The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial

NCT03523702 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 2018-8945
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this study is to explore if, for locally advanced non-small cell lung cancer patients whose tumors have high levels of PD-L1 (a marker associated with benefits from immunotherapy), a combination of immunotherapy and a personalized 4-week radiotherapy course could be more effective than standard treatment, which is a combination of chemotherapy and radiotherapy.

Conditions

Non-small Cell Lung Cancer, NSCLC

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival (PFS)

  To characterize progression-free survival (PFS) rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%, the percentage of participants with PFS at 12 months will be reported.

  12 months

Secondary Outcomes (5)

• Freedom From Distant Metastasis

  Up to 18 months following completion of treatment, up to 30 months total

• Intrathoracic Disease Progression

  Up to 18 months following completion of treatment, up to 30 months total

• Overall Survival (OS)

  1 year and 2 years following completion of treatment, up to 3 years total

• Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST)

  2 months

• Unplanned Hospitalization Rate

  Up to 18 months following completion of treatment, up to 30 months total

Study Arms (1)

PembroRT

EXPERIMENTAL

Subjects with PD-L1 expression ≥ 50%: Combination of sequential pembrolizumab (200mg every 3 weeks) and accelerated, dose-painted radiotherapy for locally advanced NSCLC patients with high (≥ 50%) PD-L1 expression. Subjects with PD-L1 expression \< 50%: Patients with PD-L1 expression \< 50% will also be enrolled and treated with standard concurrent chemoradiotherapy

Drug: PembroRT

Interventions

PembroRT DRUG

Patients whose tumors are found to have high (≥ 50%) PD-L1 expression will automatically be placed in the PembroRT group. These patients will receive three intravenous treatments with pembrolizumab, followed by four weeks of daily radiotherapy, followed by up to 12 more treatments with pembrolizumab. Pembrolizumab is given as an intravenous infusion once every three weeks. This treatment course will last, in total, up to one year. Patients whose tumors are found to have low (\< 50%) PD-L1 will be treated with a standard-o-care regimen and not be a part of this clinical trial.

PembroRT

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all the following criteria apply:
• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of non-small cell lung cancer will be enrolled in this study.
• Previously untreated, pathologically proven NSCLC with measurable disease (at least 1 unidimensional, radiographically measurable lesion based on RECIST v1.1) and one of the following stages: (prior resection for early stage disease is allowed)
• AJCC version 8 Stage II disease, medically or technically unresectable
• AJCC version 8 Stage III disease
• Whole body PET/CT within 42 days prior to study entry demonstrating hypermetabolic pulmonary lesion(s) and/or thoracic lymph node(s). If PET/CT was obtained more than 42 days prior to study entry and is not repeated, CT within 28 days prior to study entry demonstrating no evidence of metastatic disease is required.
• MRI of the brain or head CT with contrast within 42 days prior to study entry.
• PFTs within 42 days of study entry
• ECOG performance status 0-1
• Adequate end-organ function, based on routine clinical and laboratory workup:
• ANC \>1,500 cells/µl, Platelets ≥ 100,000 cells/µl, Hemoglobin ≥ 9.0 g/dl
• Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min
• Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN
• International normalized ratio (INR) (or prothrombin time (PT)) and activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy, as long as values are within the intended therapeutic range
• Thyroid stimulating hormone (TSH) within normal limits. If TSH is not within normal limits, the participant may be eligible if T3 and free T4 are within normal limits.

You may not qualify if:

• Not a woman of childbearing potential (WOCBP) as defined in the Appendix
• A WOCBP who agrees to follow the contraceptive guidance in the Appendix during the treatment period and for at least 120 days after the last dose of study treatment with pembrolizumab (pembroRT cohort) or at least 180 days after the last dose of chemotherapy (chemoRT cohort).
• A male participant must agree to use contraception during the treatment period and for at least 28 days after the last dose of study treatment and refrain from donating sperm during this period.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Participants are excluded from the study if any of the following criteria apply:
• Malignant pleural or pericardial effusion, based on clinical, imaging, or pathologic evaluation.
• Systemic therapy for lung cancer within the past year.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Contraindication to protocol-specified radiotherapy, such as prior thoracic radiotherapy or active serious collagen vascular disease (e.g. scleroderma).
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Active malignancy other than lung cancer that requires active treatment other than hormonal therapy or is deemed by the treating physicians to be likely to affect the subject's survival duration.
• A history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
• Active infection requiring antimicrobial therapy.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for

Sponsors & Collaborators

• Montefiore Medical Center: lead
• Henry Ford Cancer Institute: collaborator
• Merck Sharp & Dohme LLC: collaborator
• University of Michigan: collaborator
• New York University: collaborator

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

Related Publications (2)

• https://www.redjournal.org/article/S0360-3016(24)00859-9/fulltext

  RESULT

• Ohri N, Jolly S, Cooper BT, Kabarriti R, Bodner WR, Klein J, Guha C, Viswanathan S, Shum E, Sabari JK, Cheng H, Gucalp RA, Castellucci E, Qin A, Gadgeel SM, Halmos B. Selective Personalized RadioImmunotherapy for Locally Advanced Non-Small-Cell Lung Cancer Trial (SPRINT). J Clin Oncol. 2024 Feb 10;42(5):562-570. doi: 10.1200/JCO.23.00627. Epub 2023 Nov 21.

  PMID: 37988638 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Nitin Ohri
• Organization: Albert Einstein College of Medicine

nitin.ohri@einsteinmed.edu

718-920-7750

Study Officials

• Nitin Ohri, MD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

• Nitin Ohri, MD

  Montefiore Medical Center

  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

Model Details: Single arm study with 2 cohort (PembrolizumabRT cohort) part of the trial and SOC cohort (not part of the trial)

Study Record Dates

• First Submitted: May 2, 2018
• First Posted: May 14, 2018
• Study Start: August 30, 2018
• Primary Completion: November 18, 2022
• Study Completion: November 18, 2022
• Last Updated: April 9, 2026
• Results First Posted: December 3, 2024

Record last verified: 2026-04

Locations

US (1)