A Study of SHR-A1811 in Subjects With Advanced Non-small Cell Lung Cancer

Phase I/II Clinical Study of 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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: SHR-A1811

• Study Type: Interventional
• Enrollment (Actual): 157
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200030
      • Shanghai Chest Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SHR-A1811; SHR-A1811 was administered intravenously every 3 weeks (Q3W) until discontinuation treatment	Drug: SHR-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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1:Incidence of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811	Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0)	From Day 1 to90 days after last dose ，appropriately to 3 years
Phase 1:Severity of Adverse Events (AEs) by CTCAE v5.0 of SHR-A1811	Assess safety and tolerability of SHR-A1811 by way of adverse events (CTCAE v5.0)	From Day 1 to90 days after last dose ，appropriately to 3 years
Phase1: Maximum tolerated dose (MTD)	Incidence rate and category of dose limiting toxicities (DLTs) during the first 21-day cycle of SHR-A1811 treatment	12 months
Phase 1: Recommended Phase 2 dose (RP2D)	RP2D was determined based on the safety, tolerability, PK, immunogenicity data and efficacy information obtained	12 months
Phase2:ObjectiveResponse Rate (ORR)	As assessed by RECIST v1.1 , as assessed by independent review committee (IRC)	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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1：PK parameter ：Tmax of SHRA1811	Time to maximal concentration (Tmax) of SHR-A1811	appropriately to 3 years
Phase1:PK parameter: Cmax of SHR-A1811	Maximal concentration (Cmax) of SHR-A1811	appropriately to 3 years
Phase1:PK parameter: AUC0-t of SHR-A1811	AUC computed from time zero to the time of the last quantifiable concentration (AUC0-t) of SHR-A1811	appropriately to 3 years
Phase1:Immunogenicity of SHR-A1811	Including anti-drug antibody and/or neutralizing antibody	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
Phase2:Progression Free Survival (PFS)	As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator	appropriately to 3 years
Phase2:ObjectiveResponse Rate (ORR)	As assessed by RECIST v1.1 , as assessed by investigator	appropriately to 3 years
Phase2:Duration of response (DOR)	As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator	appropriately to 3 years
Phase2:Disease control rate (DCR)	As assessed by RECIST v1.1 , as assessed by independent review committee (IRC) and investigator	appropriately to 3 years
Phase2:Overall survival (OS)		Approximately 5 years after last subject enrolled

Collaborators and Investigators

• Sponsor: Jiangsu HengRui Medicine Co., Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): April 23, 2021
• Primary Completion (Estimated): June 1, 2025
• Study Completion (Estimated): June 1, 2025

Study Registration Dates

• First Submitted: March 25, 2021
• First Submitted That Met QC Criteria: March 25, 2021
• First Posted (Actual): March 26, 2021

Study Record Updates

• Last Update Posted (Actual): June 13, 2024
• Last Update Submitted That Met QC Criteria: June 11, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: SHR-A1811-I-103

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No