Non-Small Cell Lung CancerPhase 2NCT05800340
Neoadjuvant Immunotherapy in Rare Mutations Localized NSCLC
A Phase 2 study testing Toripalimab, Nab paclitaxel and Pemetrexed in people with Non-Small Cell Lung Cancer and RET Driver Mutation, run by Guangdong Provincial People's Hospital at 1 site in China.
Trial summary
Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Toripalimab plus chemotherapy in rare mutations stage IIB-IIIB NSCLC followed by optional adjuvant treatment upon investigators' decisions. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non-Small Cell Lung Cancer, RET Driver Mutation, BRAF V600 Mutation
- What is being tested?
- Toripalimab, Nab paclitaxel and Pemetrexed
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 4 Apr 2023to 31 Dec 2026
- 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
- Age: 18 Years and older
- ECOG physical score 0-1 points; expected survival time ≥ 3 months;
- Pathologically confirmed diagnosis with Stage IIB-IIIB NSCLC which harbored rare driver alteration including RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;
- Lung function capacity capable of tolerating the proposed lung surgery
- Available tissue of tumor for PD-L1 test
- Subjects voluntarily joined the study and signed informed consent, with good compliance to follow-up.
Who cannot join
- Stage I and stage IV NSCLC;
- Patients who have previously used any other anti-tumor drugs or radiotherapy;
- Large panel NGS indicated sensitive EGFR alteration, ALK fusion, ROS1 fusion or any other driver mutations combined with MDM2/MDM4 amplification;
- Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
- A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
- Patients with any underlying disease that investigators consider it may affect patient's prognosis including sever cardiovascular, pulmonary disease or serious infections; Clinically obvious gastrointestinal abnormalities, which may affect the intake, transport or absorption of drugs (such as inability to swallow, chronic diarrhea, intestinal obstruction, etc.), or patients with total gastrectomy;
Show all 12Show fewer
- Known or suspected autoimmune disease with activity. Participants may be enrolled if they have type 1 diabetes, hypothyroidism that requires only hormone replacement therapy, skin diseases that require no systemic treatment (such as purpura, psoriasis, or hair loss), or other conditions that are not expected to return without external trigger.
- Patients with active hepatitis B (positive for HBsAg) or hepatitis C (positive for HCV RNA).
- Patients with human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)
- Patients with other active malignancies within five years
- Pregnant or lactating women; those who have fertility are unwilling or unable to take effective contraceptive measures;
- Patients with low compliance or willingness to take the drugs and surveillance.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
Guanzhou, Guangdong, 510080
Wen-Zhao Zhong, Ph.D, +86 02083827812, syzhongwenzhao@scut.edu.cn
Rui Fu, Ph.D, +86 02083827812, ruifu66@foxmail.com
About this study
Official title: Neoadjuvant Toripalimab Combined With Chemotherapy in Rare Mutations Stage IIB-IIIB NSCLC
Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Toripalimab plus chemotherapy in rare mutations stage IIB-IIIB NSCLC followed by optional adjuvant treatment upon investigators' decisions.
Read the detailed description
30 eligible patients will be enrolled and 3 cycles of Toripalimab 240mg + chemotherapy (Nab-paclitaxel + carboplatin, or pemetrexed + carboplatin) will be administered. Rare mutations include RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including chemotherapy or/and rare mutations TKI upon investigators' consideration. The primary objective of the study is pathological complete response (pCR) defined as no residue tumor found in both primary lung cancer and metastatic lymph nodes.
- Conditions
- Non-Small Cell Lung Cancer, RET Driver Mutation, BRAF V600 Mutation, Erb-B2 Receptor Tyrosine Kinase Exon 20 Mutation, MET Amplification, MET Exon 14 Skipping Mutation
- Being tested
- Toripalimab, Nab paclitaxel, Pemetrexed, Carboplatin
- Keywords
- Non-small Cell Lung Cancer, Neoadjuvant immunotherapy, Rare Mutations
- 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.
