A Open-label, Multi-center Phase Ib/II Clinical Study of Glumetinib Combined With Toripalimab in Patients With Relapsed or Metastatic Non-small Cell Lung Cancer Who Have Failed or Are Intolerant to Standard Therapy.
Trial Snapshot
- Phase
- Phase 1
- Status
- Terminated
- Sponsor
- Enrollment
- 6
- Locations
- 1
- Primary Endpoint
- The type, frequency, severity and outcome of adverse events (TEAE) and serious adverse events (SAE) that occurred during the treatment period. (Phase Ib)
Study Overview
Brief Summary
This is an open-label, multicenter Phase Ib/II registration clinical study, consisting of two parts: the Phase Ib dose-climbing study and the Phase II efficacy exploration study.
Phase Ib :
Phase Ib is a multicenter, single-arm study evaluating the safety, tolerability, and preliminary efficacy of SCC244 combined with Toripalimab in patients with advanced relapsed or metastatic non-small cell lung cancer who have failed standard therapy.At the start of the study, MTPI2 was used to guide toxicity monitoring and dose climbing in combination with Toripalimab (240mg intravenous every 3 weeks), with 5 subjects planned to be enrolled in each dose group.The SMC will decide whether to add the new dose level and sample size based on the latest study data available.The MTD or recommended phase II dose (RP2D) will be determined during the phase Ib study on the basis of the latest availablestudy data, and the phase II study will commence once the MTD or recommended phase II dose (RP2D) is confirmed.
Phase II:
Phase II is a multicenter, open-label, single-arm study evaluating the efficacy and safety of a recommended dose of glumetinib combined with Toripalimab in patients with relapsed, metastatic non-small cell lung cancer who have failed standard therapy.The SMC determined the dose group for the Phase II study based on the safety and initial efficacy data of the Phase Ib subjects.Approximately 62 evaluable subjects will be enrolled, with the recommended dose of glutmetinib once daily and Toripalimab 240mg every 3 weeks.
Every 21 days is a treatment cycle until the subject develops disease progression,intolerable toxicity, has used JS001 for 2 years, the informed consent is withdrawn, the investigator considers that the subject should not continue the medication, lost to follow-up, death occurs, or the study is terminated, whichever comes first.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Subsubjects with histologically or cytologically confirmed NSCLC, clinically diagnosed as locally advanced (stage IIIB or IIIC) and stage IV NSCLC (according to AJCC 8th edition staging), EGFR wild-type, negative for ALK and ROS1 rearrangement, and no Met exon14 skipping mutation; genetic testing is not mandatory for subjects with squamous cell cancer;
- •PD - L1 expression of 1% or higher.
- •Non-small cell lung cancer patients following failure of or were intolerance to previous standard treatment (chemotherapy and immunotherapy alone or in combination) and received no more than third-line treatment;
- •At least 1 measurable tumor lesion according to RECIST1.1 criteria.
- •Subjects must provide valid and qualified tissue samples (fresh biopsy or preserved tumor tissue samples are acceptable, but fresh biopsy samples are preferred).
- •ECOG score ≤1 point;
- •Sufficient function of bone marrow, liver and kidney organs.
Exclusion Criteria
- •Pathological diagnosis confirmed the presence of small cell lung cancer;
- •The patient was currently participating in and receiving other studies or had previously received another c-Met inhibitor;
- •There are mutations/rearrangements of EGFR, ALK, ROS1, Met14 exon skipping;
Arms & Interventions
Experimental group
Glumetinib combined with Toripalimab
Intervention: Glumetinib combined with Toripalimab (Combination Product)
Outcomes
Primary Outcomes
The type, frequency, severity and outcome of adverse events (TEAE) and serious adverse events (SAE) that occurred during the treatment period. (Phase Ib)
Time Frame: 2 years
The toxicity was evaluated according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (version 5.0) Grade.
