HX008 Plus Chemotherapy VS Pembrolizumab Plus Chemotherapy As the First-line Treatment in Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer

NCT04750083 | Unknown Phase 2

• 1 other identifier: HX008-NSCLC-II/III-01
• Study Type: interventional
• Target: 700
• Locations: 1 country
• Sites: 10

Brief Summary

This a phase II-III study. In the single-armed phase II period, HX008, a monoclonal antibody targeting PD-1, will be combined with pemetrexed+platinum (Investigators choice of cisplatin or carboplatin) chemotherapy to treat participants with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) who have not previously received systemic therapy for advanced disease. When the preliminary efficacy and safety data are acquired, a single-blinded phase III study will ensue, in which the efficacy and safety of HX008+pemetrexed+platinum VS pembrolizumab+pemetrexed+platinum in participants of the same population will be compared head-to-head with 1:1 randomization. The primary endpoints are safety and ORR (overall response rate) evaluated by the investigator in phase II study, and PFS evaluated by IRC (independent review committee) in phase III study. The primary hypothesis in phase III study is that HX008+pemetrexed+platinum is non-inferior to pembrolizumab+pemetrexed+platinum in terms of PFS (Progression-Free Survival).

Conditions

Nonsquamous Non-small Cell Lung Cancer

Outcome Measures

Primary Outcomes (3)

• Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 in phase II study

  12 months

• Objective Response Rate (ORR) in phase II study

  Percentage of subjects achieving complete response (CR) and partial response (PR)

  12 months

• Progression-Free Survival (PFS) in phase III study

  The time from the first study drug treatment to disease progression (PD) or to death of the subject due to any reason.

  24 months

Secondary Outcomes (6)

• Objective Response Rate (ORR) in phase III study

  24 months

• Progression-Free Survival (PFS) in phase II study

  24 months

• Duration of Response (DOR) in phase II and III study

  24 months

• 12-month PFS rate in phase II and III study

  24 months

• Overall survival (OS) in phase II and III study

  36 months

Study Arms (3)

phase II

EXPERIMENTAL

Thirty-sixty participants will receive HX008 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W for another 31 cycles.

Drug: HX008; Drug: pemetrexed; Drug: cisplatin/carboplatin

phase III-experimental

EXPERIMENTAL

Three hundred and twenty participants will receive HX008 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W for another 31 cycles.

Drug: HX008; Drug: pemetrexed; Drug: cisplatin/carboplatin

phase III-control

EXPERIMENTAL

Three hundred and twenty participants will receive pembrolizumab 200 mg intravenously (IV) PLUS pemetrexed 500 mg/m\^2 IV PLUS cisplatin 75 mg/m\^2 IV OR carboplatin Area Under the Curve (AUC) 5 IV on Day 1 of every 3-week cycle (Q3W) for 4 cycles followed by pembrolizumab 200 mg IV PLUS pemetrexed 500 mg/m\^2 IV Q3W for another 31 cycles.

Drug: Pembrolizumab; Drug: pemetrexed; Drug: cisplatin/carboplatin

Interventions

HX008 DRUG

HX008 200 mg intravenously (IV) on Day 1 of every 3-week cycle (Q3W) for up to 35 cycles

phase II; phase III-experimental

Pembrolizumab DRUG

Pembrolizumab 200 mg intravenously (IV) on Day 1 of Q3W for up to 35 cycles

phase III-control

pemetrexed DRUG

pemetrexed 500 mg/m\^2 IV on Day 1 of Q3W for up to 35 cycles

phase II; phase III-control; phase III-experimental

cisplatin/carboplatin DRUG

cisplatin 75 mg/m\^2 IV OR carboplatin AUC 5 IV on Day 1 of Q3W for 4 cycles

phase II; phase III-control; phase III-experimental

Eligibility Criteria

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

You may qualify if:

