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

NCT ID: NCT06620822

Last Updated: 2024-10-01

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 296 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-09-30
• Study Completion Date: 2027-09-30

Brief 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

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sintilimab

Group Type: ACTIVE_COMPARATOR

Sintilimab

Intervention Type: DRUG

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.

LM-108+Sintilimab

Group Type: EXPERIMENTAL

LM-108+Sintilimab

Intervention Type: DRUG

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+Sintilimab

Group Type: EXPERIMENTAL

IBI310+Sintilimab

Intervention Type: DRUG

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.

IBI363

Group Type: EXPERIMENTAL

IBI363

Intervention Type: DRUG

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.

Interventions

IBI363

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.

Intervention Type: DRUG

LM-108+Sintilimab

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.

Intervention Type: DRUG

IBI310+Sintilimab

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.

Intervention Type: DRUG

Sintilimab

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Subjects ≥ 18 years of age on the day of signed informed consent, male or female, and willing to follow study procedures;

2. ECOG score of 0 ~ 1;

3. 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

4. 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)

5. Subjects must have had complete resection of the NSCLC (no residual tumor and all surgical margins negative)

6. Histologically or cytologically confirmed squamous or non-squamous NSCLC.

Exclusion Criteria

1. Subjects who have undergone segmental lung resection or wedge resection only, and subjects who have not undergone systemic or lobe-specific lymph node dissection;

2. 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);

3. Severe grade 3 or higher irAE or severe organ damage during neoadjuvant immunotherapy;

4. Previous history of allogeneic bone marrow or organ transplantation;

5. Previous or current interstitial pneumonitis/lung disease requiring systemic hormone therapy;

6. 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;

7. 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;

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Shanghai Pulmonary Hospital, Shanghai, China

OTHER

Sponsor Role: lead

Responsible Party

Chang Chen

Deputy Director of MD. PhD. Program in Thoracic Surgery, Secretary of the party committee of Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Chang Chen, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Shanghai Pulmonary Hospital, School of Medicine, Tongji University

Locations

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, China

Countries

China

Central Contacts

Junqi Wu

Role: CONTACT

wujq0724@163.com

19102122052

Chang Chen, MD, PhD

Role: CONTACT

chenthoracic@163.com

Facility Contacts

Chang Chen, MD, PhD

Role: primary

chenthoracic@163.com

+86-021-65115006 ext. 2074

Other Identifiers

STAR011

Identifier Type: -

Identifier Source: org_study_id