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

Akeso

Status and phase: Enrolling; Phase 2

Conditions: NSCLC

Treatments: Drug: Carboplatin; Drug: Pemetrexed; Drug: AK112; Drug: Paclitaxel; Drug: Docetaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04736823

AK112-201

Details and patient eligibility

About

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.

Enrollment: 296 estimated patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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).
• 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.

Exclusion criteria

• 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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296 participants in 7 patient groups

Part1 Cohort1(AK112 + Pemetrexed or Paclitaxel+Carboplatin)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: AK112

Drug: Pemetrexed

Drug: Carboplatin

Part1 Cohort2(AK112 + Pemetrexed +Carboplatin)

Experimental group

Description:

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.

Treatment:

Drug: AK112

Drug: Pemetrexed

Drug: Carboplatin

Part1 Cohort3(AK112 + Docetaxel)

Experimental group

Description:

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

Treatment:

Drug: Docetaxel

Drug: AK112

Part2 (AK112 + Pemetrexed or Paclitaxel+Carboplatin)

Experimental group

Description:

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.

Treatment:

Drug: Paclitaxel

Drug: AK112

Drug: Pemetrexed

Drug: Carboplatin

Part3 group A(AK112 + Docetaxel)

Experimental group

Description:

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

Treatment:

Drug: Docetaxel

Drug: AK112

Part3 group B(AK112)

Experimental group

Description:

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

Treatment:

Drug: AK112

Part3 group C(Docetaxel)

Experimental group

Description:

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

Treatment:

Drug: Docetaxel