Toripalimab and JS004 Combined With Platinum-based Chemotherapy for Relapsed and Extensive-stage Small Cell Lung Cancer

Toripalimab and JS004 Combined With Platinum-based Chemotherapy for Relapsed and Extensive-stage Small Cell Lung Cancer: a Single-center, Randomized Trial

For extensive-stage small cell lung cancer (SCLC), platinum-chemotherapy (cisplatin or carboplatin) combined with etoposide as the first-line treatment is recommended. However, the recurrence rate is extremely high after the initial first-line treatment. For those who relapse or progress within more than six minths after the end of the-first-line treatment, chose the current guideline recommendation trearment plan has the poor prognosis. A new immunotherapeutic strategy is needed to achieve better anti-tumor effects. JS004 is a new antibody targeting B and T lymphocyte attenuator (BTLA), which restrains immune cells; function and leads to immune escape of tumor cells. The combination of PD-1 and BTLA antibodies has shown a good therapeutic effect in solid tumors. This trial aims to investigate the efficacy and safety of the therapeutic regimen of toripalimab and JS004 combined with platinum-based doublet chemotherapy in extensive-stage SCLC or relapsed within more than six months after radical treatment SCLC.

Study Overview

• Status: Not yet recruiting
• Conditions: Small Cell Lung Cancer Extensive Stage; Small Cell Lung Cancer Recurrent
• Intervention / Treatment: Drug: Toripalimab; Drug: JS004; Drug: Etoposide; Drug: Platinum

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Peng Zhang, PhD; Phone Number: 02165115006; Email: zhangpeng1121@tongji.edu.cn

Study Locations

• China
  • Shanghai, China, 200433
    • Shanghai Pulmonary Hospital
    • Contact: Peng Zhang, PhD; Email: zhangpeng1121@tongji.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. The patient shall sign the Informed Consent Form;
2. Aged 18 ≥ years;
3. Histological or cytological diagnosis of SCLC by needle biopsy or EBUS, and extensive stage or recurrent confirmed by imageological examinations or relapsed within more than six months after radical treatment SCLC;
4. Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
5. Life expectancy is at least 12 weeks;
6. At least 1 measurable lesion according to RECIST 1.1;
7. Patients with good function of other main organs (liver, kidney, blood system, etc.);
8. Fertile female patients must voluntarily use effective contraceptives from the start of the trial to within 30 days after its completion, and urine or serum pregnancy test results within 7 days prior to enrollment are negative;
9. Unsterilized male patients must voluntarily use effective contraception during the trial period and for 30 days after its conclusion.

Exclusion Criteria:

1. Patients with a malignancy other than SCLC within five years prior to the start of this trial;
2. Participants with any unstable systemic disease (including uncontrolled hypertension, severe arrhythmia, etc.);
3. With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
4. Participants who are allergic to the test drug or any auxiliary materials;
5. Participants with active hepatitis B, hepatitis C or HIV;
6. Participants with Interstitial lung disease currently;
7. Pregnant or lactating women;
8. Any malabsorption;
9. Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
10. Other factors that researchers think it is not suitable for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Therapy With Toripalimab Combined With Platinum-based Doublet Chemotherapy; In this arm, 50 patients with extensive-stage small cell lung cancer or relapsed within more than 6 months after SCLC radical treatment will receive 4 circles of toripalimab combined with platinum-based doublet chemotherapy. Then patients received maintenance treatment with toripalimab until the disease progressed.	Drug: Toripalimab; Specified dose on specified days.; Drug: Etoposide; Specified dose on specified days.; Drug: Platinum; Specified dose on specified days.
Experimental: Therapy With Toripalimab and JS004 Combined With Platinum-based Doublet Chemotherapy; In this arm, 50 patients with extensive-stage small cell lung cancer or relapsed within more than 6 months after SCLC radical treatment will receive 4 circles of toripalimab and JS004 combined with platinum-based doublet chemotherapy. Then patients received maintenance treatment with toripalimab and JS004 until the disease progressed.	Drug: Toripalimab; Specified dose on specified days.; Drug: JS004; Specified dose on specified days.; Other Names: tifcemalimab; Drug: Etoposide; Specified dose on specified days.; Drug: Platinum; Specified dose on specified days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free survival (PFS)	It is defined as the time (months) from the first administration of drug in this study to the disease progression or death (including any cause of death in the case of no progression) as recorded in CRF, regardless of whether the patient exits from the treatment or receives other anti-cancer treatment before progression.	up to 60 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall survival (OS)	It is defined as the time (months) from enrollment to death of participant due to any cause. In the case of a patient who still survives at the time of analysis, the date of last contact will be taken as the censoring date.	up to 60 months
Objective response rate (ORR)	ORR is defined according to the RECIST v1.1 criteria.	up to 30 months
Treatment-related adverse event (TRAE)	TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.	Up to 30 months
Health related quality of life (HRQol)：EORTC-QLQ-C30	The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-C30 , Version 3). EORTC's QLQ-C30 (V3.0) is a core scale for lung cancer patients, with a total of 43 items. Among them, Item 29 and 30 are divided into seven grades, which are assigned with 1 to 7 scores according to the answer options.	up to 5 months
Health related quality of life (HRQol)：LC13	The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (LC13, Version 3).The items are divided into 4 grades: Not at All, A Little, Quite a Bit, and Very Much, assigned with 1 to 4 scores respectively. The higher score, the worse quality.	up to 5 months

Collaborators and Investigators

• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2024
• Primary Completion (Estimated): September 1, 2030
• Study Completion (Estimated): September 1, 2030

Study Registration Dates

• First Submitted: October 9, 2024
• First Submitted That Met QC Criteria: October 16, 2024
• First Posted (Actual): October 18, 2024

Study Record Updates

• Last Update Posted (Actual): October 18, 2024
• Last Update Submitted That Met QC Criteria: October 16, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: small cell lung cancer; Toripalimab; Recurrent; Extensive-stage; JS004
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Small Cell Lung Carcinoma; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Etoposide
• Other Study ID Numbers: LungMate-031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: The researchers will consider whether IPD is available to other researchers only after the paper is published.

Drug and device information, study documents

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