Carcinoma, Non-Small-Cell LungPhase 2TOPLINENCT06269211
Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression
A Phase 2 study testing Toripalimab in people with Carcinoma, Non-Small-Cell Lung, run by Ruijin Hospital at 2 sites in China.
Trial summary
The study is a prospective, open label, multicenter, single arm Phase II clinical trial, aiming to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Carcinoma, Non-Small-Cell Lung
- What is being tested?
- Toripalimab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 2 sitesChina
- Study dates
- 20 Apr 2024to 31 Jan 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
- Men and women aged ≥ 18 years old.
- Baseline tumor tissues have to be obtained through biopsy (percutaneous or transbronchial) or surgery at study center.
- Histologically confirmed diagnosis of primary non-small lung cancer on non-squamous histology.
- Pre-treatment stage as clinical II-IIIB (AJCC/UICC 8th Edition) (stage IIIB excludes N3 disease); curative resectability has to be explicitly verified by the experienced surgical investigator.
- Confirmation by the central laboratory that the tumor harbors EGFR mutations either sensitive mutations, uncommon mutations or complex mutations.
- Have a PD-L1 tumor proportion score (TPS) ≥ 1% determined by IHC at the central laboratory. In order to balance patients with high PD-L1 expression (≥50%) and low PD-L1 expression (1-49%), we planned to enroll PD-L1 high and low patients at a ratio of 1:1.
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- Have not received prior systemic treatment for NSCLC.
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
- Expected survival ≥ 3 months.
- Adequate blood and organ function.
Who cannot join
- Patients with histologically confirmed squamous cell carcinoma, combined small cell carcinoma and large cell carcinoma.
- Molecular testing confirmed ALK translocation.
- Treatment with prior systemic cancer therapy for the current lung cancer at any time (chemotherapy, radiotherapy, target therapy, ablation, and any other local or systemic therapy).
- Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
- Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications. Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
- Subjects with a history of interstitial lung disease, pneumonitis, or poorly controlled lung disease (including pulmonary fibrosis, acute lung diseases).
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- Severe chronic or active infections that require systemic antimicrobial, antifungal, or antiviral treatment, including tuberculosis infections.
- Patients with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carriers with HBV DNA ≥ 500 IU/mL [2500 copies/mL] should be excluded.
- Has known active hepatitis C virus (HCV). Active HCV is defined by positive tests for HCV Ab and quantitative HCV RNA.
- Known positive history or positive test for Human Immunodeficiency Virus (HIV).
- The investigator believes that there is a high risk of bleeding (such as esophageal varices with bleeding risk, local active ulcer lesions) or active hemoptysis.
- History of allergy to study drug components.
- Pregnant and lactating women are excluded.
- Fertile men or their female partners (women of childbearing potential, WOCBP) who are not willing to use contraception.
- Any medical, mental or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or understand the patient information.
- The investigator believes that there are factors that can increase medication risk or confuse outcome judgment.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Recruiting
Guangdong Provincial People's Hospital
Guangzhou, Guangdong, 510180
Wen-zhao Zhong, MD,PhD, +86 20 83827812 ext. 51221, syzhongwenzhao@scut.edu.cn
Wen-zhao Zhong, MD,PhD
- Recruiting
Ruijin Hospital, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai Municipality, 200025
Hecheng Li, MD,PhD, 0086-021-64370045, lihecheng2000@hotmail.com
Yichao Han, MD,PhD, 0086-19327440494, trey_e@foxmail.com
About this study
Official title: Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression: a Prospective, Open-label, Multicenter, Single-arm Phase II Clinical Study
The study is a prospective, open label, multicenter, single arm Phase II clinical trial, aiming to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients. This study will provide valuable information for further clinical trials of neoadjuvant Toripalimab and other immune checkpoint inhibitors in NSCLC patients with EGFR mutations and PD-L1 positive expression.
Read the detailed description
For resectable locally advanced non-small cell lung cancer (NSCLC), the combination of neoadjuvant therapy and surgery has benefited the patients and has become a clinical routine and guideline recommended treatment. Among the East Asian NSCLC population, about 30% are positive for EGFR driver gene mutations. The efficacy of this population receiving neoadjuvant chemotherapy and EGFR inhibitors is limited, and their optimal neoadjuvant treatment strategy is still unclear. The neoadjuvant immunotherapy has achieved good therapeutic effects in driver-negative NSCLC patients, and is superior in PD-L1 expression positive patients.
Based on the above evidence, the investigators plan to conduct a prospective, open label, multicenter, single arm Phase II clinical study to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients.
