The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (SPRINT)

Plain English Summary

The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial is a Phase 2 clinical trial sponsored by Montefiore Medical Center studying Non-small Cell Lung Cancer, NSCLC. This trial tests a new combination of immunotherapy (pembrolizumab) and radiation therapy for advanced non-small cell lung cancer. It is for patients with locally advanced non-small cell lung cancer that has not been previously treated and has high levels of a marker called PD-L1. Participation involves receiving immunotherapy and a personalized 4-week course of radiation therapy, followed by more immunotherapy. Standard treatment for this condition typically involves chemotherapy and radiation therapy. The trial aims to enroll 25 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults (18+) with a confirmed diagnosis of non-small cell lung cancer that is locally advanced and hasn't been treated before. Patients must have measurable disease and specific stage criteria (Stage II or III, or Stage II with prior resection). Individuals with high PD-L1 expression (50% or more) in their tumors are eligible. Patients must have good organ function and an ECOG performance status of 0 or 1. This trial is studying Non-small Cell Lung Cancer, NSCLC, so participants generally need a confirmed diagnosis.

What They're Measuring

Progression-Free Survival (PFS) measures how long patients live without their cancer getting worse, assessed at 12 months. The specific primary outcome measures are: Progression-Free Survival (PFS) (12 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to see if a personalized approach combining immunotherapy with radiation can be more effective than standard chemotherapy and radiation for certain advanced lung cancer patients. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Non-small Cell Lung Cancer, NSCLC, where improved treatment options are needed.

Investor Insight

This trial explores a novel combination therapy for a specific subset of lung cancer patients, potentially offering a more targeted treatment option and indicating a move towards personalized medicine Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific immunotherapy and radiation schedule and what to expect during treatment. Be prepared for regular clinic visits for infusions, radiation sessions, and follow-up scans. Discuss any potential side effects with your medical team promptly. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NA
• Model: SINGLE_GROUP
• Masking: NONE
• Enrollment: 25 participants

Interventions

• DRUG: PembroRT — 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

Primary Outcomes

• Progression-Free Survival (PFS) (12 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

1. 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.
2. 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)

   1. AJCC version 8 Stage II disease, medically or technically unresectable
   2. AJCC version 8 Stage III disease
3. 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.
4. MRI of the brain or head CT with contrast within 42 days prior to study entry.
5. PFTs within 42 days of study entry
6. ECOG performance status 0-1
7. Adequate end-organ function, based on routine clinical and laboratory workup:

   1. ANC \>1,500 cells/µl, Platelets ≥ 100,000 cells/µl, Hemoglobin ≥ 9.0 g/dl
   2. Serum creatinine ≤ 1.5 x ULN or calculated creatinine clearance ≥ 50 ml/min
   3. Total bilirubin ≤ 1.5 x ULN (or direct bilirubin below the ULN), AST and ALT ≤ 2.5 x ULN
   4. 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
   5. 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.
8. A female participant is eligible to participate if she is not pregnant (see Exclusion Criteria), not breastfeeding, and at least one of the following conditions applies:

   1. Not a woman of childbearing potential (WOCBP) as defined in the Appendix
   2. 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).
9. 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.
10. The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.

Exclusion Criteria:

Participants are excluded from the study if any of the following criteria apply:

1. Malignant pleural or pericardial effusion, based on clinical, imaging, or pathologic evaluation.
2. Systemic therapy for lung cancer within the past year.
3. 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).
4. Contraindication to protocol-specified radiotherapy, such as prior thoracic radiotherapy or active serious collagen vascular disease (e.g. scleroderma).
5. 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.
6. 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.
7. A history of (non-infectious) pneumonitis that required steroids or current pneumonitis.
8. Active infection requiring antimicrobial therapy.
9. Has a known history of active TB (Bacillus Tuberculosis).
10. 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

    the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
11. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
12. Pregnancy, assessed in WOCBP (defined in Appendix) with urine pregnancy test within 72 hours prior to study treatment allocation. If urine pregnancy test is positive or cannot be confirmed as negative, a serum pregnancy test is required. If more than 72 hours elapse between screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative.
13. For patients receiving pembrolizumab/radiotherapy

    1. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
    2. Ac

Trial Locations

• Montefiore Medical Center, The Bronx, New York, United States

Frequently Asked Questions

Related Conditions

• Non-small Cell Lung Cancer
• Lung Cancer
• Advanced Lung Cancer
• Stage II Lung Cancer
• Stage III Lung Cancer
• Immunotherapy
• Radiation Therapy
• PD-L1 Positive Cancer
• Oncology
• Thoracic Oncology

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