ToripalimabBiological
240mg Q3W
Nab paclitaxelDrug
135 mg/m2, d1, 8 Q3W
PemetrexedDrug
500mg/m2, d1 Q3W
CarboplatinDrug
AUC 5, d1 Q3W
| Study group | Role | What they receive |
|---|---|---|
| Toripalimab plus chemotherapy | Experimental | 3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 years or till disease progression or unacceptable toxicity. Receives: Biological: Toripalimab; Drug: Nab paclitaxel; Drug: Pemetrexed; Drug: Carboplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological Complete Response (pCR)
Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.
Measured: pCR will be assessed within 2 weeks after surgery
Secondary outcomes (4)
Major Pathological Response (MPR)
Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for both primary lung lesions and metastatic lymph nodes.
Measured: MPR will be assessed within 2 weeks after surgery
Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the length of time from initiation of neoadjuvant treatment 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.
Measured: From date of initiation of neoadjuvant treatment to disease progression, reoccurrence, or death due to any cause, up to 36 months.
Overall Survival (OS)
Overall survival (OS) is defined as the time between the date of initiation of neoadjuvant treatment and the date of death.
Measured: From date of initiation of neoadjuvant treatment to the date of all-cause death, assessed up to 60 months.
Adverse Events (AEs)
Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment or surgery.
Measured: From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2023
- Study start4 Apr 2023
- Primary completion31 Dec 2024 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-Small Cell Lung CancerStudies of the same condition, open and under way.
- 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
- 3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 year or till disease progression or unacceptable toxicity.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Guangdong Provincial People's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05800340
- Sponsor's protocol ID
- NEORM
- Status last verified
- Mar 2023
- First submitted
- 21 Mar 2023
- Last updated
- 5 Apr 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neoadjuvant Toripalimab Combined With Chemotherapy in Rare Mutations Stage IIB-IIIB NSCLC
- ClinicalTrials.gov ID
- NCT05800340
- Acronym / sponsor ID
- NEORM
- Conditions
- Non-Small Cell Lung Cancer, RET Driver Mutation, BRAF V600 Mutation, Erb-B2 Receptor Tyrosine Kinase Exon 20 Mutation, MET Amplification, MET Exon 14 Skipping Mutation
- Keywords
- Non-small Cell Lung Cancer, Neoadjuvant immunotherapy, Rare Mutations
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Guangdong Provincial People's HospitalUniversity, hospital or other
- Collaborators
- Shanghai Junshi Bioscience Co., Ltd.
- Study start
- 4 Apr 2023 (actual)
- Primary completion
- 31 Dec 2024 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 5 Apr 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.
Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Toripalimab plus chemotherapy in rare mutations stage IIB-IIIB NSCLC followed by optional adjuvant treatment upon investigators' decisions.
Detailed description
30 eligible patients will be enrolled and 3 cycles of Toripalimab 240mg + chemotherapy (Nab-paclitaxel + carboplatin, or pemetrexed + carboplatin) will be administered. Rare mutations include RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including chemotherapy or/and rare mutations TKI upon investigators' consideration. The primary objective of the study is pathological complete response (pCR) defined as no residue tumor found in both primary lung cancer and metastatic lymph nodes.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 year or till disease progression or unacceptable toxicity.
