Immunotherapy With Non-Ablative Radiation in Previously Untreated Patients With Stage IV NSCLC

NCT05691829 | Terminated Phase 2 Results DMC FDA Drug

• 1 other identifier: 22-00673
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to test if low dose radiation, which is routinely used in treating patients with lung cancer for symptom control, can improve the results from the standard treatment with pembrolizumab and chemotherapy. In this study, only individuals who have NSCLC that is advanced (Stage IV), or has come back (recurred), will be able to participate.

Conditions

NSCLC Stage IV

Keywords

Lung; Immunotherapy; Fraction non-ablative radiation; untreated patients; metastatic

Outcome Measures

Primary Outcomes (1)

• Percent of Participants With a Best Overall Response of Complete Response (CR) or Partial Response (PR) by End of Treatment Cycle 4

  Defined as the best response recorded from the start of the study treatment until the end of treatment Cycle 4, either Complete Response or Partial Response. A CR is defined as the disappearance of all target lesions (TLs) and reduction in the short axis measurement of all pathologic lymph nodes to ≤10 mm. A PR is defined as at least a 30% decrease in the sum of the longest diameter (SLD) of TLs, taking as reference the baseline SLD.

  Up to Week 12 (End of Cycle 4 - each cycle is 21 days)

Secondary Outcomes (3)

• Progression-Free Survival (PFS) at Final Follow-Up

  From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks

• Overall Survival (OS) at Final Follow-Up

  From enrollment until the first documented and confirmed progression of disease, death, date last follow-up, or end of study; assessed up to 81 weeks

• Percentage of Participants With an Objective Response

  Week 52

Study Arms (1)

Untreated Patients With Stage IV NSCLC

EXPERIMENTAL

Participants will receive radiation in concert with starting chemotherapy with pembrolizumab for up to 6 cycles (18 weeks), followed by continued treatment with pembrolizumab (standard of care). Patients will be followed for 1 year following the completion of the core study period of 6 cycles.

Drug: Pembrolizumab; Radiation: Radiation; Drug: Chemotherapy

Interventions

Pembrolizumab DRUG

Pembrolizumab 200mg solution administered intravenously every 3 weeks for 6 cycles followed by maintenance therapy until progression of disease or unacceptable toxicity (standard of care). Administered alongside chemotherapy.

Also known as: MK-3475

Untreated Patients With Stage IV NSCLC

Radiation RADIATION

One-time, up-front radiation delivered at up to five metastatic subsites at a 4 Gy x 5 radiation dose fractionation schedule. Radiation will be delivered within five days before or after initiation of first cycle of pembrolizumab treatment. Radiation modality and technique will be determined at the discretion of the treating radiation oncologist.

Untreated Patients With Stage IV NSCLC

Chemotherapy DRUG

Administered alongside pembrolizumab every 3 weeks for 6 cycles per institutional standard of care. For non-squamous, the standard chemotherapy option of choice is carboplatin and pemetrexed. For squamous cell carcinoma, the chemotherapy used would be carboplatin and paclitaxel or nab-paclitaxel

Untreated Patients With Stage IV NSCLC

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Histologically documented, metastatic NSCLC with no previous systemic therapy
• At least 2 distinct measurable metastatic sites, which are 1 cm or larger; patients can have radiation to multiple measurable disease sites as clinically indicated, however, there must be at least 1 measurable non-radiated target lesion for response assessment.
• Agreeable to provide archival tissue for correlative studies; if no archival tissue available may obtain an exemption by the study team.
• Be at least 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1.
• Have a performance status of ≤1 ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 2, all screening labs should be performed within 10 days of treatment initiation
• Have one measurable lesion of at least 1 cm outside the planned radiation field (defined as not receiving direct beam from any of the treatment portals).
• Female subject of childbearing potential should have a negative urine or serum pregnancy 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.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section - Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
• Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section- Contraception, starting with the first dose of study therapy through 120 days after the last dose of study therapy. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.

You may not qualify if:

• Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Has a known history of active TB (Bacillus Tuberculosis)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Has had prior chemotherapy, immunotherapy or targeted small molecule therapy within 6 months prior to study Day 1.
• Patient who have previously received radiation overlapping, as determined by the treating radiation oncologist, with the current planned radiation treatment fields are ineligible.
• Patient's treated with whole brain radiation therapy are ineligible.
• Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases (with SRS and/or neurosurgery) may participate provided they are clinically stable and, have no evidence of new or enlarging brain metastases and also are off steroids 3 days prior to dosing with study medication.
• Patients who have not recovered (i.e., ≤ Grade 2 or at baseline) from adverse events due to a previously administered agent. \*Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy. Has active autoimmune disease that has required systemic treatment in the 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.
• Has history of autoimmune disorders, (non-infectious) pneumonitis that required steroids, evidence of interstitial lung disease or active, non-infectious pneumonitis.
• Has an active infection requiring systemic therapy.
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
• Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Neoplasm Metastasis

Interventions

pembrolizumab; Radiation; Drug Therapy

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Physical Phenomena; Therapeutics

Results Point of Contact

• Title: Fraustina Hsu
• Organization: NYU Langone Health

Fraustina.Hsu@nyulangone.org

646-754-7124

Study Officials

• Vamsidhar Velcheti

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 11, 2023
• First Posted: January 20, 2023
• Study Start: January 24, 2023
• Primary Completion: June 20, 2024
• Study Completion: April 21, 2025
• Last Updated: July 29, 2025
• Results First Posted: July 29, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Vamsidhar.Velcheti@nyulangone.org. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)