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

NCT06620822 | Not Yet Recruiting Phase 2 DMC

• 1 other identifier: STAR011
• Study Type: interventional
• Target: 296
• Locations: 1 country
• Sites: 1

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

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (2)

• 2-year OS rate

  2 years

• safety

  2 years

Study Arms (4)

Sintilimab

ACTIVE COMPARATOR

Drug: Sintilimab

LM-108+Sintilimab

EXPERIMENTAL

Drug: LM-108+Sintilimab

IBI310+Sintilimab

EXPERIMENTAL

Drug: IBI310+Sintilimab

IBI363

EXPERIMENTAL

Drug: IBI363

Interventions

IBI363 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.

IBI363

LM-108+Sintilimab 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.

LM-108+Sintilimab

IBI310+Sintilimab 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.

IBI310+Sintilimab

Sintilimab 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.

Sintilimab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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;

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

sintilimab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Chang Chen, MD, PhD

  Shanghai Pulmonary Hospital, School of Medicine, Tongji University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Junqi Wu

CONTACT

19102122052; wujq0724@163.com

Chang Chen, MD, PhD

CONTACT

chenthoracic@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: 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

Study Record Dates

• First Submitted: September 28, 2024
• First Posted: October 1, 2024
• Study Start: September 30, 2024
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2027
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)