A Trial of AK112 (PD1/VEGF Bispecific) in Combination With Chemotherapy in Patients With NSCLC

NCT04736823 | Active Not Recruiting Phase 2

• 1 other identifier: AK112-201
• Study Type: interventional
• Target: 265
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase II study. All patients are stage IIIB/C or IV non-small cell lung cancer(NSCLC), Eastern Cooperative Oncology Group (ECOG) performance status 0-1. The purpose of this study is to evaluate the efficacy and safety of AK112 in combination with chemotherapy in patients with NSCLC.

Conditions

NSCLC

Outcome Measures

Primary Outcomes (1)

• ORR

  ORR is the proportion of subjects with CR or PR , based on RECIST v1.1.

  Up to approximately 2 years

Secondary Outcomes (3)

• PFS

  Up to approximately 2 years

• OS

  Up to approximately 2 years

• Disease control rate

  Up to approximately 2 years

Study Arms (7)

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin)

EXPERIMENTAL

non-Squamous NSCLC:Subjects receive AK112 plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK112 plus Pemetrexed until progression. Squamous NSCLC:Subjects receive AK112 plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK112 until progression.

Drug: AK112; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin

Part1 Cohort2(AK112 + Pemetrexed +Carboplatin)

EXPERIMENTAL

Subjects receive AK112 plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK112 plus Pemetrexed until progression.

Drug: AK112; Drug: Pemetrexed; Drug: Carboplatin

Part1 Cohort3(AK112 + Docetaxel)

EXPERIMENTAL

Subjects receive AK112 plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.

Drug: AK112; Drug: Docetaxel

Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin)

EXPERIMENTAL

non-Squamous NSCLC:Subjects receive AK112 plus Pemetrexed and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK112 plus Pemetrexed until progression. Squamous NSCLC:Subjects receive AK112 plus Paclitaxel and Carboplatin on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by AK112 until progression.

Drug: AK112; Drug: Pemetrexed; Drug: Paclitaxel; Drug: Carboplatin

Part3 group A(AK112 + Docetaxel)

EXPERIMENTAL

Subjects receive AK112 plus Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.

Drug: AK112; Drug: Docetaxel

Part3 group B(AK112)

EXPERIMENTAL

Subjects receive AK112 on Day 1 of every 3-week cycle (Q3W) until progression.

Drug: AK112

Part3 group C(Docetaxel)

EXPERIMENTAL

Subjects receive Docetaxel on Day 1 of every 3-week cycle (Q3W) until progression.

Drug: Docetaxel

Interventions

AK112 DRUG

IV infusion

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin); Part1 Cohort2(AK112 + Pemetrexed +Carboplatin); Part1 Cohort3(AK112 + Docetaxel); Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin); Part3 group A(AK112 + Docetaxel); Part3 group B(AK112)

Pemetrexed DRUG

IV infusion

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin); Part1 Cohort2(AK112 + Pemetrexed +Carboplatin); Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin)

Paclitaxel DRUG

IV infusion

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin); Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin)

Carboplatin DRUG

IV infusion

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin); Part1 Cohort2(AK112 + Pemetrexed +Carboplatin); Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin)

Docetaxel DRUG

IV infusion

Part1 Cohort3(AK112 + Docetaxel); Part3 group A(AK112 + Docetaxel); Part3 group C(Docetaxel)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).
• Have histologically- or cytologically-confirmed diagnosis of Stage IIIB/C or IV NSCLC.
• 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.

You may not qualify if:

• Is currently participating in a study of an investigational agent or using an investigational device;
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy within 2 years prior to the first dose of study treatment;
• Has undergone major surgery within 30 days prior to the first dose of study treatment;
• Has a known 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
• Has known active central nervous system (CNS) metastases;
• Has carcinomatous meningitis
• Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment NOTE: Subjects with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Subjects that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study;
• Has an active infection requiring systemic therapy;
• Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected);
• History of myocardial infarction, unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 12 months prior to day 1 of study treatment;
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of this subject to participate, in the opinion of the treating investigator;
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the study
• Has received a live virus vaccine within 30 days prior to first dose of study treatment
• Is pregnant, breastfeeding, or expecting to conceive or father a child within the projected duration of the study including 120 days following the last dose of study treatment.

Sponsors & Collaborators

• Akeso: lead

Study Sites (1)

Sun Yat-Sen University Cancer Center

Guanzhou, Guangdong, China

Location

Related Publications (1)

• Zhao Y, Chen G, Chen J, Zhuang L, Du Y, Yu Q, Zhuang W, Zhao Y, Zhou M, Zhang W, Zhang Y, Wan Y, Li W, Song W, Wang ZM, Li B, Xia M, Yang Y, Fang W, Huang Y, Zhang L. AK112, a novel PD-1/VEGF bispecific antibody, in combination with chemotherapy in patients with advanced non-small cell lung cancer (NSCLC): an open-label, multicenter, phase II trial. EClinicalMedicine. 2023 Aug 3;62:102106. doi: 10.1016/j.eclinm.2023.102106. eCollection 2023 Aug.

  PMID: 37593227 DERIVED

MeSH Terms

Interventions

Pemetrexed; Paclitaxel; Carboplatin; Docetaxel

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes

Study Officials

• Li Zhang, MD

  Sun Yat-Sen University Cancer Center

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 30, 2021
• First Posted: February 3, 2021
• Study Start: February 1, 2021
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Locations

CN (1)