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Being tested
- Toripalimab
- 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
240mg IV, Q3W
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab | Experimental | Neoadjuvant Toripalimab 240 mg IV on cycle 1 day 1 (C1D1), C2D1 and C3D1 before radical surgery for lung cancer. The participants will attend follow-up visits based on molecular residual disease (MRD) and receive adjuvant treatment including EGFR-TKI or chemotherapy if recommended. Receives: Drug: Toripalimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Major Pathological Response (MPR)
Defined as the incidence rate in postoperative pathology where the percentage of surviving tumor cells in the tumor bed is ≤ 10%, regardless of the presence or absence of live tumor cells in the lymph nodes.
Measured: MPR will be assessed within 2 weeks after surgery
Secondary outcomes (6)
Pathological Complete Response (pCR)
Defined as the proportion of patients in postoperative pathology who have no residual live tumor cells in the primary tumor bed or in all excised lymph nodes.
Measured: pCR will be assessed within 2 weeks after surgery
Objective Response Rate (ORR)
Based on the solid tumor evaluation criteria (RECIST 1.1), the sum of the proportions of complete and partial remission evaluated by imaging
Measured: Tumor response will be evaluated within 30 days after last dose of neoadjuvant treatment
2-year Event Free Survival (EFS)
EFS is defined as the time from the first use of the investigational drug to any of the following events (whichever occurs first): the investigator assessed the disease progression based on imaging according to RECIST 1.1 and therefore was unable to receive curative surgery, local or distant recurrence, or death from any cause. A 2-year EFS is used as a secondary endpoint.
Measured: 2 years after the date of initiation of neoadjuvant treatment
2-year Overall Survival (OS)
OS is defined as the date from the first use of the investigational drug until death from any cause. A 2-year OS is used as a secondary endpoint.
Measured: 2 years after the date of initiation of neoadjuvant treatment
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
The safety evaluation will be based on weekly blood routine tests, liver and kidney function, electrolyte analysis, etc., and adverse reactions of level 3 or above will be recorded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).
Measured: From date of neoadjuvant treatment until surgery was applied during study period or up to at least 90 days after last dose.
Feasibility (Number of Participants Who Finished Neoadjuvant therapy and Receive Surgery Within 3-6 Weeks After Neoadjuvant Therapies)
Among patients who have been evaluated as operable after completing neoadjuvant therapy, a surgical period of no more than 42 days from the completion of neoadjuvant therapy is defined as feasible.
Measured: 6 weeks after last dose of neoadjuvant treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2024
- Study start20 Apr 2024
- Primary completion31 Jan 2027 (estimated)
- Study completion31 Jan 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Carcinoma, Non-Small-Cell LungStudies of the same condition, open and under way.
- More trials run by Ruijin HospitalThe 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
- Not applicable
- Intervention model
- Single group
- Model description
- This study has only one arm, neoadjuvant Toripalimab treatment arm. Primary endpoint is MPR. We apply the optimal design of Simon's two-stage model to calculate the sample size and set both sides α= 0.05 and power=0.8, resulting in a total sample size of 29. Among them, 10 patients will be enrolled in the first stage. If the number of MPR cases in the first stage is less than or equal to 1, the study will be terminated in the early stage; On the contrary, participants in the second stage will continue to be enrolled. If the total number of MPR cases is greater than or equal to 5 after the completion of the second stage, the study is considered positive.
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ruijin Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Guangdong Provincial People's Hospital
- Responsible party
- Principal investigator, Hecheng Li M.D., Ph.D, Ruijin Hospital
- Investigators
- Hecheng Li, PhD, MD, Principal investigator, Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06269211
- Sponsor's protocol ID
- RTS-019
- Acronym
- TOPLINE
- Status last verified
- Nov 2024
- First submitted
- 12 Feb 2024
- Last updated
- 18 Nov 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Toripalimab for Clinically Stage II-IIIB Resectable Non-small Cell Lung Cancer with EGFR Mutation and PD-L1 Positive Expression: a Prospective, Open-label, Multicenter, Single-arm Phase II Clinical Study
- ClinicalTrials.gov ID
- NCT06269211
- Acronym / sponsor ID
- TOPLINE / RTS-019
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Ruijin HospitalUniversity, hospital or other
- Collaborators
- Guangdong Provincial People's Hospital
- Study start
- 20 Apr 2024 (actual)
- Primary completion
- 31 Jan 2027 (estimated)
- Study completion
- 31 Jan 2030 (estimated)
- First posted
- 21 Feb 2024 (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.
The study is a prospective, open label, multicenter, single arm Phase II clinical trial, aiming to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients. This study will provide valuable information for further clinical trials of neoadjuvant Toripalimab and other immune checkpoint inhibitors in NSCLC patients with EGFR mutations and PD-L1 positive expression.