| Arm | Type | Receives |
|---|---|---|
| Toripalimab plus chemotherapy | Experimental | Biological: Toripalimab, Drug: Nab paclitaxel, Drug: Pemetrexed, Drug: Carboplatin3 cycles of neoadjuvant Toripalimab (240mg every 3 weeks) with nab-paclitaxel + carboplatin, or pemetrexed + carboplatin (decided by investigators; nab-paclitaxel 135 mg/m2, d1, 8 and carboplatin AUC 5, d1 every 3 weeks; pemetrexed, 500mg/m2 d1 every 3 weeks) will be administered before surgery, followed by optional adjuvant treatment including chemotherapy for 3-4 cycles or rare mutations-TKIs for up to 2 years or till disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age: 18 Years and older
- ECOG physical score 0-1 points; expected survival time ≥ 3 months;
- Pathologically confirmed diagnosis with Stage IIB-IIIB NSCLC which harbored rare driver alteration including RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Suspected N2 disease should be confirmed by either mediastinoscopy or EBUS. N1 disease could be determined through PET/CT but biopsy of primary lung cancer is needed;
- Lung function capacity capable of tolerating the proposed lung surgery
- Available tissue of tumor for PD-L1 test
Key exclusion criteria (12 listed)
- Stage I and stage IV NSCLC;
- Patients who have previously used any other anti-tumor drugs or radiotherapy;
- Large panel NGS indicated sensitive EGFR alteration, ALK fusion, ROS1 fusion or any other driver mutations combined with MDM2/MDM4 amplification;
- Histologically confirmed small cell lung cancer (including lung cancer mixed with small cell lung cancer and non-small cell lung cancer);
- A history of active bleeding within the 6 months before enrollment, or receiving thrombolysis or anticoagulant therapy, or the investigator believes that there is a clear tendency to gastrointestinal bleeding (such as esophageal varices with bleeding risk, local activity) Ulcer lesions, etc.) or active hemoptysis;
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 Q3W | Biological | Toripalimab plus chemotherapy |
| Nab paclitaxel135 mg/m2, d1, 8 Q3W | Drug | Toripalimab plus chemotherapy |
| Pemetrexed500mg/m2, d1 Q3W | Drug | Toripalimab plus chemotherapy |
| CarboplatinAUC 5, d1 Q3W | Drug | Toripalimab plus chemotherapy |
Primary outcome
Pathological Complete Response (pCR)
Time frame: pCR will be assessed within 2 weeks after surgery
Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.
4 secondary outcomes
Major Pathological Response (MPR)
Time frame: MPR will be assessed within 2 weeks after surgery
Event-Free Survival (EFS)
Time frame: From date of initiation of neoadjuvant treatment to disease progression, reoccurrence, or death due to any cause, up to 36 months.
Overall Survival (OS)
Time frame: From date of initiation of neoadjuvant treatment to the date of all-cause death, assessed up to 60 months.
Adverse Events (AEs)
Time frame: From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.
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 5 Apr 2023.
Related trials for Non-Small Cell Lung Cancer
RecruitingPhase 1/2
KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of Pembrolizumab (MK-3475) With or Without Chemotherapy When Used With Investigational Agents in Treatment-naïve Participants With Stage IV Non-small Cell Lung Cancer (NSCLC) (MK-3475-01A/KEYMAKER-U01A)
Carcinoma, Non-Small-Cell Lung
RecruitingObservational study
KEYMAKER-U01 Umbrella Master Study: Studies of Investigational Agents With Either Pembrolizumab (MK-3475) Alone or With Pembrolizumab PLUS Chemotherapy in Participants With Non-small Cell Lung Cancer (NSCLC) (MK-3475-U01/KEYMAKER-U01)
Carcinoma, Non-Small-Cell Lung
RecruitingPhase 3
Testing the Addition of a Type of Drug Called Immunotherapy to the Usual Chemotherapy Treatment for Non-small Cell Lung Cancer, an ALCHEMIST Treatment Trial (Chemo-IO [ACCIO])
Lung Non-Small Cell Carcinoma, Lung Non-Small Cell Squamous Carcinoma
Active, not recruitingPhase 3
A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions
Carcinoma, Non-Small-Cell Lung
RecruitingPhase 3
A Study to Assess Disease Activity and Adverse Events of Intravenous (IV) Telisotuzumab Vedotin Compared to IV Docetaxel in Adult Participants With Previously Treated Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Non Small Cell Lung Cancer, c-MET
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.
1 site 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, Nab paclitaxel and Pemetrexed in people with Non-Small Cell Lung Cancer and RET Driver Mutation, run by Guangdong Provincial People's Hospital at 1 site 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 6 inclusion and 12 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 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 Wen-Zhao Zhong, Ph.D (+86 02083827812, syzhongwenzhao@scut.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pathological Complete Response (pCR) (time frame: pCR 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 5 Apr 2023; AzTrials last refreshed its copy on 30 Oct 2026.