• Understood and signed an informed consent form.
• Age ≥ 18 years old, male or female.
• Have a histologically or cytologically confirmed diagnosis of stage IV (M1a or M1b- AJCC 7th edition) nonsquamous NSCLC.
• Have not received prior systemic treatment for their advanced/metastatic NSCLC. Subjects who received adjuvant or neoadjuvant therapy are eligible if the adjuvant/neoadjuvant therapy was completed at least 12 months prior to the development of metastatic disease.
• Have confirmation that EGFR or ALK-directed therapy is not indicated.
• Have at least one measurable lesion according to RECIST1.1. Lesions situated in previously irradiated areas could be considered as target lesions if progression has been demonstrated in such lesions. If measurable lesions exist in other areas, lesions in previous irradiated areas should be considered as non-target lesions.
• Have provided tumor tissue from locations not radiated prior to biopsy for determination of PD-L1 status prior to randomization. Formalin fixed specimens the subject has been diagnosed with metastatic disease will be preferred. Biopsies obtained prior to receipt of adjuvant/neoadjuvant chemotherapy will be permitted if recent biopsy is not feasible.
• Life expectancy ≥ 3 months.
• Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Score.
• Have adequate organ function as indicated by the following laboratory values:
• Blood routine: serum albumin ≥2.5g/dL; absolute neutrophil count (ANC) ≥1.5×10\^9/L; while blood cell count (WBC) ≥3×10\^9/L; platelet count (PLT) ≥100×10\^9/L; hemoglobin (HGB) ≥90 g/L (without blood transfusion within 4 weeks prior to enrollment);
• Renal function: creatinine clearance (CrCl) ≥50 mL/min;
• Liver function: Patients without liver metastases require alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤2.5×ULN. Patients with liver metastases require: ALT and AST≤5×ULN. Serum total bilirubin ≤1.5xULN or direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5xULN;
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy; OR activated Partial Thromboplastin Time (aPTT) or Partial Thromboplastin Time (PTT) ≤1.5 X ULN unless the subject is receiving anticoagulant therapy.
• If female of childbearing potential, have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

You may not qualify if:

• The subject must be excluded from participating in the trial if the subject:
• Has predominantly squamous cell histology NSCLC. Mixed tumors will be categorized by the predominant cell type; if small cell elements are present, the subject is ineligible.
• Before the first dose of trial treatment:
• Has received prior systemic cytotoxic chemotherapy or other antineoplastic therapy (e.g., erlotinib, crizotinib, cetuximab) for metastatic disease
• Had major surgery within 3 weeks prior to the first dose of trial treatment
• Has participated in other clinical trial within 4 weeks prior to the first dose
• Received radiation therapy to the lung that is \> 30 Gy within 6 months prior to the first dose
• Completed palliative radiotherapy within 7 days prior to the first dose
• Has received a live-virus vaccination within 30 days prior to the first dose. Seasonal flu vaccines that do not contain live virus are permitted.
• Has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, peritoneal carcinomatosis.
• Suffered from other malignant tumors in the past 5 years, except those with low risk of metastasis and death (5-year survival rate \> 90%), for instance, skin basal cell carcinoma, squamous cell carcinoma, and carcinoma in situ from cervix or other regions that have been adequately treated.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication. Stable brain metastases by this definition should be established prior to the first dose of study medication. Subjects with known untreated, asymptomatic brain metastases (ie, no neurological symptoms, no requirements for corticosteroids, no or minimal surrounding edema, and no lesion \>1.5 cm) may participate but will require regular imaging of the brain as a site of disease.
• Has a known sensitivity to macromolecular agents or any component of cisplatin, carboplatin or pemetrexed.
• Has a history of organ or stem-cell transplantation.
• Has active autoimmune disease that has required systemic treatment in 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.

Sponsors & Collaborators

• Taizhou Hanzhong biomedical co. LTD: lead

Study Sites (10)

Anhui Provincial Hospital

Hefei, Anhui, 230001, China

RECRUITING

Beijing Chaoyang Hospital ,Capital Medical University

Beijing, Beijing Municipality, 100020, China

RECRUITING

Beijing Cancer Hospital

Beijing, Beijing Municipality, 100142, China

RECRUITING

Peking University Third Hospital

Beijing, Beijing Municipality, 100191, China

RECRUITING

Harbin Medical University Cancer Hospital

Harbin, Heilongjiang, 150081, China

RECRUITING

Hunan Province Cancer Hospital

Changsha, Hunan, 410000, China

RECRUITING

Xiangya Hospital Central South University

Changsha, Hunan, 410000, China

RECRUITING

Liaoning Cancer Hospital & Insititute

Shenyang, Liaoning, 110042, China

RECRUITING

Shanghai Pulmonary Hospital

Shanghai, Shanghai Municipality, 200433, China

RECRUITING

Affiliated Hangzhou Cancer Hospital

Hangzhou, Zhejiang, 310002, China

RECRUITING

MeSH Terms

Interventions

pembrolizumab; Pemetrexed; Cisplatin; Carboplatin

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; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Central Study Contacts

Caicun Zhou, MD

CONTACT

021-65115006; caicunzhoudr@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Phase II is open-labelled with one arm, and phase III is single-blinded for the participants with 2 arms.
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 11, 2021
• Study Start: September 25, 2020
• Primary Completion: September 25, 2022
• Study Completion: September 25, 2023
• Last Updated: February 11, 2021

Record last verified: 2021-02

Locations

CN (10)