The Effect of Toripalimab Plus Radiotherapy in Patients With Operable Stage II-IIIA (N+) Non Small Cell Lung Cancer

NCT05798845 | Recruiting Phase 2 DMC

• 1 other identifier: neoRT-Lung
• Study Type: interventional
• Target: 124
• Locations: 1 country
• Sites: 1

Brief Summary

This randomized phase II trial is to explore the clinical efficacy, safety and feasibility of neoadjuvant immunotherapy plus radiotherapy compared with neoadjuvant immunotherapy plus chemotherapy in operable stage II-IIIA (N+) non small cell lung cancer (NSCLC) and the optimal radiotherapy pattern.

Conditions

NSCLC

Keywords

neoadjuvant immunotherapy; radiotherapy

Outcome Measures

Primary Outcomes (1)

• Pathlogical complete remission (pCR) rate

  Pathlogical complete remission rate

  1 year

Secondary Outcomes (11)

• major pathologic response (MPR) of primary tumor

  1 year

• Perioperative complications

  1 year

• Completion of surgery

  intraoperative

• Rate of R0 resection

  1 year

• treatment emergent adverse event (TEAE)

  1 year

Study Arms (2)

Arm A

EXPERIMENTAL

Radiation: primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 3Gy/3Fx, d1-3, d22-24 (2 cycles) ; Drug: toripalimab 240mg ivgtt d4, d24 (2 cycles)

Radiation: SBRT+LDRT; Drug: Toripalimab

Arm B

ACTIVE COMPARATOR

Drug: Chemotherapy + toripalimab 240mg ivgtt d1, d22 (2 cycles) Chemotherapy regimen: Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum. Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Drug: Chemotherapy drug; Drug: Toripalimab

Interventions

Chemotherapy drug DRUG

Non-squamous carcinoma: pemetrexed + platinum or paclitaxel + platinum Squamous carcinoma: paclitaxel + platinum or gemcitabine + platinum

Arm B

Toripalimab DRUG

toripalimab 240mg ivgtt d4, d24 (2 cycles)

Arm A

SBRT+LDRT RADIATION

primary tumor SBRT, DT: 24Gy/3Fx, d1-3; positive lymph nodes LDRT, DT: 3Gy/3Fx, d1-3, d22-24 (2 cycles)

Arm A

Eligibility Criteria

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

You may qualify if:

• Age 18 to 75 years old, gender is not limited.
• ECOG performance status 0-1.
• non-small cell lung cancer diagnosed by pathology.
• sufficient tumor tissue available for biomarker analysis.
• clinical staging of cT1-2N1-2M0 or T3N1M0, stage II-IIIA (8th UICC staging criteria).
• Patients with distant metastases ruled out by CT or PET/CT and physically assessed as acceptable for radical lung cancer surgery.
• histomolecular pathology confirming the absence of classic driver oncogene mutations in EGFR, ALK, or ROS1.
• Basic normal function of all organs (laboratory test results within 1 week prior to enrollment).
• Bone marrow function: absolute neutrophil count (ANC) ≥ 1.5x109 /L, platelet count ≥ 100x109 /L, hemoglobin ≥ 9g/dL.
• Liver: serum total bilirubin ≤ 1.5 times the upper limit of normal; ALT and AST ≤ 2.5 times the upper limit of normal.
• Kidney: blood creatinine level ≤ 1.5 times the upper limit of normal or creatinine clearance ≥ 60 ml/min and urea nitrogen ≤ 200 mg/L.
• Urine protein \<+, if urine protein + then total 24 hour protein must be \<500mg.
• Blood glucose: within normal range and/or with diabetic patients on treatment but with stable blood glucose control.
• Pulmonary function: baseline FEV1 of at least 2L; if baseline FEV1 \< 2L then FEV1 \> 800ml is expected after surgery as assessed by a surgical specialist.
• Cardiac function: no myocardial infarction within 1 year; no unstable angina; no symptomatic severe arrhythmia; no cardiac insufficiency.

You may not qualify if:

• Pathology suggestive of compound small cell lung cancer, etc.
• History of previous lobectomy, radiotherapy or chemotherapy.
• Those with concurrent second primary carcinoma and a history of previous malignancy of less than 5 years (except for completely cured cervical carcinoma in situ or basal cell or squamous epithelial cell skin cancer).
• Patients with any active autoimmune disease or a history of autoimmune disease (e.g., interstitial pneumonia, uveitis, enterocolitis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism, etc.).
• Have an active infection requiring systemic treatment or a history of active tuberculosis.
• Known history of human immunodeficiency virus (HIV) or active chronic Hepatitis C or Hepatitis B virus infection or any uncontrolled active systemic infection requiring intravenous (iv) antimicrobial treatment.
• Those with known presence or coexistence of other uncontrollable diseases that are not amenable to surgical treatment
• Physical examination or clinical trial finds that, in the opinion of the investigator, may interfere with the results or place the patient at increased risk for treatment complications
• Prior interstitial lung disease, drug-induced interstitial disease or any clinically evident active interstitial lung disease with idiopathic pulmonary fibrosis on baseline CT scan; uncontrolled massive pleural or pericardial effusion
• Unstable systemic concomitant disease (active infection, moderate to severe chronic obstructive pulmonary disease, poorly controlled hypertensive disease, unstable angina pectoris, congestive heart failure, myocardial infarction occurring within 6 months, severe mental disorder requiring medication for control, liver, renal or other metabolic disease, neuropsychiatric pathology such as Alzheimer's disease)
• History of congenital or acquired immunodeficiency disorders or organ transplantation
• Received any of the following treatments:
• Prior radiotherapy, treatment with anti PD-1, anti PD-L1 or anti PD-L2 drugs, or other drugs that synergistically inhibit T-cell receptors such as CTLA-4, OX-40, CD137.
• Having received any investigational drug within 4 weeks
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or an interventional clinical study follow-up

