AK104 Monotherapy as Neoadjuvant and Adjuvant Therapy for Resectable Non-small Cell Lung Cancer

Study Overview
=================
Brief Summary
-----------------
AK104, a tetravalent bispecific antibody targeting PD-1 and CTLA-4, is designed to retain the efficacy benefit of combination of PD-1 and CTLA-4 and improve on the safety profile of the combination therapy. The aim of this study is to evaluate the efficacy and safety of AK104 monotherapy as neoadjuvant and adjuvant therapy for patients with resectable stage II-IIIA NSCLC.

Official Title
-----------------
An Open-label, Single-center, Phase II Study of AK104 Monotherapy as Neoadjuvant and Adjuvant Therapy for Resectable Non-small Cell Lung Cancer

Conditions
-----------------
Non-small Cell Lung Cancer

Intervention / Treatment
-----------------
* Drug: AK104


Participation Criteria
=================
Eligibility Criteria
-----------------
Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. Have previously untreated and pathologically confirmed resectable Stage II-IIIA NSCLC. Have at least one measurable lesion per RECIST 1.1 assessed by investigator. Have adequate organ function. Key Exclusion Criteria: Mixed NSCLC and small cell lung cancer histology. Patients with other active malignancies within 3 years prior to enrollment. Known active autoimmune diseases. Use of immunosuppressive agents within 14 days prior to the first dose of study treatment. Presence of other uncontrolled serious medical conditions.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AK104<br>Participants receive two cycles of AK104 as neoadjuvant therapy prior to surgery; followed by surgery; followed by standard adjuvant chemotherapy +/- radiotherapy per investigator; followed by adjuvant AK104 for 6 months. | Drug: AK104<br>* 10 mg/kg via intravenous infusion on Day 1 of each 21-day cycle.<br>* Other names: Cadonilimab;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major Pathological Response (MPR) Rate | defined as the percentage of participants having ≤10% viable tumor cells in the resected primary tumor and all resected lymph nodes following completion of neoadjuvant therapy. | After surgery (approximately 7 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pathological Complete Response (pCR) Rate | defined as the percentage of participants having an absence of residual invasive cancer in resected lung specimens and lymph nodes following completion of neoadjuvant therapy. | After surgery (approximately 7 weeks) | 
| Incidence of Surgical Complications | defined as ≥ grade 3 or severe intraoperative and perioperative complications. | Up to approximately 30 days following surgery | 
| Complete (R0) Resection Rate | defined as the percentage of participants achieving complete surgical resection following completion of neoadjuvant therapy. | After surgery (approximately 7 weeks) | 
| Objective Response Rate (ORR) | defined as the percentage of participants having complete response or partial response to protocol treatment. Objective response will be measured by RECIST 1.1. | At the end of 2 cycles of neoadjuvant therapy (each cycle is 21 days) | 
| Event Free Survival (EFS) | defined as the time from the first dose of study drug to disease progression per RECIST 1.1 that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first. | Up to approximately 5 years | 
| Adverse Events (AEs) |  | From the first dose of neoadjuvant treatment until 90 days after the last dose of adjuvant treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
neoadjuvant and adjuvant therapy, bispecific antibody