Anti-PD-1 and VEGF Bispecific Antibody AK112 in Combination With Chemotherapy in Patients With ES-SCLC

NCT ID: NCT05116007

Last Updated: 2024-05-31

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 35 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-29
• Study Completion Date: 2023-12-04

Brief Summary

Phase Ib open label, multicenter study to evaluate the efficacy and safety of anti-PD-1 and VEGF bispecific antibody (AK112) combined with chemotherapy in patients with ES-SCLC.

Detailed Description

Small cell lung cancer (SCLC) is an aggressive type of neuroendocrine tumor with the majority of patients (about 60-70%) being diagnosed with metastatic disease and with a median survival ranging from 7 to 12 months. Combination chemotherapy , namely a platinum and etoposide-based regimen, represents the cornerstone of treatment for extensive stage SCLC(ES-SCLC). Despite this the duration of response is short and nearly all patients develop disease relapse or progression. The recent approval of atezolizumab in combination with carboplatin and etoposide as first line in patients with ES- SCLC is surely a step forward in the understanding the molecular landscape and treatment of this complex tumor, but new therapeutic approaches need to be explored.This trial aims to assess the safety and efficacy of a new therapeutic strategy that combines to carboplatin and etoposide, and a new drug AK112.The treatment will start with an induction phase during which eligible patients will receive, by intravenous way, a combination of the above mentioned drugs according to a specific administration regimen. This phase will last about 12 weeks. Thereafter the treatment will proceed with a maintenence phase lasting for a maximum of 24 months during which the patients will receive only AK112, by intravenous way. Treatment will be discontnued in case of until the toxicity became intolerable, the investigator determined that there was no further clinical benefit (based on a combination of RECIST V1.1 imaging assessment and clinical status), 24 months of treatment was completed, or the study was withdrawn for other reasons. During the study period the patients will undergo to periodic visits and laboratory, radiologic assessments to monitor the efficacy and the safety of the ongoing treatment.

Conditions

SCLC, Extensive Stage

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Experimental

Subjects receive AK112 plus Etoposide and Carboplatin every 3- week cycle (Q3W) for 4 cycles followed by AK112 until progression.

Group Type: EXPERIMENTAL

AK112

Intervention Type: DRUG

IV infusion

Etoposide

Intervention Type: DRUG

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Carboplatin

Intervention Type: DRUG

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4)

Interventions

AK112

IV infusion

Intervention Type: DRUG

Etoposide

Etoposide intravenous infusion was administered at a dose of 100 mg/m\^2 on Days 1, 2, and 3 of each 21-day cycle during the induction phase (Cycles 1-4).

Intervention Type: DRUG

Carboplatin

Carboplatin intravenous infusion to achieve an initial target AUC of 5 mg/mL/min was administered on Day 1 of each 21-day cycle during the induction phase (Cycles 1-4)

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 18 to 75 years old (at the time of inform consent obtained).
• Be able and willing to provide written informed consent and to comply with all requirements of study participation (including all study procedures).
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration Lung Study Group [VALG] staging system).
• Be able to provide formalin fixed, paraffin-embedded (FFPE) tumor tissue obtained from either a core or excisional tumor biopsy.
• Have a life expectancy of at least 3 months.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 assessed by investigator
• Has adequate organ function
• All female and male subjects of reproductive potential must agree to use an effective method of contraception, as determined by the Investigator, during and for 120 days after the last dose of study treatment.

Exclusion Criteria

• Undergone major surgery within 30 days prior to the first dose of study treatment
• History of prior malignancy except that basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer
• Active central nervous system (CNS) metastases
• History of active autoimmune disease that has required systemic treatment in the past 2 years (i.e.,corticosteroids or immunosuppressive drugs).
• Active infection requiring systemic therapy
• Active Hepatitis B or Hepatitis C
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
• Pregnant or lactating women

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Akeso

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shun Lu, Professor

Role: PRINCIPAL_INVESTIGATOR

Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiaotong University, P. R. China

Locations

Shun Lu

Shanghai, Shanghai Municipality, China

Countries

China

Other Identifiers

AK112-103

Identifier Type: -

Identifier Source: org_study_id