Sponsors & Collaborators

• Shanghai Chest Hospital: lead
• Shanghai Junshi Bioscience Co., Ltd.: collaborator

Study Sites (1)

Shanghai Chest Hospital

Shanghai, Shanghai Municipality, 200030, China

RECRUITING

Related Publications (9)

• Howlader N, Forjaz G, Mooradian MJ, Meza R, Kong CY, Cronin KA, Mariotto AB, Lowy DR, Feuer EJ. The Effect of Advances in Lung-Cancer Treatment on Population Mortality. N Engl J Med. 2020 Aug 13;383(7):640-649. doi: 10.1056/NEJMoa1916623.

  PMID: 32786189 BACKGROUND

• Rami-Porta R, Bolejack V, Crowley J, Ball D, Kim J, Lyons G, Rice T, Suzuki K, Thomas CF Jr, Travis WD, Wu YL; IASLC Staging and Prognostic Factors Committee, Advisory Boards and Participating Institutions. The IASLC Lung Cancer Staging Project: Proposals for the Revisions of the T Descriptors in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer. J Thorac Oncol. 2015 Jul;10(7):990-1003. doi: 10.1097/JTO.0000000000000559.

  PMID: 26134221 BACKGROUND

• Ko EC, Raben D, Formenti SC. The Integration of Radiotherapy with Immunotherapy for the Treatment of Non-Small Cell Lung Cancer. Clin Cancer Res. 2018 Dec 1;24(23):5792-5806. doi: 10.1158/1078-0432.CCR-17-3620. Epub 2018 Jun 26.

  PMID: 29945993 BACKGROUND

• Wang Y, Liu ZG, Yuan H, Deng W, Li J, Huang Y, Kim BYS, Story MD, Jiang W. The Reciprocity between Radiotherapy and Cancer Immunotherapy. Clin Cancer Res. 2019 Mar 15;25(6):1709-1717. doi: 10.1158/1078-0432.CCR-18-2581. Epub 2018 Nov 9.

  PMID: 30413527 BACKGROUND

• Demaria S, Coleman CN, Formenti SC. Radiotherapy: Changing the Game in Immunotherapy. Trends Cancer. 2016 Jun;2(6):286-294. doi: 10.1016/j.trecan.2016.05.002.

  PMID: 27774519 BACKGROUND

• Bernstein MB, Krishnan S, Hodge JW, Chang JY. Immunotherapy and stereotactic ablative radiotherapy (ISABR): a curative approach? Nat Rev Clin Oncol. 2016 Aug;13(8):516-24. doi: 10.1038/nrclinonc.2016.30. Epub 2016 Mar 8.

  PMID: 26951040 BACKGROUND

• Theelen WSME, Chen D, Verma V, Hobbs BP, Peulen HMU, Aerts JGJV, Bahce I, Niemeijer ALN, Chang JY, de Groot PM, Nguyen QN, Comeaux NI, Simon GR, Skoulidis F, Lin SH, He K, Patel R, Heymach J, Baas P, Welsh JW. Pembrolizumab with or without radiotherapy for metastatic non-small-cell lung cancer: a pooled analysis of two randomised trials. Lancet Respir Med. 2021 May;9(5):467-475. doi: 10.1016/S2213-2600(20)30391-X. Epub 2020 Oct 20.

  PMID: 33096027 BACKGROUND

• Vanpouille-Box C, Alard A, Aryankalayil MJ, Sarfraz Y, Diamond JM, Schneider RJ, Inghirami G, Coleman CN, Formenti SC, Demaria S. DNA exonuclease Trex1 regulates radiotherapy-induced tumour immunogenicity. Nat Commun. 2017 Jun 9;8:15618. doi: 10.1038/ncomms15618.

  PMID: 28598415 BACKGROUND

• Altorki NK, McGraw TE, Borczuk AC, Saxena A, Port JL, Stiles BM, Lee BE, Sanfilippo NJ, Scheff RJ, Pua BB, Gruden JF, Christos PJ, Spinelli C, Gakuria J, Uppal M, Binder B, Elemento O, Ballman KV, Formenti SC. Neoadjuvant durvalumab with or without stereotactic body radiotherapy in patients with early-stage non-small-cell lung cancer: a single-centre, randomised phase 2 trial. Lancet Oncol. 2021 Jun;22(6):824-835. doi: 10.1016/S1470-2045(21)00149-2. Epub 2021 May 18.

  PMID: 34015311 BACKGROUND

MeSH Terms

Interventions

toripalimab

Central Study Contacts

Xiaolong Fu, MD

CONTACT

862122200000; xlfu1964@126.com

Wen Feng, MD

CONTACT

862122200000; fengwen412@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: director,department of radiation oncology

Study Record Dates

• First Submitted: January 18, 2023
• First Posted: April 5, 2023
• Study Start: February 20, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: March 11, 2026

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)