Advanced Non-small Cell Lung Cancer
Conditions
Brief summary
This is an open-label, two-part study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of SHR-A1811 for injection in subjects with advanced non-small cell lung cancer who have HER2 expression , amplification, or mutation
Interventions
DRUGSHR-A1811
Phase 1 Drug: SHR-A1811 There are four pre-defined dose regimens . Subjects will be enrolled with an initial dose Phase 2 Drug: SHR-A1811 Doses will be determined from Phase 1
Sponsors
Jiangsu HengRui Medicine Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm study of SHR-A1811
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Able and willing to provide a written informed consent 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 3. advanced non-small cell lung cancer with HER2 expression , amplification, or mutation 4. has previously received platinum-based chemotherapy for advanced or metastatic NSCLC, has developed disease progression during or after treatment, or is unable to tolerate platinum-based chemotherapy. 5. There is at least one measurable lesion according to RECIST V1.1 criteria
Exclusion criteria
1. Has unresolved toxicities from previous anticancer therapy, defined as toxicities not yet resolved to NCI-CTCAE version 5.0 grade ≤ 1. 2. Has received HER2 antibody drug conjugates, 3. Central nervous system metastasis or meningeal metastasis with clinical symptoms 4. Has active infection requiring systemic treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1:Incidence of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811 | From Day 1 to90 days after last dose ，appropriately to 3 years | Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0) |
| Phase 1:Severity of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811 | From Day 1 to90 days after last dose ，appropriately to 3 years | Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0) |
| Phase1: Maximum tolerated dose (MTD) | 12 months | Incidence rate and category of dose limiting toxicities (DLTs) during the first 21-day cycle of SHR-A1811 treatment |
| Phase 1: Recommended Phase 2 dose (RP2D) | 12 months | RP2D was determined based on the safety, tolerability, PK, immunogenicity data and efficacy information obtained |
| Phase2:ObjectiveResponse Rate (ORR) | Subjects were evaluated on tumor imaging every 6 weeks after treatment initiation and every 12 weeks after 54 weeks, until imaging progression, initiation of new antitumor therapy, loss of follow-up, and death，appropriately to 3 years | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase2:ObjectiveResponse Rate (ORR) | appropriately to 3 years | As assessed by RECIST v1.1 , as assessed by investigator |
| Phase2:Duration of response (DOR) | appropriately to 3 years | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator |
| Phase 1：PK parameter ：Tmax of SHRA1811 | appropriately to 3 years | Time to maximal concentration (Tmax) of SHR-A1811 |
| Phase2:Overall survival (OS) | Approximately 5 years after last subject enrolled | — |
| Phase2:Disease control rate (DCR) | appropriately to 3 years | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator |
| Phase1:PK parameter: Cmax of SHR-A1811 | appropriately to 3 years | Maximal concentration (Cmax) of SHR-A1811 |
| Phase1:PK parameter: AUC0-t of SHR-A1811 | appropriately to 3 years | AUC computed from time zero to the time of the last quantifiable concentration (AUC0-t) of SHR-A1811 |
| Phase1:Immunogenicity of SHR-A1811 | Immunogenicity sample collection time points include: within 30 min before administration of C1D1, C2D1, C3D1, C4D1, C6D1 and C8D1 starting from cycle 11 only in every 3 cycles ,appropriately to 3 years | Including anti-drug antibody and/or neutralizing antibody |
| Phase2:Progression Free Survival (PFS) | appropriately to 3 years | As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator |
Countries
China
Outcome results
None listed