Detailed description
For resectable locally advanced non-small cell lung cancer (NSCLC), the combination of neoadjuvant therapy and surgery has benefited the patients and has become a clinical routine and guideline recommended treatment. Among the East Asian NSCLC population, about 30% are positive for EGFR driver gene mutations. The efficacy of this population receiving neoadjuvant chemotherapy and EGFR inhibitors is limited, and their optimal neoadjuvant treatment strategy is still unclear. The neoadjuvant immunotherapy has achieved good therapeutic effects in driver-negative NSCLC patients, and is superior in PD-L1 expression positive patients.
Based on the above evidence, the investigators plan to conduct a prospective, open label, multicenter, single arm Phase II clinical study to explore the use of neoadjuvant Toripalimab for clinically stage II-IIIB NSCLC patients with EGFR mutations and PD-L1 positive expression, providing a novel perspective for further improving the prognosis of NSCLC patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This study has only one arm, neoadjuvant Toripalimab treatment arm. Primary endpoint is MPR. We apply the optimal design of Simon's two-stage model to calculate the sample size and set both sides α= 0.05 and power=0.8, resulting in a total sample size of 29. Among them, 10 patients will be enrolled in the first stage. If the number of MPR cases in the first stage is less than or equal to 1, the study will be terminated in the early stage; On the contrary, participants in the second stage will continue to be enrolled. If the total number of MPR cases is greater than or equal to 5 after the completion of the second stage, the study is considered positive.
| Arm | Type | Receives |
|---|---|---|
| Toripalimab | Experimental | Drug: ToripalimabNeoadjuvant Toripalimab 240 mg IV on cycle 1 day 1 (C1D1), C2D1 and C3D1 before radical surgery for lung cancer. The participants will attend follow-up visits based on molecular residual disease (MRD) and receive adjuvant treatment including EGFR-TKI or chemotherapy if recommended. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Men and women aged ≥ 18 years old.
- Baseline tumor tissues have to be obtained through biopsy (percutaneous or transbronchial) or surgery at study center.
- Histologically confirmed diagnosis of primary non-small lung cancer on non-squamous histology.
- Pre-treatment stage as clinical II-IIIB (AJCC/UICC 8th Edition) (stage IIIB excludes N3 disease); curative resectability has to be explicitly verified by the experienced surgical investigator.
- Confirmation by the central laboratory that the tumor harbors EGFR mutations either sensitive mutations, uncommon mutations or complex mutations.
Key exclusion criteria (16 listed)
- Patients with histologically confirmed squamous cell carcinoma, combined small cell carcinoma and large cell carcinoma.
- Molecular testing confirmed ALK translocation.
- Treatment with prior systemic cancer therapy for the current lung cancer at any time (chemotherapy, radiotherapy, target therapy, ablation, and any other local or systemic therapy).
- Patients with previous malignancies (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colorectal, endometrial, cervical, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period.
- Any active or history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications. Subjects with vitiligo, type I diabetes mellitus, resolved childhood asthma/atopy, residual hypothyroidism due to autoimmune thyroiditis only requiring hormone replacement or unexpected conditions of recurrence in the absence of an external trigger are allowed to be included.
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 |
|---|---|---|
| Toripalimab240mg IV, Q3W | Drug | Toripalimab |
Primary outcome
Major Pathological Response (MPR)
Time frame: MPR will be assessed within 2 weeks after surgery
Defined as the incidence rate in postoperative pathology where the percentage of surviving tumor cells in the tumor bed is ≤ 10%, regardless of the presence or absence of live tumor cells in the lymph nodes.
6 secondary outcomes
Pathological Complete Response (pCR)
Time frame: pCR will be assessed within 2 weeks after surgery
Objective Response Rate (ORR)
Time frame: Tumor response will be evaluated within 30 days after last dose of neoadjuvant treatment
2-year Event Free Survival (EFS)
Time frame: 2 years after the date of initiation of neoadjuvant treatment
2-year Overall Survival (OS)
Time frame: 2 years after the date of initiation of neoadjuvant treatment
Safety (Number of Participants With Grade 3 and Higher-grade Treatment-related Adverse Events)
Time frame: From date of neoadjuvant treatment until surgery was applied during study period or up to at least 90 days after last dose.
Feasibility (Number of Participants Who Finished Neoadjuvant therapy and Receive Surgery Within 3-6 Weeks After Neoadjuvant Therapies)
Time frame: 6 weeks after last dose of neoadjuvant treatment
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 18 Nov 2024.
- Individual participant dataSharing planned: No
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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.
Hecheng Li, PhD, MD principal investigator
Ruijin hospitalRuijin Hospital, Shanghai Jiao Tong University School of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Toripalimab in people with Carcinoma, Non-Small-Cell Lung, run by Ruijin Hospital at 2 sites in 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 10 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 18 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
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 Hecheng Li, PhD, MD (00862164370045, lihecheng2000@hotmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Major Pathological Response (MPR) (time frame: MPR will be assessed within 2 weeks after surgery). 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 18 Nov 2024.