Clinical trial NCT04797702: Glumetinib Combined With Toripalimab in the Treatment of Relapsed or Metastatic Non-small Cell Lung Cancer.
Official title: 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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Relapsed or Metastatic Non-small Cell Lung Cancer
Lead sponsor: Shanghai Junshi Bioscience Co., Ltd.
Sponsor class: OTHER
First posted: 2021-03-15
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion criteria:

1. 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;
2. PD - L1 expression of 1% or higher.
3. 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;
4. At least 1 measurable tumor lesion according to RECIST1.1 criteria.
5. Subjects must provide valid and qualified tissue samples (fresh biopsy or preserved tumor tissue samples are acceptable, but fresh biopsy samples are preferred).
6. ECOG score ≤1 point;
7. Sufficient function of bone marrow, liver and kidney organs.

Exclusion criteria:

1. Pathological diagnosis confirmed the presence of small cell lung cancer;
2. The patient was currently participating in and receiving other studies or had previously received another c-Met inhibitor;
3. There are mutations/rearrangements of EGFR, ALK, ROS1, Met14 exon skipping;

Primary outcomes:
measure: The type, frequency, severity and outcome of adverse events (TEAE) and serious adverse events (SAE) that occurred during the treatment period. (Phase Ib)
timeFrame: 2 years
measure: Number of prticipants with abnormal laboratory values and/or Adverse Events that are related to treatment. (Phase Ib)
timeFrame: 2 years
measure: Number of participants with abnormal vital signs values and/or Adverse Events that are related to treatment. (Phase Ib)
timeFrame: 2 years
measure: Number of participants with abnormal ECG and echocardiography values /or Adverse Events that are related to treatment. (Phase Ib)
timeFrame: 2 years
measure: Number of participants with aphysical examination values /or Adverse Events that are related to treatment.(Phase Ib)
timeFrame: 2 years
measure: To determine the recommended dose for the phase II study (RP2D) .(Phase Ib)
timeFrame: 2 years
measure: Investigator-assessed objective response rate (ORR) (Phase 2)
timeFrame: 2 years
Secondary outcomes:
measure: Investigator-assessed objective response rate (ORR). (Phase 1b)
timeFrame: 2 years
measure: Investigator-assessed progression-free survival (PFS) . (Phase 1b)
timeFrame: 2 years
measure: Investigator-assessed duration of remission(DoR). (Phase 1b)
timeFrame: 2 years
measure: Investigator-assessed disease control rate (DCR). (Phase 1b)
timeFrame: 2 years
measure: Investigator-assessed overall survival (OS) and 1-year OS rate.(Phase 1b)
timeFrame: 2 years
measure: Investigator-assessed objective response rate (ORR). (Phase II)
timeFrame: 2 years
measure: Investigator-assessed progression-free survival (PFS) . (Phase II)
timeFrame: 2 years
measure: Investigator-assessed duration of remission(DoR). (Phase II)
timeFrame: 2 years
measure: Investigator-assessed disease control rate (DCR). (Phase II)
timeFrame: 2 years
measure: Investigator-assessed overall survival (OS) and 1 year OS rate. (Phase II)
timeFrame: 2 years
measure: The type, frequency, severity and outcome of adverse events (TEAE) and serious adverse events (SAE) that occurred during the treatment period. (Phase II)
timeFrame: 2 years
measure: Number of prticipants with abnormal laboratory values and/or Adverse Events that are related to treatment. (Phase II)
timeFrame: 2 years
measure: Number of participants with abnormal vital signs values and/or Adverse Events that are related to treatment.(Phase II)
timeFrame: 2 years
measure: Number of participants with abnormal ECG and echocardiography values /or Adverse Events that are related to treatment.(Phase II)
timeFrame: 2 years
measure: Number of participants with aphysical examination values /or Adverse Events that are related to treatment.(Phase II)
timeFrame: 2 years
measure: ORR in PD-L1 positive and negative populations.
timeFrame: 2 years
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Guangdong Provincial People's Hospital
state: Guangdong
Study officials:
References: