Non Small Cell Lung CancerPhase 2NCT06620822
Efficacy of PD-1 Inhibitor Combination Therapy in Non-small Cell Lung Cancer Patients Who Have Not Achieved Major Pathologic Response After Neoadjuvant Immunotherapy: a Multicenter, Phase II Clinical Trial
A Phase 2 study testing IBI363, LM-108+Sintilimab and IBI310+Sintilimab in people with Non Small Cell Lung Cancer, run by Shanghai Pulmonary Hospital, Shanghai, China at 1 site in China.
Trial summary
Exploring the efficacy of PD-1 inhibitor combination therapy strategies for adjuvant therapy in a population that has not achieved major pathological regression after neoadjuvant immunotherapy for non-small cell lung cancer: a multicenter, phase II clinical study Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Non Small Cell Lung Cancer
- What is being tested?
- IBI363, LM-108+Sintilimab and IBI310+Sintilimab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 296 participants
- Where
- 1 siteChina
- Study dates
- 30 Sep 2024to 30 Sep 2027
- 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
- Subjects ≥ 18 years of age on the day of signed informed consent, male or female, and willing to follow study procedures;
- ECOG score of 0 ~ 1;
- Patients with resectable clinical stage II-IIIB (N2 only) NSCLC prior to neoadjuvant as assessed by the investigator (AJCC 8th ed.) and who are receiving 3 to 4 courses of standard PD-1 monoclonal antibody in combination with chemotherapy (platinum-containing two-agent chemotherapy) as neoadjuvant therapy during the neoadjuvant phase
- Pathological evaluation of tumor for MPR (less than 10% residual tumor cells from the primary tumor) and specific remission rate (1 - residual tumor/primary tumor)
- Subjects must have had complete resection of the NSCLC (no residual tumor and all surgical margins negative)
- Histologically or cytologically confirmed squamous or non-squamous NSCLC.
Who cannot join
- Subjects who have undergone segmental lung resection or wedge resection only, and subjects who have not undergone systemic or lobe-specific lymph node dissection;
- Postoperative treatment with off-protocol antitumor therapy (e.g., radiotherapy, chemotherapy, targeted therapy, other immunotherapies, etc.; antitumor herbal therapies require a 2-week washout period);
- Severe grade 3 or higher irAE or severe organ damage during neoadjuvant immunotherapy;
- Previous history of allogeneic bone marrow or organ transplantation;
- Previous or current interstitial pneumonitis/lung disease requiring systemic hormone therapy;
- Uncontrolled hypertension (blood pressure ≥150/90 mmHg at rest), with antihypertensive medications maintained at a stable dose for 7 days prior to the first dose of study drug;
- Combination of other malignant tumors within 5 years prior to the first dose of study drug that require active treatment, except for tumors cured in the opinion of the investigator;
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Chang Chen, MD, PhD contact
China1 site
Shanghai Pulmonary Hospital
Shanghai, Shanghai Municipality, 200433
Chang Chen, MD, PhD, +86-021-65115006 ext. 2074, chenthoracic@163.com
About this study
Exploring the efficacy of PD-1 inhibitor combination therapy strategies for adjuvant therapy in a population that has not achieved major pathological regression after neoadjuvant immunotherapy for non-small cell lung cancer: a multicenter, phase II clinical study
Read the detailed description
This study explores the potential resistance problem in patients with low response rates after neoadjuvant ICIs treatment by addressing their potential resistance problems through an adjuvant immune combination regimen of ICIs, with the aim of providing a personalized choice of perioperative regimens for patients with early stage II-III resectable NSCLC, and to reduce the risk of postoperative recurrence and death in patients.
- Conditions
- Non Small Cell Lung Cancer
- Being tested
- IBI363, LM-108+Sintilimab, IBI310+Sintilimab, Sintilimab
- 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.
IBI363Drug
IBI363 is the worlds first PD-1/IL-2α bispecific antibody fusion protein with an IL-2 arm that has been designed and modified to retain CD25 (IL-2Rɑ) activity to maximize efficacy and high selectivity, and to reduce binding to IL-2Rβγ to reduce systemic toxicity, whereas the PD-1 binding arm allows for blockade of PD-1 and selective delivery of IL-2. Therefore, IBI363 has the ability to simultaneously block the PD-1/PD-L1 pathway and activate the IL-2 pathway, which can more effectively activate tumor-specific T cells. IL-2, as an important cytokine for activating tumor-specific CD8+ T cells, is mechanistically complementary to immune checkpoint inhibitors, and can reverse T-cell depletion, thereby overcoming immune resistance.
LM-108+SintilimabDrug
LM-108 is a humanized monoclonal antibody targeting the human chemokine CC receptor 8 (CCR8) and is able to modulate the tumor microenvironment by specifically removing tumor-infiltrating regulatory T cells (Treg) through antibody-dependent cell-mediated cytotoxicity (ADCC) without affecting peripheral Treg.
IBI310+SintilimabDrug
The principle of CTLA-4 combined with PD-1 therapy is to fully relieve the inhibition of T cells by blocking both CTLA-4 and PD-1 immune checkpoints simultaneously.CTLA-4 inhibitors mainly work in the initial immune response stage by blocking the binding of CTLA-4 to B7 and enhancing the activation and proliferation of the initial T cells; whereas PD-1 inhibitors restore the anti-tumor activity of activated T cells by blocking the binding of PD-1 to its ligand PD-L1/PD-L2 and restoring their anti-tumor activity. and its ligand PD-L1/PD-L2 binding, lifting the functional inhibition of activated T cells and restoring their anti-tumor activity. Combination therapy can fully activate T-cells, improve the immune system\'s ability to recognize and attack tumors, enhance the anti-tumor immune response, and overcome the drug resistance of single therapy, thus improving the therapeutic effect.
SintilimabDrug
Sindilizumab (Sintilimab) is a humanized anti-PD-1 monoclonal antibody that has demonstrated promising anti-tumor activity in several cancer types. It works by blocking the binding of PD-1 to its ligands, PD-L1 and PD-L2, thereby lifting the inhibition of T-cells and restoring the immune system\'s killing function against tumor cells.
| Study group | Role | What they receive |
|---|---|---|
| Sintilimab | Active comparator | Not described Receives: Drug: Sintilimab |
| LM-108+Sintilimab | Experimental | Not described Receives: Drug: LM-108+Sintilimab |
| IBI310+Sintilimab | Experimental | Not described Receives: Drug: IBI310+Sintilimab |
| IBI363 | Experimental | Not described Receives: Drug: IBI363 |
What is being measured
The primary outcome is the main question the study is designed to answer.
2-year DFS rate
2-year DFS rate for Non-MPR treatment groups: DFS is defined as the time from surgery to tumor recurrence or death from any cause (whichever occurs first). 2-year DFS rate is defined as the probability of remaining free of disease recurrence or death at the 2-year time point.
Measured: 2 years
Secondary outcomes (2)
2-year OS rate
2-year OS rate in the Non-MPR treatment groups: OS is defined as the time from the start of surgery to death from any cause. 2-year OS rate is defined as the probability of remaining free of death from any cause at the 2-year time point;
Measured: 2 years
safety
Safety assessment: incidence and severity of AE (graded according to CTCAE v5.0), severity, and its relationship to the trial treatment; any laboratory tests, abnormal vital signs and physical examination findings, etc.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2024
- Study start30 Sep 2024 (estimated)
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Sep 2027 (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.
- 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
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 296 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Chang Chen, Shanghai Pulmonary Hospital, Shanghai, China
- Investigators
- Chang Chen, MD, PhD, Principal investigator, Shanghai Pulmonary Hospital, School of Medicine, Tongji University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06620822
- Sponsor's protocol ID
- STAR011
- Status last verified
- Sep 2024
- First submitted
- 28 Sep 2024
- Last updated
- 1 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- 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 1 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of PD-1 Inhibitor Combination Therapy in Non-small Cell Lung Cancer Patients Who Have Not Achieved Major Pathologic Response After Neoadjuvant Immunotherapy: a Multicenter, Phase II Clinical Trial
- ClinicalTrials.gov ID
- NCT06620822
- Acronym / sponsor ID
- STAR011
- Conditions
- Non Small Cell Lung Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 296 participants (estimated)
- Lead sponsor
- Shanghai Pulmonary Hospital, Shanghai, ChinaUniversity, hospital or other
- Study start
- 30 Sep 2024 (estimated)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Sep 2027 (estimated)
- First posted
- 1 Oct 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.
