A Study of HLX10 in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04 Compared With Carboplatin+Pemetrexed in 1L Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Henlius Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Non-Small-Cell Lung; Carcinoma

Treatments: Drug: HLX04, a bevacizumab biosimilar; Drug: Carboplatin; Drug: Pemetrexed; Drug: HLX10, an engineered anti-PD-1 antibody

Study type: Interventional

Funder types: Industry

Identifiers

NCT03952403

HLX10-002-NSCLC301

Details and patient eligibility

About

This study involves a two-part design. Part 1 is designed to evaluate the safety and tolerability of the 4 drug (HLX10+HLX04+carboplatin+pemetrexed). Part 2 is a randomized, open-label study, which will evaluate the safety and efficacy of HLX10 in combination with carboplatin+pemetrexed with or without HLX04(biosimilar of avastin) compared with treatment with carboplatin+pemetrexed in 1st line Stage IIIB/IIIC or IV non-squamous NSCLC. Participants will be randomized in a 1:1:1 ratio to Arm A (HLX10+HLX04+Carboplatin+Pemetrexed), Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed), or Arm C (HLX10 placebo + HLX04 placebo+Carboplatin+Pemetrexed).

Enrollment: 643 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Histologically or cytologically confirmed, Stage IIIB/IIIC or IV non-squamous NSCLC
2. Participants with no EGFR, ALK and ROS1 mutation.
3. Participants with no prior treatment for Stage IIIB/IIIC or IV non-squamous NSCLC
4. Measurable disease as defined by RECIST v1.1
5. Eastern Cooperative Oncology Group performance status 0 or 1
6. Adequate hematologic and end organ function

Exclusion criteria

1. Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
2. Active central nervous system metastases
3. Prior treatment with cluster of differentiation immune checkpoint blockade therapies or Bevacizumab
4. Has received a surgical operation within 4 weeks from the initial drug administration
5. Active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.
6. Currently having or have had interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity
7. Any active infection requiring systemic anti-infective therapy within 14 days prior to study drug administration
8. Uncontrollable active infection(s)
9. History of immunodeficiency, including HIV antibody positive
10. active hepatitis B; or hepatitis C virus infections
11. Has bleeding tendency
12. History of severe cardiovascular diseases
13. Known gastrointestinal diseases as follows, Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or > moderate esophageal varices
14. Pregnant or breastfeeding female

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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643 participants in 4 patient groups

Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)

Experimental group

Description:

Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Treatment:

Drug: HLX04, a bevacizumab biosimilar

Drug: HLX10, an engineered anti-PD-1 antibody

Drug: Carboplatin

Drug: Pemetrexed

Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)

Experimental group

Description:

Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Treatment:

Drug: HLX04, a bevacizumab biosimilar

Drug: HLX10, an engineered anti-PD-1 antibody

Drug: Carboplatin

Drug: Pemetrexed

Part 2-Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed)

Experimental group

Description:

Participants will receive IV infusion of HLX10 and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Treatment:

Drug: HLX10, an engineered anti-PD-1 antibody

Drug: Carboplatin

Drug: Pemetrexed

Part 2-Arm C (HLX10 placebo+HLX04 placebo+Carboplatin+Pemetrexed)

Active Comparator group

Description:

Participants will receive IV infusion of HLX10 placebo and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.

Treatment:

Drug: Carboplatin

Drug: Pemetrexed