Neoadjuvant Platform Trial in Non-Small Cell Lung Cancer

Neoadjuvant Platform Trial in Patients With Surgically Resectable Non-Small Cell Lung Cancer (NSCLC)

This study is being done to answer the following question: What are the effects of new treatments on non-small cell lung cancer before surgery?

Study Overview

• Status: Active, not recruiting
• Conditions: NSCLC
• Intervention / Treatment: Drug: JDQ443

Detailed Description

The purpose of the pre-study screening is to test for biomarkers. The testing will be done using a sample of your tumor tissue. Each substudy will be looking at what effects a new drug has on the patients and their lung cancer, as well as any side effects of the treatment. The purpose of each substudy is to see if the biomarkers that were identified at screening can be used to determine treatment outcomes, like how the cancer cells respond to treatment and whether the study drug will shrink the tumour before surgery and prevent it from returning after surgery.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 0V9
      • CancerCare Manitoba
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Kingston Health Sciences Centre
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre Research Inc.
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network
  • Quebec
    • Montreal, Quebec, Canada, H2X 3E4
      • CHUM-Centre Hospitalier de l'Universite de Montreal
    • Montreal, Quebec, Canada, H4A 3J1
      • The Research Institute of the McGill University
    • Québec, Quebec, Canada, G1V 4G5
      • University Institute of Cardiology and

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Histologically confirmed diagnosis of primary NSCLC within 90 days of enrollment to a substudy, according to WHO Classification of Tumours
• Unless otherwise specified in a substudy, patients must be classified as Stage IA2 to IIIA according to the AJCC 8th edition TNM classification with disease that is amenable to anatomical surgical resection.
• Pre-surgical staging of patients with newly diagnosed lung cancer should include: CT thorax, abdomen and pelvis; PET scan imaging; Brain MRI or CT brain with IV contrast. Patients with mediastinal lymph nodes suspicious for metastases on PET imaging are required to undergo invasive staging by EBUS or mediastinoscopy to confirm or disprove pathological involvement of suspected nodes.
• All patients must have evaluable disease as defined by RECIST 1.1 although measurable disease is recommended.
• Patients that are eligible for one or more substudies must consent for release of tissue biopsies, surgical specimens and blood samples for conduct of tissue analyses. If there is insufficient tissue to conduct the proposed research studies without exhausting the diagnostic biopsies, please consult CCTG
• Patients must be ≥ 18 years of age
• No prior anticancer therapy for treatment of NSCLC. Patients with a history of NSCLC treated in the curative setting may be eligible but must be discussed with CCTG prior to enrollment
• Patient must have an ECOG performance status of 0 or 1

• Patients with synchronous primary tumours may be eligible if all of the following conditions are met:

  • The synchronous tumour is located within the planned resection area
  • The radiological appearance of the tumour is compatible with ground-glass opacity (GGO)
  • The synchronous tumour is not FDG-avid on PET imaging
  • The local multidisciplinary thoracic oncology tumour board has approved the surgical treatment plan
• Surgery for participants enrolled on this protocol will be according to generally accepted standards of care. Operative approach (VATS, RATS vs open) will be determined by the surgeon. Accepted types of resection must aim to achieve an R0 resection, as defined by the IASLC, including the highest resected mediastinal being negative for carcinoma.
• Unless otherwise specified in specific substudies, surgery must be performed between 2 to 4 weeks following the last dose of neoadjuvant therapy
• Patients must have adequate organ and marrow function within 7 days prior to enrollment. Some substudies may require different cutoff values.
• Patient consent must be appropriately obtained in accordance with applicable local and regulatory requirements.
• Patient is able and willing to complete the Patient Related Outcomes questionnaire
• Patients must be accessible for treatment and follow-up.
• Protocol treatment is to begin within 2 working days of patient enrollment
• Women/men of childbearing potential must have agreed to use a highly effective contraceptive method

Exclusion Criteria:

• Presence of locally advanced, unresectable cancer (regardless of stage), or metastatic cancer (Stage IV).
• Patients with a history of other malignancy may be eligible if curatively treated and/or the malignancy does not affect the determination of safety or efficacy of the investigational regimen (must be confirmed with CCTG).

