Trial Outcomes & Findings for The Selective Personalized Radio-Immunotherapy for Locally Advanced NSCLC Trial (NCT NCT03523702)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

25 participants

Primary outcome timeframe

12 months

Results posted on

2024-12-03

Participant Flow

Patients were enrolled between August 2018 and November 2021.

Of the 42 patients who were consented into the trial, 5 were excluded prior to randomization. 4 of these patients did not meet inclusion/exclusion criteria and 1 was excluded based on personal reasons. Of these 37 patients, based on assay results, 25 patients were determined to have a PD-L1 tumor expression level of ≥ 50% and 12 patients were observed to have a PD-L1 tumor expression level of \< 50%. The 25 patients with a PD-L1 tumor expression level ≥ 50% were enrolled into the study.

Participant milestones

Participant milestones
Measure	PembroRT Cohort 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. 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. Subjects with PD-L1 expression \< 50%: Subjects with PD-L1 expression below 50% will be treated with concurrent chemoradiotherapy as part of standard of care and not enrolled into the study.
Overall Study STARTED	25
Overall Study COMPLETED	25
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	PembroRT Cohort n=25 Participants Subjects with PD-L1 expression ≥ 50% Combination of pembrolizumab and dose-painted radiotherapy for locally advanced NSCLC patients with high (≥ 50%) PD-L1 expression. 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.
Age, Continuous	70 years n=25 Participants
Sex: Female, Male Female	12 Participants n=25 Participants
Sex: Female, Male Male	13 Participants n=25 Participants
Region of Enrollment United States	25 participants n=25 Participants

PRIMARY outcome

Timeframe: 12 months

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.

Outcome measures

Outcome measures
Measure	PembroRT Cohort n=25 Participants 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. 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.
Progression-Free Survival (PFS)	19 Participants

SECONDARY outcome

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

To characterize freedom from distant metastases following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%, cumulative incidence was calculated treating other events as competing risks. Competing risks are those events which prevent the occurrence or modify the risk of the outcome of distant metastasis. For this study, cumulative incidence is defined as the percentage of patients free from distant metastases up to 18 months following completion of treatment / number of people at risk in the study population and is reported as a percentage.

Outcome measures

Outcome measures
Measure	PembroRT Cohort n=25 Participants 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. 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.
Freedom From Distant Metastasis	17 Participants

SECONDARY outcome

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

To characterize freedom from intrathoracic disease progression rates following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50%, the cumulative incidence rate will be determined using competing risk analysis. For this study, intrathoracic disease progression will be reported as a percentage of patients.

Outcome measures

Outcome measures
Measure	PembroRT Cohort n=25 Participants 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. 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.
Intrathoracic Disease Progression	22 Participants

SECONDARY outcome

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

Overall survival (OS) of patients alive at 1 year and 2 years following treatment with sequential pembrolizumab and radiotherapy for locally advanced NSCLC with PD-L1 expression ≥ 50% was analyzed. OS was defined as the percentage of treated participants who were still alive at 1 year or 2 years following completion of treatment, divided by the total number of treated participants, multiplied by 100. Overall survival was censored at the time of the last clinic visit or contact.

Outcome measures

Outcome measures
Measure	PembroRT Cohort n=25 Participants 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. 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.
Overall Survival (OS) 1-year Overall Survival	23 Participants
Overall Survival (OS) 2-year Overall Survival	19 Participants

SECONDARY outcome

Timeframe: 2 months

Radiographic Response will be scored using RECIST V1.1 criteria to quantify objective measures of change in tumor burden. Although RECIST 1.1 references a maximum of 5 target lesions in total and 2 per organ, the Sponsor allows a maximum of 10 target lesions in total and 5 per organ, if clinically relevant to enable a broader sampling of tumor burden. RECIST will be used to quantify the percentage of patients demonstrating Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD), as follows: CR - resolution of all target lesions to background levels PR - at least 30% decrease in sum of diameters of target lesions (noting baseline diameters) SD - neither sufficient shrinkage to qualify for PR or sufficient increase to qualify for PD (noting smallest sum on study) PD - at least 20% increase in sum of diameters of target lesions (noting smallest sum on study); absolute increase of 5mm must be demonstrated; \>=1 new lesion is considered PD

Outcome measures

Outcome measures
Measure	PembroRT Cohort n=25 Participants 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. 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.
Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Complete Response (CR)	1 Participants
Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Partial Response (PR)	11 Participants
Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Stable Disease (SD)	11 Participants
Radiographic Response Rate Based on Response Evaluation Criteria in Solid Tumors (RECIST) Progressive Disease (PD)	2 Participants

SECONDARY outcome

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

Population: Unplanned hospitalization data was not collected.

The unplanned hospitalization rate will be determined as the percentage of participants hospitalized due to treatment-related toxicities.

Outcome measures

Outcome data not reported

Adverse Events

PembroRT Cohort

Serious events: 0 serious events

Other events: 10 other events

Deaths: 6 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	PembroRT Cohort n=25 participants at risk 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. 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.
Blood and lymphatic system disorders Anemia	12.0% 3/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.
Musculoskeletal and connective tissue disorders Arthritis	8.0% 2/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.
Gastrointestinal disorders Diarrhea/Colitis	24.0% 6/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.
Gastrointestinal disorders Esophagitis	40.0% 10/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.
Respiratory, thoracic and mediastinal disorders Pneumonitis	12.0% 3/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.
Investigations Weight Loss	8.0% 2/25 • Patients were monitored for adverse events for up to 18 months following treatment for a total of up to 30 months.

Additional Information

Dr. Nitin Ohri

Albert Einstein College of Medicine

Phone: 718-920-7750

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place