Neoadjuvant Therapy With Toripalimab and JS004 Combined With Platinum-based Doublet Chemotherapy for Resectable or Potentially Resectable Stage III Non-small Cell Lung Cancer: A Randomised Controlled, Open-label, Phase 2 Trial

NCT05891080 | Not Yet Recruiting Phase 2

• 1 other identifier: LungMate-014
• Study Type: interventional
• Target: 124
• Locations: 0 countries
• Sites: N/A

Brief Summary

For stage III non-small cell lung cancer (NSCLC), neoadjuvant chemotherapy plus PD-1 antibody is recommended. However, most patients could not achieve complete pathological response (CPR). New immunotherapeutic strategy is needed to achieve higher CPR rate. JS004 is a new antibody targeting B and T lymphocyte attenuator (BTLA) which restrains the function of immune cells and leads to immune escape of tumor cells. The combination of PD-1 antibody and BTLA antibody has shown good therapeutic effect in solid tumors. This trial aims to investigate the efficacy and safety of the therapeutic regimen of toripalimab and JS004 plus chemotherapy in stage III NSCLC.

Conditions

Stage III Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Pathologic complete response (PCR) rate

  PCR rate is defined as the proportion of participants who have achieved pathologic complete response (on routine hematoxylin and eosin staining, no tumor cell can be found in tumor bed or lymph node) in all participants.

  Up to 30 months

Secondary Outcomes (9)

• Objective response rate (ORR)

  up to 30 months

• Major pathologic response (MPR) rate

  Up to 30 months

• Treatment-related adverse event (TRAE)

  Up to 30 months

• Rate of conversion from potentially resectable to resectable

  Up to 30 months

• R0 resection rate

  Up to 30 months

Study Arms (3)

Safety run-in arm

EXPERIMENTAL

In this arm, 6 patients with resectable or potentially resectable stage III non-small cell lung cancer will receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Drug: Toripalimab; Drug: JS004; Drug: Pemetrexed; Drug: Nab-paclitaxel; Drug: Carboplatin; Procedure: Surgery

JS004 arm

EXPERIMENTAL

Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab and JS004 combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Drug: Toripalimab; Drug: JS004; Drug: Pemetrexed; Drug: Nab-paclitaxel; Drug: Carboplatin; Procedure: Surgery

Control arm

ACTIVE COMPARATOR

Patients with resectable or potentially resectable stage III non-small cell lung cancer will be randomized into this arm (59 patients) and receive 4 circles of neoadjuvant toripalimab combined with platinum-based doublet chemotherapy and those resectable after neoadjuvant therapy will be treated with surgery.

Drug: Toripalimab; Drug: Pemetrexed; Drug: Nab-paclitaxel; Drug: Carboplatin; Procedure: Surgery

Interventions

Toripalimab DRUG

Specified dose on specified days.

Control arm; JS004 arm; Safety run-in arm

JS004 DRUG

Specified dose on specified days.

JS004 arm; Safety run-in arm

Pemetrexed DRUG

Specified dose on specified days.

Control arm; JS004 arm; Safety run-in arm

Nab-paclitaxel DRUG

Specified dose on specified days.

Control arm; JS004 arm; Safety run-in arm

Carboplatin DRUG

Specified dose on specified days.

Control arm; JS004 arm; Safety run-in arm

Surgery PROCEDURE

Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

Control arm; JS004 arm; Safety run-in arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The patient shall sign the Informed Consent Form.
• Aged 18 ≥ years.
• Histological or cytological diagnosis of NSCLC by needle biopsy, and stage IIIB-IIIC confirmed by imageological examinations (CT, PET-CT or EBUS).
• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.
• Life expectancy is at least 12 weeks.
• At least 1 measurable lesion according to RECIST 1.1.
• Patients with good function of other main organs (liver, kidney, blood system, etc.)
• Patients with lung function can tolerate surgery;
• Without systematic metastasis (including M1a, M1b and M1c);
• Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
• Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of toripalimab (whichever is later).

You may not qualify if:

• Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment;
• Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (\>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;
• With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
• Participants who are allergic to the test drug or any auxiliary materials;
• Participants with Interstitial lung disease currently;
• Participants with active hepatitis B, hepatitis C or HIV;
• Pregnant or lactating women;
• Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
• Participated in another therapeutic clinical study;
• Other factors that researchers think it is not suitable for enrollment.

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

toripalimab; Pemetrexed; 130-nm albumin-bound paclitaxel; Carboplatin; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Coordination Complexes; Organic Chemicals

Study Officials

• Peng Zhang, PhD

  Shanghai Pulmonary Hospital, Shanghai, China

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Peng Zhang, PhD

CONTACT

02165115006; zhangpeng1121@tongji.edu.cn

Suyu Wang

CONTACT

wangsuyv357311854@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: May 22, 2023
• First Posted: June 6, 2023
• Study Start: July 1, 2023
• Primary Completion: July 1, 2025
• Study Completion (Estimated): July 1, 2030
• Last Updated: June 6, 2023

Record last verified: 2023-06