Surgery After Verifying Existing Disease in Locally Advanced Operable Lung Cancer: A Pilot Study

NCT06743555 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: 2025-12255
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The SAVED LUNG study is a pilot Phase I trial evaluating safety and feasibility of observation versus standard-of-care surgery in operable Stage II-III (excluding N3) NSCLC patients (PD-L1 ≥50%) who achieve complete clinical response following neoadjuvant platinum-doublet chemotherapy and immunotherapy. Participants are randomized to observation or surgery after rigorous restaging, with primary endpoints focusing on safety and feasibility. Secondary objectives include rates of cross-over to surgery, event-free survival, and overall survival, while exploratory endpoints examine ctDNA clearance and its association with clinical response.

Conditions

Non-Small Cell Lung Cancer; Immunotherapy; Neoadjuvant Therapy; Thoracic Surgery; Complete Response

Keywords

NSCLC; Neoadjuvant immunotherapy; Complete response; Surveillance; PD-L1

Outcome Measures

Primary Outcomes (2)

• Safety

  Adverse events will be determined as type and grade using the CTCAE v5.0.

  From randomization through 5 years of follow-up

• Feasibility

  Recruitment rate will be defined as the total number of patients recruited (consented) out of the total number of patients approached.

  First two years of the study

Secondary Outcomes (5)

• Complete clinical response

  Restaging 3 weeks after completion of neoadjuvant therapy (3 cycles of nivolumab and platinum-doublet chemotherapy)

• Cross-over to surgery

  From randomization through 5 years of follow-up

• Event-free survival (EFS) at 12 months

  12 months following randomization

• Overall survival (OS) at 12 months

  12 months following randomization

• Circulation tumor DNA (ctDNA) clearance

  3 weeks post-randomization (surveillance arm) or 3 weeks post-surgery (standard-of-care surgery arm)

Study Arms (2)

Standard-of-care surgery

ACTIVE COMPARATOR

Participants undergo surgery followed by the same surveillance schedule as Arm A. ctDNA testing is conducted 3 weeks post-surgery and again at 6 months. Surveillance includes low-dose CT scans, physical examinations, and ECOG assessments every 3 months for 12 months, with long-term monitoring at regular intervals up to 5 years.

Procedure: Standard-of-care surgery

Observation without surgery

EXPERIMENTAL

Participants undergo surveillance without surgery, including a low-dose CT scan of the thorax and upper abdomen, ECOG assessment, and physical examination every 3 months for the first 12 months. Additional ctDNA testing is performed 3 weeks post-randomization and at 6 months. Long-term follow-up includes similar assessments every 6-12 months up to 5 years.

Other: Observation without surgery

Interventions

Observation without surgery OTHER

Patients randomized to this arm will forego standard-of-care thoracic surgery and will undergo strict surveillance based on serial radiological follow-up and ctDNA monitoring

Observation without surgery

Standard-of-care surgery PROCEDURE

Patients randomized to this arm will undergo standard-of-care thoracic surgery and undergo post-operative surveillance with serial radiological follow-up and ctDNA monitoring

Standard-of-care surgery

Eligibility Criteria

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

You may qualify if:

• \> 18 years of age
• The participant has provided documented informed consent for the trial.
• Histologically confirmed (by core biopsy) NSCLC and confirmed clinical stages II-III (excluding N2) NSCLC (AJCC 8th edition) amenable to receive neoadjuvant chemo-immunotherapy defined by: nivolumab 3mg/kg Q3W in combination with platinum doublet chemotherapy (cisplatin or carboplatin with paclitaxel or pemetrexed Q3W) for 3 cycles.
• PD-L1 tumor proportion score \>50%
• Has no history of immunodeficiency, HBV, HCV, HIV.
• For female participants:
• Has no active pregnancy (Refer to "Female participants").
• For a woman of child-bearing potential (WOCBP), use of a contraceptive method that is highly effective (with a failure rate of \<1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least 180 days after the last dose of study intervention and agrees not to donate eggs (ova, oocytes) to others or freeze/store for her own use for the purpose of reproduction during this period.
• A WOCBP must have a negative highly sensitive pregnancy test (\[urine or serum\] as required by local regulations) within either 24 hours (urine) or 72 hours (serum) before the first dose of study intervention.
• If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive.
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
• Has adequate hematological, renal and hepatic function per Investigator discretion required for platinum-doublet chemotherapy plus immunotherapy.
• Has signed the written consent.

You may not qualify if:

• Has one of the following tumor locations/types:
• NSCLC involving the superior sulcus
• Large cell neuro-endocrine cancer (LCNEC)
• Sarcomatoid tumor
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• Has had an allogenic tissue/solid organ transplant.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the participant's participation for the full duration of the trial, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperating with the requirements of the trial.
• Has a known additional malignancy that is progressing or requires active treatment within the past (5 years). Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, bladder carcinoma, or carcinoma in situ (eg, in situ cervical cancer or breast carcinoma) that have undergone potentially curative therapy are not excluded.

Sponsors & Collaborators

• Centre hospitalier de l'Université de Montréal (CHUM): lead

Study Sites (1)

Centre hospitalier de l'Université de Montréal (CHUM)

Montreal, Quebec, H2X 3E4, Canada

Location

Related Publications (1)

• Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.

  PMID: 29658848 RESULT

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Pathologic Complete Response

Interventions

Observation; Surgical Procedures, Operative

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Disease Progression; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Methods; Investigative Techniques

Study Officials

• Antoine Desilets, MD, MSc

  Centre hospitalier de l'Université de Montréal (CHUM)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Antoine Desilets, MD, MSc

CONTACT

514-890-8444; antoine.desilets.med@ssss.gouv.qc.ca

Wiam Belkaid, PhD

CONTACT

514-836-3273; wiam.belkaid.chum@ssss.gouv.qc.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2024
• First Posted: December 20, 2024
• Study Start: May 1, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2032
• Last Updated: April 28, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)