, 2022
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2023
• Last Updated: February 14, 2023

Record last verified: 2023-02

Locations

CN (1)