• Clinically significant, uncontrolled cardiac disease and/or recent cardiac events (within 6 months), such as:

  • Unstable angina or myocardial infarction within 6 months prior to enrollment;
  • Symptomatic congestive heart failure (defined as New York Heart Association Grade II or greater);,
  • Documented cardiomyopathy;,
  • Clinically significant cardiac arrhythmias; (Note: patients with clinically controlled, asymptomatic atrial arrhythmias without any ventricular function compromise may be eligible; please consult CCTG).
  • Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mm Hg and/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, unless controlled prior to first dose of study treatment.
  • Patients with a significant cardiac history, even if controlled, should have LVEF ≥ 50%

• History or current diagnosis of ECG abnormalities indicating significant risk of safety for participants participating in the study such as:

  • Concomitant clinically significant cardiac arrhythmias e.g. sustained ventricular tachycardia, and clinically significant second or third-degree AV block without a pacemaker;
  • History of familial long QT syndrome or known family history of Torsades de Pointes;
  • Resting QT interval corrected with Fridericia's formula (QTcF) > 480 msec on screening ECG or congenital long QT syndrome.
• Patients with prior allogenic bone marrow transplant, double umbilical cord blood transplantation (dUCBT) or solid organ transplant.

• Patients with active or uncontrolled infections or with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol. This includes but is not limited to:

  • Known clinical diagnosis of tuberculosis;
  • Pneumonitis or any history of pneumonitis requiring steroids (any dose);
  • Known primary immunodeficiency;
  • For Hepatitis B (HBV), Hepatitis C (HCV) and human immunodeficiency virus (HIV) infections, requirements will be substudy dependent.
• History of hypersensitivity to any drugs in any substudy, or to drugs of similar chemical class.
• Concurrent treatment with other investigational drugs or anti-cancer therapy.
• Pregnant or breastfeeding women.
• Patients who are unable to swallow oral medication and/or have impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of the specific substudy drug(s)
• Patients with a history of non-compliance to medical regimens.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Neoadjuvant therapy (JDQ443) followed by surgery. (ARM CLOSED); If *MPR/cPR* - standard of care adjuvant treatment may be followed by experimental adjuvant therapy (JDQ443) *Major Pathological Response (MPR)/ Complete Pathological Response (cPR)	Drug: JDQ443; Dose will be assigned at enrollment

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Identify promising neoadjuvant treatment regimens for NSCLC for later validation in randomized clinical trials, by evaluating major pathological response rates (MPR)	3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Number and severity of adverse events as per CTCAE version 5.0	3 years
Overall response rate using RECIST 1.1	3 years
Event-free survival at 2 years	3 years
Completeness of surgical resection using the Residual (R) Tumor Classification	3 years
Access to surgery (rate of open, video-assisted and robotic-assisted thoracic surgery)	3 years
Rate (and reasons) of surgical access conversion (from video-assisted or robotic-assisted thoracic surgery to open surgery)	3 years
Extent of surgery (rate of surgery types: wedge resection, segmentectomy, lobectomy, completion lobectomy, sleeve lobectomy, bilobectomy, pneumonectomy, major airway resection, and other)	3 years
Extent of perihilar/lobar fibrosis and mediastinal adhesions (as per the Lee et al. (JTO, 2021) grading scale)	3 years
Tumour downstaging: rate of patients with post-surgical downstaging when comparing cTNM and pTNM	3 years
Pathological complete response rate (pCR)	3 years

Collaborators and Investigators

• Sponsor: Canadian Cancer Trials Group
• Collaborators: Novartis
• Investigators: Study Chair: Jonathan Spicer, McGill University, Montreal, QC Canada; Study Chair: Normand Blais, CHUM-Centre Hospitalier de l'Universite de Montreal, QC Canada

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2023
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): March 31, 2028

Study Registration Dates

• First Submitted: January 4, 2023
• First Submitted That Met QC Criteria: February 2, 2023
• First Posted (Actual): February 6, 2023

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; JDQ443
• Other Study ID Numbers: I242

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No