AK112 Plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC (Apple)

Efficay and Satety of PD-1/VEGR Bispecific Antibodies (AK112) Plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC: A Multiple Centers, Multiple Cohorts, Dose Escalation Phase II Apple Study

The investigators want to evaluated the Efficay and Satety of PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC who Failed from First-Line Standard Treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Efficacy
• Intervention / Treatment: Drug: PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy

Detailed Description

The investigators want to evaluated the Efficay and Satety of PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC who Failed from First-Line Standard Treatment.

This study will be devided into three cohorts. Cohort A for EGFR mutation NSCLC, Patient with NGS idenfied EGFR sensitive mutation NSCLC who failed from first line Osimertinib will be included. The 3+3 stud will conducted for dose escalation for AK112 （from 20mg to 30mg), and than the fix dose will be set up for cohort A, B and C.

Cohort B for ALK fusion NSCLC, Patient with NGS idenfied ALK fusion NSCLC who failed from first line Alectinib will be included. All the patients will be devided two group,3'ALK and 3'ALK with reteintion of 5'ALK. All the patients will be treated with PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.

Cohort C for ROS1 fusion NSCLC, Patient with NGS idenfied ROS1 fusion NSCLC who failed from first line crizotinib or Entrectinib will be included. All the patients will be treated with PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.

The investigators will collect the satety and efficacy data for all the patients.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Yongchang Zhang; Phone Number: +8613873123436; Email: zhangyongchang@csu.edu.cn
• Study Contact Backup: Name: Liang Zeng; Phone Number: 15974139200; Email: 530490930@qq.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Eligible subjects selected for this study must meet all of the following criteria:

  1. Sign written informed consent before implementing any trial-related procedures;
  2. Age ≥18 years old and ≤75 years old;
  3. No limit on the gender;
  4. The ECOG score is 0 or 1.
• The investigators want to evaluated the Efficay and Satety of PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy for EGFR/ALK/ROS1 Positve NSCLC who Failed from First-Line Standard Treatment.

This study will be devided into three cohorts.

• Cohort A for EGFR mutation NSCLC, Patient with NGS idenfied EGFR sensitive mutation NSCLC who failed from first line Osimertinib will be included. The 3+3 stud will conducted for dose escalation for AK112 （from 20mg to 30mg), and than the fix dose will be set up for cohort A, B and C.
• Cohort B for ALK fusion NSCLC, Patient with NGS idenfied ALK fusion NSCLC who failed from first line Alectinib will be included. All the patients will be devided two group,3'ALK and 3'ALK with reteintion of 5'ALK. All the patients will be treated with PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.
• Cohort C for ROS1 fusion NSCLC, Patient with NGS idenfied ROS1 fusion NSCLC who failed from first line crizotinib or Entrectinib will be included. All the patients will be treated with PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.

The investigators will collect the satety and efficacy data for all the patients.

Exclusion Criteria:

• Histological or cytological pathology confirmed the presence of a small cell carcinoma component, or a squamous cell carcinoma as a major component
• Patients who have received immunotherapy previously, including immune checkpoint inhibitors (such as anti-PD-1/L1, anti-CTLA-4 , anti-LAG-3, etc.), immune checkpoint activators (such as ICOS, CD40, CD137, GITR, OX40 antibodies, etc.), immune cell therapy and any other treatment targeting the immunity mechanism.
• Previously received other anti-tumor therapy for advanced stages of NSCLC (stages IIIB to IV) (including cytotoxic chemotherapy used with radiotherapy, systemic chemotherapy, and anti-VEGFR therapy) .

Patients who have previously undergone adjuvant/neoadjuvant chemotherapy with the aim of curing non-metastatic diseases are eligible for inclusion in this study if disease progression occurs at least 6 months after the completion of the last chemotherapy cycle.

• Concurrent enrollment in another clinical trial is allowed, unless it involves a non-interventional clinical study or the follow-up period of an interventional study (defined as the time elapsed from the initiation of the first drug to at least 4 weeks after the last drug administration in the previous clinical study or beyond 5 half-lives of the investigational drug in that study, whichever is shorter).
• Received TKI treatment within the 2 weeks preceding the first dose; underwent palliative local therapy for non-target lesions within the 2 weeks preceding the first dose; received non-specific immunomodulatory therapy within the 2 weeks preceding the first dose, such as interleukins, interferons, thymosin alpha-1, tumor necrosis factor, etc. (excluding IL-11 used for treating thrombocytopenia); received herbal medicine or traditional Chinese medicine with anti-tumor indications within the 1 week preceding the first dose.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort of EGFR Sensitve Mutant NSCLC; Efficay, Satety and Dose Escalation of AK112 plus Platinum-based Chemotherapy for EGFR Sensitive mutant NSCLC who Failed from First-Line Osimertinib.	Drug: PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy; PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.
Experimental: Cohort of ALK Fusion NSCLC; Efficay and Satety of PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy for ALK fusion NSCLC who Failed from First-Line Osimertinib.	Drug: PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy; PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.
Experimental: Cohort of ROS1 Fusion NSCLC; Efficay and Satety of PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy for ROS1 fusion NSCLC who Failed from First-Line Crizotinib.	Drug: PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy; PD-1/VEGR bispecific antibodies (AK112) plus Platinum-based Chemotherapy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	Overall response rate	12 months
RP2D	We want to evaluate the best dose for treatment.	2 months
PFS	Progression free survival time	12 months

Collaborators and Investigators

• Sponsor: Hunan Province Tumor Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2024
• Primary Completion (Estimated): March 1, 2026
• Study Completion (Estimated): February 1, 2027

Study Registration Dates

• First Submitted: December 25, 2023
• First Submitted That Met QC Criteria: December 25, 2023
• First Posted (Actual): January 9, 2024

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Antibodies; Antibodies, Bispecific
• Other Study ID Numbers: HCH20231225

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No