Exploring the efficacy of PD-1 inhibitor combination therapy strategies for adjuvant therapy in a population that has not achieved major pathological regression after neoadjuvant immunotherapy for non-small cell lung cancer: a multicenter, phase II clinical study
Detailed description
This study explores the potential resistance problem in patients with low response rates after neoadjuvant ICIs treatment by addressing their potential resistance problems through an adjuvant immune combination regimen of ICIs, with the aim of providing a personalized choice of perioperative regimens for patients with early stage II-III resectable NSCLC, and to reduce the risk of postoperative recurrence and death in patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Sintilimab | Active comparator | Drug: Sintilimab |
| LM-108+Sintilimab | Experimental | Drug: LM-108+Sintilimab |
| IBI310+Sintilimab | Experimental | Drug: IBI310+Sintilimab |
| IBI363 | Experimental | Drug: IBI363 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Subjects ≥ 18 years of age on the day of signed informed consent, male or female, and willing to follow study procedures;
- ECOG score of 0 ~ 1;
- Patients with resectable clinical stage II-IIIB (N2 only) NSCLC prior to neoadjuvant as assessed by the investigator (AJCC 8th ed.) and who are receiving 3 to 4 courses of standard PD-1 monoclonal antibody in combination with chemotherapy (platinum-containing two-agent chemotherapy) as neoadjuvant therapy during the neoadjuvant phase
- Pathological evaluation of tumor for MPR (less than 10% residual tumor cells from the primary tumor) and specific remission rate (1 - residual tumor/primary tumor)
- Subjects must have had complete resection of the NSCLC (no residual tumor and all surgical margins negative)
Key exclusion criteria (7 listed)
- Subjects who have undergone segmental lung resection or wedge resection only, and subjects who have not undergone systemic or lobe-specific lymph node dissection;
- Postoperative treatment with off-protocol antitumor therapy (e.g., radiotherapy, chemotherapy, targeted therapy, other immunotherapies, etc.; antitumor herbal therapies require a 2-week washout period);
- Severe grade 3 or higher irAE or severe organ damage during neoadjuvant immunotherapy;
- Previous history of allogeneic bone marrow or organ transplantation;
- Previous or current interstitial pneumonitis/lung disease requiring systemic hormone therapy;
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 |
|---|---|---|
| IBI363IBI363 is the worlds first PD-1/IL-2α bispecific antibody fusion protein with an IL-2 arm that has been designed and modified to retain CD25 (IL-2Rɑ) activity to maximize efficacy and high selectivity, and to reduce binding to IL-2Rβγ to reduce systemic toxicity, whereas the PD-1 binding arm allows for blockade of PD-1 and selective delivery of IL-2. Therefore, IBI363 has the ability to simultaneously block the PD-1/PD-L1 pathway and activate the IL-2 pathway, which can more effectively activate tumor-specific T cells. IL-2, as an important cytokine for activating tumor-specific CD8+ T cells, is mechanistically complementary to immune checkpoint inhibitors, and can reverse T-cell depletion, thereby overcoming immune resistance. | Drug | IBI363 |
| LM-108+SintilimabLM-108 is a humanized monoclonal antibody targeting the human chemokine CC receptor 8 (CCR8) and is able to modulate the tumor microenvironment by specifically removing tumor-infiltrating regulatory T cells (Treg) through antibody-dependent cell-mediated cytotoxicity (ADCC) without affecting peripheral Treg. | Drug | LM-108+Sintilimab |
| IBI310+SintilimabThe principle of CTLA-4 combined with PD-1 therapy is to fully relieve the inhibition of T cells by blocking both CTLA-4 and PD-1 immune checkpoints simultaneously.CTLA-4 inhibitors mainly work in the initial immune response stage by blocking the binding of CTLA-4 to B7 and enhancing the activation and proliferation of the initial T cells; whereas PD-1 inhibitors restore the anti-tumor activity of activated T cells by blocking the binding of PD-1 to its ligand PD-L1/PD-L2 and restoring their anti-tumor activity. and its ligand PD-L1/PD-L2 binding, lifting the functional inhibition of activated T cells and restoring their anti-tumor activity. Combination therapy can fully activate T-cells, improve the immune system\'s ability to recognize and attack tumors, enhance the anti-tumor immune response, and overcome the drug resistance of single therapy, thus improving the therapeutic effect. | Drug | IBI310+Sintilimab |
| SintilimabSindilizumab (Sintilimab) is a humanized anti-PD-1 monoclonal antibody that has demonstrated promising anti-tumor activity in several cancer types. It works by blocking the binding of PD-1 to its ligands, PD-L1 and PD-L2, thereby lifting the inhibition of T-cells and restoring the immune system\'s killing function against tumor cells. | Drug | Sintilimab |
Primary outcome
2-year DFS rate
Time frame: 2 years
2-year DFS rate for Non-MPR treatment groups: DFS is defined as the time from surgery to tumor recurrence or death from any cause (whichever occurs first). 2-year DFS rate is defined as the probability of remaining free of disease recurrence or death at the 2-year time point.
2 secondary outcomes
2-year OS rate
Time frame: 2 years
safety
Time frame: 2 years
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 1 Oct 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.
Chang Chen, MD, PhD contact
Chang Chen, MD, PhD principal investigator
Shanghai Pulmonary Hospital, School of Medicine, Tongji University
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 IBI363, LM-108+Sintilimab and IBI310+Sintilimab in people with Non Small Cell Lung Cancer, run by Shanghai Pulmonary Hospital, Shanghai, China 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 7 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 1 Oct 2024. 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 Junqi Wu (19102122052, wujq0724@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
2-year DFS rate (time frame: 2 years). 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 1 Oct 2024.