A Phase Ib Study to Assess the Safety, Tolerability, Pharmacokinetics and Efficacy of HS-10241 in Combination With Almonertinib in Patients With Locally Advanced or Metastatic NSCLC.
Overview
- Phase
- Phase 1
- Intervention
- HS-10241
- Conditions
- Non Small Cell Lung Cancer
- Sponsor
- Jiangsu Hansoh Pharmaceutical Co., Ltd.
- Enrollment
- 174
- Locations
- 1
- Primary Endpoint
- Part1-To determine the maximum tolerated dose (MTD)
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
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.
Detailed Description
This is a phase Ⅰb, multicenter study to evaluate safety, tolerability, pharmacokinetics, and efficacy of HS-10241 administered orally in combination with Almonertinib in patients with EGFRm+ locally advanced or metastatic NSCLC who have progressed following prior EGFR-TKI therapy. The study consist of two parts: Part 1 is the dose escalation period to observe the safety, tolerance, PK characteristics and preliminary anti-tumor activity, and determine the maximum tolerated dose (MTD) or maximum applicable dose (MAD) of combined administration; Part 2 is the dose expansion period to select appropriate doses in different target populations and further evaluate the efficacy, safety, tolerance and PK characteristics of combined administration, and determine the phase II recommended dose (RP2D). All patients will be carefully followed for adverse events during the study treatment and for 28 days after the last dose of study drug. Patients of this study will be permitted to continue therapy with assessments for progression once every 8 weeks, if the product is well tolerated and the subject has stable disease or better. Survival follow-up is recommended once every 12 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •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.
Exclusion Criteria
- •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.
Arms & Interventions
Dose escalation and dose expansion
HS-10241 in combination with Almonertinib
Intervention: HS-10241
Outcomes
Primary Outcomes
Part1-To determine the maximum tolerated dose (MTD)
Time Frame: Up to day 28 from the first dose (4 weeks).
MTD was defined as the previous dose level at which 2 out of 3 patients or 2 out of 6 patients experienced a DLT.
Part2- Objective response rate (ORR )
Time Frame: From first dose until disease progression or withdrawal from study, assessed up to 24 months.
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.
Secondary Outcomes
- 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)
- Time to reach maximum plasma concentration (T 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)
- Apparent terminal half-life (t1/2) 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)
- Area under plasma concentration versus time curve from zero to the 12 hour sampling time (AUC0-12) after single dose(Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 first dose)
- Area under plasma concentration versus time curve from zero to the 24 hour sampling time (AUC0-24) after single dose(Pre-dose, 0.5, 1, 1.5, 2, 4, 6, 8, 10, 12, 24 hours post-dose on Day 1 single dose)
- Objective response rate (ORR)- Part1(From first dose until disease progression or withdrawal from study, assessed up to 24 months.)
- Disease control rate (DCR)(From first dose until disease progression or withdrawal from study, assessed up to 24 months.)
- Duration of response (DoR)(From first dose until disease progression or withdrawal from study, assessed up to 24 months.)
- Progression-free survival (PFS)(From first dose until disease progression or withdrawal from study, assessed up to 24 months.)
- Overall survival (OS)-Part 2(From first dose until disease progression or withdrawal from study, assessed up to 24 months.)