Neoadjuvant PD-1 Antibody Plus Apatinib or Chemotherapy for Non-small Cell Lung Cancer

NCT04379739 | Active Not Recruiting Phase 2

• 1 other identifier: MA-NSCLC-II-001 (LungMate-003)
• Study Type: interventional
• Target: 89
• Locations: 1 country
• Sites: 1

Brief Summary

Immunotherapy with anti-programmed death 1 (PD-1) antibodies has revolutionized the treatment of metastatic and advanced NSCLC, but its application in neoadjuvant setting has not been well established. Results from a pilot clinical study reported the safety and feasibility of neoadjuvant PD-1 blockade. There are several neoadjuvant immunotherapy (NEOSTAR, LCMC3, NADIM, IMpower131) ongoing, and the preliminary results are reported in 2019 American Society of Clinical Oncology, which show promising therapeutic prospect. However, the therapeutic response rate (major pathologic response \[MPR\]) are not so good (20% - 45%) for PD-1 inhibitor monotherapy. To improve the therapeutic response, the investigators design a multiple-canter, open-label, phase II trial for stage II-III potentially resectable (resectable and initially unresectale) NSCLC. The participants will receive neoadjuvant PD-1 inhibitor (camrelizumab) combined with antiangiogenic drug (apatinib) or platinum-based chemotherapy.

Conditions

Non Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Major pathologic response (MPR)

  MPR is defined as the proportion of participants who have achieved major pathologic response (on routine hematoxylin and eosin staining, tumors with no more than 10% viable tumor cells) in all participants who have completed the neoadjuvant therapy before surgery.

  up to 5 months

Secondary Outcomes (5)

• 2-year OS

  up to 27 months

• Objective response rate (ORR)

  up to 4 months

• Disease-free survival (DFS)

  up to 60 months

• Overall survival (OS)

  up to 63 months

• Safety: frequency of severe adverse events

  up to 6 months

Study Arms (2)

camrelizumab + apatinib

EXPERIMENTAL

Neoadjuvant treatment stage: camrelizumab 200mg, q3w, i.v., 2-4 cycles; apatinib 250 mg, qd, p.o. 3 weeks per cycle, 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery 3-4 weeks after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.

Drug: Camrelizumab

camrelizumab + platinum-based chemotherapy

EXPERIMENTAL

Neoadjuvant treatment stage: camrelizumab 200mg, q3w, i.v., 2-4 cycles; platinum-based chemotherapy (squamous: carboplatin AUC5, gemcitabine 1000mg/m2; non-squamous: carboplatin AUC5, pemetrexed 500mg/m2) q3w, i.v., 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery 3-4 weeks after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.

Drug: Camrelizumab

Interventions

Camrelizumab DRUG

camrelizumab 200mg, q3w, i.v., 2-4 cycles;

Also known as: Apatinib, Platinum-based chemotherapy

camrelizumab + apatinib; camrelizumab + platinum-based chemotherapy

Eligibility Criteria

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

You may qualify if:

• Group A:
• Aged 18-75 years;
• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1;
• Histological or cytological diagnosis of NSCLC by needle biopsy, and clinical stage II-III according to the TNM classification (8th edition) validated by radiological examination or EBUS;
• At least 1 measurable lesion according to RECIST 1.1;
• Life expectancy is at least 12 weeks;
• Adequate hematological function, liver function and renal function:
• Hemoglobin ≤ 90 g/L (which can be maintained or exceeded by blood transfusion);
• Absolute neutrophil count (ANC) ≤ 1.5 \*10\^9/L;
• Platelet count ≤ 100 \* 10\^9/L;
• Total bilirubin ≤ 1.5 times of upper limit of normal (ULN);
• Alanine glutamate transaminase (ALT), straw glutamate transaminase (AST) and alkaline phosphatase (ALP) ≤ 2.5 \* ULN;
• Creatinine ≤ 1.5 \* ULN, Creatinine clearance rate ≤ 60ml/min;
• The international standardized ratio of prothrombin time (INR) ≤ 1.5 R in patients who have not received anticoagulation therapy, and the partial thrombin time (APTT) ≤ 1.5 \* ULN.
• Without systemic metastasis (including M1a, M1b and M1c);

You may not qualify if:

• Group A:
• The patient has undergone any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment, immunotherapy or Chinese medicine treatment, etc. (excluding the malignant tumors that were resected radically and did not recurrent more than 5 years);
• Non-squamous cell carcinoma with EGFR active mutation positive or ALK rearrangement;
• The patient suffered from other cancers (except cervical carcinoma in situ, cured basal cell carcinoma and bladder epithelial tumor \[including Ta and Tis\]) within 5 years before the enrollment;
• The patient suffers from any active autoimmune disease or have the history of autoimmune disease, such as uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (can be included after hormone replacement therapy), tuberculosis; Note: The patients with complete remission of childhood asthma and without any interventions in adult life could be included. The patients with skin diseases (like vitiligo, psoriasis or alopecia) who do not need systematic therapy could be included.
• Suffering or having the history of pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, radiological pneumonia, drug-induced pneumonia, radiologically confirmed active pneumonia, or severe impairment of lung function;
• Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids \>10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy with a dose of less than 10 mg/ day of prednisone are permitted;
• Allergy to the test drug;
• The patient is a carrier of active hepatitis B, hepatitis C or HIV;
• Pregnancy or breast-feeding women; child-bearing participants who could not or are unwilling to take contraceptive measures.
• Patients with eurological or psychiatric disorders history were lack of treatment compliance;
• Other situations in which investigators thought the patients not suit to be included.
• Group B:
• The patient has undergone any systemic anti-cancer treatment for NSCLC, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment, immunotherapy or Chinese medicine treatment, etc. (excluding the malignant tumors that were resected radically and did not recurrent more than 5 years);
• Non-squamous cell carcinoma with EGFR active mutation positive or ALK rearrangement;

Sponsors & Collaborators

• Shanghai Pulmonary Hospital, Shanghai, China: lead

Study Sites (1)

Shanghai Pulmonary Hospital

Shang'ai, Shanghai Municipality, 200433, China

Location

Related Publications (1)

• Ji S, Sheng Z, Bian D, Bao M, Jin K, Zhang W, Zhu X, Sun F, Xia H, Zhang H, Shen Z, Yu H, Zhang L, Huang J, Peng Z, Song N, Wang H, Qian B, Zhu Y. Neoadjuvant camrelizumab plus chemotherapy or apatinib for resectable stage IIA-IIIA NSCLC: a multicenter, two-arm, phase II exploratory trial. BMC Med. 2025 Jul 18;23(1):429. doi: 10.1186/s12916-025-04250-4.

  PMID: 40682106 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

camrelizumab; apatinib; Platinum Compounds

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Inorganic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of thoracic department

Study Record Dates

• First Submitted: April 19, 2020
• First Posted: May 7, 2020
• Study Start: July 26, 2020
• Primary Completion: June 29, 2022
• Study Completion (Estimated): December 30, 2026
• Last Updated: December 6, 2023

Record last verified: 2023-11

Locations

CN (1)