Number of participants with aphysical examination values /or Adverse Events that are related to treatment.(Phase Ib)
Time Frame: 2 years
A full physical examination in the screening period and at the end-of-treatment visit, including head, eyes, ears, nose, throat, neck, heart, chest (including lungs), abdomen, four limbs, skin, lymph nodes, nervous system, and subject's general condition. Body height and body weight are measured at the first visit, and then body weight is measured at each of the subsequent visits. Targeted physical examination will be conducted at other visits by the investigator.
Number of participants with abnormal vital signs values and/or Adverse Events that are related to treatment. (Phase Ib)
Time Frame: 2 years
The vital signs include body temperature, heart rate, and respiratory frequency and blood pressure.
Number of participants with abnormal ECG and echocardiography values /or Adverse Events that are related to treatment. (Phase Ib)
Time Frame: 2 years
During the screening period, it is necessary to repeat the inspection three times before the first administration, with an interval of about 5 minutes between each time. Calculate the QTc interval and calculate the mean (corrected using Fridericia's formula). If the inspection time in the screening period is ≤ 7 days before the first administration, the review may not be necessary according to the judgment of the investigator. Check once a week in the 1st cycle of phase Ib, check once on the 1st and 15th days of the 2nd cycle, and check once every 3 weeks from the 3rd cycle. Use echocardiography or multi-gate angiography scan to check the left ventricular ejection fraction.
Number of prticipants with abnormal laboratory values and/or Adverse Events that are related to treatment. (Phase Ib)
Time Frame: 2 years
Laboratory values include 1. Routine blood test: Including complete blood count with differential. 2.Routine urine test: including specific gravity, pH, urine glucose, protein, ketone bodies and blood cell. 3.Serum biochemistry: Including ALT, AST, ALP, TP, ALB, TBIL, DBIL, GLU, BUN/UREA, Cr, K+, Na+, Cl-, Ca2+, P, TG, TC, HDL, LDL, and AMY/LIP. 4.Coagulation function: Including at least international normalized ratio (INR), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT); if the international normalized ratio (INR) is not available, replace it with prothrombin time (PT). 5.Thyroid function test includes: serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4); if FT3 and FT4 are not available, replace them with T3 and T4. 6.Troponin I or troponin T content: only during the screening period and when clinical indications (such as cardiac events occur).
To determine the recommended dose for the phase II study (RP2D) .(Phase Ib)
Time Frame: 2 years
Phase Ib is the dose-escalation period, and the optimal dose of Glumetinib combined with Toripalimab was explored as the recommended dose for the phase II clinical study.
Investigator-assessed objective response rate (ORR) (Phase 2)
Time Frame: 2 years
ORR refers to the percentage of subjects with confirmed CR or PR according to RECIST1.1
Secondary Outcomes
- Investigator-assessed objective response rate (ORR). (Phase 1b)(2 years)
- Investigator-assessed objective response rate (ORR). (Phase II)(2 years)
- Investigator-assessed overall survival (OS) and 1 year OS rate. (Phase II)(2 years)
- The type, frequency, severity and outcome of adverse events (TEAE) and serious adverse events (SAE) that occurred during the treatment period. (Phase II)(2 years)
- Investigator-assessed duration of remission(DoR). (Phase 1b)(2 years)
- Investigator-assessed duration of remission(DoR). (Phase II)(2 years)
- Number of participants with abnormal vital signs values and/or Adverse Events that are related to treatment.(Phase II)(2 years)
- Number of participants with abnormal ECG and echocardiography values /or Adverse Events that are related to treatment.(Phase II)(2 years)
- Number of participants with aphysical examination values /or Adverse Events that are related to treatment.(Phase II)(2 years)
- Investigator-assessed disease control rate (DCR). (Phase II)(2 years)
- Investigator-assessed progression-free survival (PFS) . (Phase 1b)(2 years)
- Investigator-assessed disease control rate (DCR). (Phase 1b)(2 years)
- Investigator-assessed overall survival (OS) and 1-year OS rate.(Phase 1b)(2 years)
- Investigator-assessed progression-free survival (PFS) . (Phase II)(2 years)
- ORR in PD-L1 positive and negative populations.(2 years)
- Number of prticipants with abnormal laboratory values and/or Adverse Events that are related to treatment. (Phase II)(2 years)