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

Stage III Non-small Cell Lung Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05891080
• Other study ID #: LungMate-014
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: July 1, 2023
• Est. completion date: July 1, 2030

Study information

• Verified date: June 2023
• Source: Shanghai Pulmonary Hospital, Shanghai, China
• Contact: Peng Zhang, PhD
• Phone: 02165115006
• Email: zhangpeng1121[@]tongji.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 124
• Est. completion date: July 1, 2030
• Est. primary completion date: July 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. The patient shall sign the Informed Consent Form.

2. Aged 18 = years.

3. Histological or cytological diagnosis of NSCLC by needle biopsy, and stage IIIB-IIIC confirmed by imageological examinations (CT, PET-CT or EBUS).

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. Patients with lung function can tolerate surgery;

9. Without systematic metastasis (including M1a, M1b and M1c);

10. 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.

11. 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).

Exclusion Criteria:

1. 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;

2. 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;

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 Interstitial lung disease currently;

6. Participants with active hepatitis B, hepatitis C or HIV;

7. Pregnant or lactating women;

8. Participants suffering from nervous system diseases or mental diseases that cannot cooperate;

9. Participated in another therapeutic clinical study;

10. Other factors that researchers think it is not suitable for enrollment.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Stage III Non-small Cell Lung Cancer

Intervention

Drug:
• Toripalimab
Specified dose on specified days.
• JS004
Specified dose on specified days.
• Pemetrexed
Specified dose on specified days.
• Nab-paclitaxel
Specified dose on specified days.
• Carboplatin
Specified dose on specified days.

Procedure:
• Surgery
Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Shanghai Pulmonary Hospital, Shanghai, China

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Objective response rate (ORR)	ORR is defined according to the RECIST v1.1 criteria.	up to 30 months
Secondary	Major pathologic response (MPR) rate	MPR rate is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants.	Up to 30 months
Secondary	Treatment-related adverse event (TRAE)	TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.	Up to 30 months
Secondary	Rate of conversion from potentially resectable to resectable	Rate of conversion from potentially resectable to resectable is defined as the proportion of participants with potentially resectable tumor conversed into resectable tumor in all participants with potentially resectable tumor.	Up to 30 months
Secondary	R0 resection rate	R0 resection rate is defined as the proportion of participants who have achieved R0 resection (complete resection with no residual tumor cell in the resection margin) in all participants.	Up to 30 months
Secondary	Event-free survival (EFS)	Event-free survival (EFS) is defined as the length of time (months) from randomization to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause. Participants who don't undergo surgery for reason other than progression will be considered to have an event at progression or death. Progression is defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).	up to 60 months
Secondary	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
Secondary	EORTC-QLQ-C30 scale	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 30 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. The other 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
Secondary	EORTC-QLQ-L13 scale	The assessment is made according to the Quality of Life Scale for Lung Cancer Patients (EORTC-QLQ-LC13). EORTC's QLQ-LC13 is a core scale for lung cancer patients, with a total of 13 items. 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