Stage III Non-small Cell Lung CancerPhase 2NCT05891080
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
A Phase 2 study testing Toripalimab, JS004 and Pemetrexed in people with Stage III Non-small Cell Lung Cancer, run by Shanghai Pulmonary Hospital, Shanghai, China.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage III Non-small Cell Lung Cancer
- What is being tested?
- Toripalimab, JS004 and Pemetrexed
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 124 participants
- Where
- No sites listed yet
- Study dates
- 1 Jul 2023to 1 Jul 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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;
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- 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.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
Suyu Wang contact
About this study
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
- Being tested
- Toripalimab, JS004, Pemetrexed, Nab-paclitaxel, Carboplatin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ToripalimabDrug
Specified dose on specified days.
JS004Drug
Specified dose on specified days.
PemetrexedDrug
Specified dose on specified days.
Nab-paclitaxelDrug
Specified dose on specified days.
CarboplatinDrug
Specified dose on specified days.
SurgeryProcedure or surgery
Patients with resectable tumor after neoadjuvant therapy will be treated with surgery.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Drug: Toripalimab; Drug: Pemetrexed; Drug: Nab-paclitaxel; Drug: Carboplatin; Procedure: Surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 30 months
Secondary outcomes (9)
Objective response rate (ORR)
ORR is defined according to the RECIST v1.1 criteria.
Measured: up to 30 months
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.
Measured: Up to 30 months
Treatment-related adverse event (TRAE)
TRAE is defined and classified according to NCI-CTCAE v5.0 in all participants.
Measured: Up to 30 months
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.
Measured: Up to 30 months
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.
Measured: Up to 30 months
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).
Measured: up to 60 months
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.
Measured: up to 60 months
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.
Measured: up to 5 months
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.
Measured: up to 5 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2023
- Study start1 Jul 2023 (estimated)
- Primary completion1 Jul 2025 (estimated)
- Study completion1 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage III Non-small Cell Lung CancerStudies of the same condition, open and under way.
- More trials run by Shanghai Pulmonary Hospital, Shanghai, ChinaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 124 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Peng Zhang, Shanghai Pulmonary Hospital, Shanghai, China
- Investigators
- Peng Zhang, PhD, Principal investigator, Shanghai Pulmonary Hospital, Shanghai, China
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05891080
- Sponsor's protocol ID
- LungMate-014
- Status last verified
- Jun 2023
- First submitted
- 22 May 2023
- Last updated
- 6 Jun 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: The researchers will consider whether IPD is available to other researchers only after the paper is published.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05891080
- Acronym / sponsor ID
- LungMate-014
- Conditions
- Stage III Non-small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 124 participants (estimated)
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, ChinaUniversity, hospital or other
- Study start
- 1 Jul 2023 (estimated)
- Primary completion
- 1 Jul 2025 (estimated)
- Study completion
- 1 Jul 2030 (estimated)
- First posted
- 6 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Safety run-in arm | Experimental | Drug: Toripalimab, Drug: JS004, Drug: Pemetrexed, Drug: Nab-paclitaxel, Drug: Carboplatin, Procedure: SurgeryIn 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. |
| JS004 arm | Experimental | Drug: Toripalimab, Drug: JS004, Drug: Pemetrexed, Drug: Nab-paclitaxel, Drug: Carboplatin, Procedure: SurgeryPatients 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. |
| Control arm | Active comparator | Drug: Toripalimab, Drug: Pemetrexed, Drug: Nab-paclitaxel, Drug: Carboplatin, Procedure: SurgeryPatients 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (10 listed)
- 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;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ToripalimabSpecified dose on specified days. | Drug | Control arm, JS004 arm, Safety run-in arm |
| JS004Specified dose on specified days. | Drug | JS004 arm, Safety run-in arm |
| PemetrexedSpecified dose on specified days. | Drug | Control arm, JS004 arm, Safety run-in arm |
| Nab-paclitaxelSpecified dose on specified days. | Drug | Control arm, JS004 arm, Safety run-in arm |
| CarboplatinSpecified dose on specified days. | Drug | Control arm, JS004 arm, Safety run-in arm |
| SurgeryPatients with resectable tumor after neoadjuvant therapy will be treated with surgery. | Procedure or surgery | Control arm, JS004 arm, Safety run-in arm |
Primary outcome
Pathologic complete response (PCR) rate
Time frame: Up to 30 months
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.
9 secondary outcomes
Objective response rate (ORR)
Time frame: up to 30 months
Major pathologic response (MPR) rate
Time frame: Up to 30 months
Treatment-related adverse event (TRAE)
Time frame: Up to 30 months
Rate of conversion from potentially resectable to resectable
Time frame: Up to 30 months
R0 resection rate
Time frame: Up to 30 months
Event-free survival (EFS)
Time frame: up to 60 months
Overall survival (OS)
Time frame: up to 60 months
EORTC-QLQ-C30 scale
Time frame: up to 5 months
EORTC-QLQ-L13 scale
Time frame: up to 5 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jun 2023.
- Individual participant dataSharing planned: Undecided. The researchers will consider whether IPD is available to other researchers only after the paper is published.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Suyu Wang contact
Peng Zhang, PhD principal investigator
Shanghai Pulmonary Hospital, Shanghai, China
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab, JS004 and Pemetrexed in people with Stage III Non-small Cell Lung Cancer, run by Shanghai Pulmonary Hospital, Shanghai, China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Peng Zhang, PhD (02165115006, zhangpeng1121@tongji.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathologic complete response (PCR) rate (time frame: Up to 30 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2023.