Trial Outcomes & Findings for Trial of Consolidation Pembrolizumab After Concurrent Chemotherapy and Proton Reirradiation for Thoracic Recurrences of Non-Small Cell Lung Cancer (NCT NCT03087760)

Last Updated: 2024-01-18

Results Overview

Progression Free Survival is defined as the time from initiation of definitive therapy to the first documented disease progression per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 based on radiologists' review or death due to any cause, whichever occurs first, or last patient follow-up that documented lack of disease progression. Patients who have not had disease progression or who have died, will be censored on the most recent clinical evaluation date that documented that they were progression-free.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

32 participants

Primary outcome timeframe

2 years

Results posted on

2024-01-18

Participant Flow

Between November 2017 and April 2021, 32 patients were consented and reviewed for eligibility, of which 10 were excluded. Most common reasons for exclusion were internal clinical target volume (iCTV) ≥250 cc on the simulation scan (n = 3), histology other than non-small cell lung cancer (NSCLC) (n = 3), and extrathoracic metastases (n = 2). Twenty-two patients initiated proton beam therapy (PBT) reirradiation (reRT) on-trial and were included in the intention-to-treat analysis.

Participant milestones

Participant milestones
Measure	Single Arm Single Arm, Open Label Pembrolizumab 100 mg/4mL (dosage form: solution for injection). Pembrolizumab will be administered as a 30 minute intravenous infusion. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Concurrent Pembrolizumab after proton reirradiation.
Overall Study STARTED	22
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	19

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

15 out 22 participants had prior overlapping radiation therapy - definitive chemoradiation.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Single Arm n=22 Participants Single Arm, Open Label Pembrolizumab: Concurrent Pembrolizumab after proton reirradiation
Age, Categorical <=18 years	0 Participants n=22 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=22 Participants
Age, Categorical >=65 years	14 Participants n=22 Participants
Age, Continuous	68 years n=22 Participants
Sex: Female, Male Female	11 Participants n=22 Participants
Sex: Female, Male Male	11 Participants n=22 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=22 Participants
Race (NIH/OMB) Asian	0 Participants n=22 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=22 Participants
Race (NIH/OMB) Black or African American	2 Participants n=22 Participants
Race (NIH/OMB) White	18 Participants n=22 Participants
Race (NIH/OMB) More than one race	1 Participants n=22 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=22 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Eastern Cooperative Oncology Group (ECOG) performance status: 0	7 Participants n=22 Participants
Eastern Cooperative Oncology Group (ECOG) performance status Eastern Cooperative Oncology Group (ECOG) performance status: 1	15 Participants n=22 Participants
Histology Adenocarcinoma	12 Participants n=22 Participants
Histology Squamous cell carcinoma	8 Participants n=22 Participants
Histology Adenosquamous	1 Participants n=22 Participants
Histology Non-small cell lung cancer (NSCLC), not otherwise specified	1 Participants n=22 Participants
Programmed death-ligand (PD-L1 ) <1%	9 Participants n=22 Participants
Programmed death-ligand (PD-L1 ) 1-50%	9 Participants n=22 Participants
Programmed death-ligand (PD-L1 ) >50%	3 Participants n=22 Participants
Programmed death-ligand (PD-L1 ) Not Applicable (N/A)	1 Participants n=22 Participants
Epidermal growth factor receptor (EGFR) mutation	1 Participants n=22 Participants
Anaplastic lymphoma kinase (ALK) translocation	1 Participants n=22 Participants
Recurrence location Primary tumor	4 Participants n=22 Participants
Recurrence location Nodal	8 Participants n=22 Participants
Recurrence location Primary tumor + nodal	10 Participants n=22 Participants
Prior overlapping radiation therapy - Definitive chemoradiation Intensity modulated radiation therapy (IMRT)	11 Participants n=15 Participants • 15 out 22 participants had prior overlapping radiation therapy - definitive chemoradiation.
Prior overlapping radiation therapy - Definitive chemoradiation Passive scatter proton beam therapy (PBT)	2 Participants n=15 Participants • 15 out 22 participants had prior overlapping radiation therapy - definitive chemoradiation.
Prior overlapping radiation therapy - Definitive chemoradiation Pencil beam scanning proton beam therapy (PBT)	2 Participants n=15 Participants • 15 out 22 participants had prior overlapping radiation therapy - definitive chemoradiation.
Prior overlapping radiation therapy - Stereotactic body radiation therapy (SBRT)	3 Participants n=22 Participants
Prior overlapping radiation therapy - Pre-operative chemoradiation (IMRT)	1 Participants n=22 Participants
Prior overlapping radiation therapy - Post-operative chemoradiation (3D-CRT)	1 Participants n=22 Participants
Prior overlapping radiation therapy - Definitive chemoradiation (passive scatter PBT) and SBRT	1 Participants n=22 Participants
Prior overlapping radiation therapy - Pre-operative (IMRT) and post-operative (IMRT) chemoradiation	1 Participants n=22 Participants
Prior surgery for lung cancer Lobectomy	6 Participants n=8 Participants • 8 out of the 22 analyzed participants had prior surgery for lung cancer.
Prior surgery for lung cancer Wedge resection	2 Participants n=8 Participants • 8 out of the 22 analyzed participants had prior surgery for lung cancer.
Prior consolidation durvalumab	8 Participants n=22 Participants
Prior consolidation durvalumab - Median duration	12 months n=22 Participants

PRIMARY outcome

Timeframe: 2 years

Outcome measures

Outcome measures
Measure	Single Arm n=22 Participants Single Arm, Open Label Pembrolizumab: Concurrent Pembrolizumab after proton reirradiation
Number of Subjects With Progression Free Survival	6 Participants

SECONDARY outcome

Timeframe: 2 years

Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0. Adverse events were reviewed by the treating physicians and principal investigator to assess potential attribution to reirradiation/chemotherapy or pembrolizumab.

Outcome measures

Outcome measures
Measure	Single Arm n=22 Participants Single Arm, Open Label Pembrolizumab: Concurrent Pembrolizumab after proton reirradiation
Number of Participants Who Experienced a Grade 3+ Adverse Event	10 Participants

Adverse Events

Single Arm

Serious events: 10 serious events

Other events: 16 other events

Deaths: 14 deaths

Serious adverse events

Serious adverse events
Measure	Single Arm n=22 participants at risk Single Arm, Open Label Pembrolizumab 100 mg/4mL (dosage form: solution for injection). Pembrolizumab will be administered as a 30 minute intravenous infusion. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Concurrent Pembrolizumab after proton reirradiation.
Respiratory, thoracic and mediastinal disorders Hemoptysis	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Respiratory, thoracic and mediastinal disorders Pneumonitis	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Esophagitis	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Injury, poisoning and procedural complications Tracheal rupture	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Aorto-esophageal fistula	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Respiratory, thoracic and mediastinal disorders Recurrent Laryngeal Nerve Damage	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Immune system disorders Anaphylaxis	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Oral mucositis and lichenoid dermatitis	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Neutropenia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Lymphopenia	22.7% 5/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.

Other adverse events

Other adverse events
Measure	Single Arm n=22 participants at risk Single Arm, Open Label Pembrolizumab 100 mg/4mL (dosage form: solution for injection). Pembrolizumab will be administered as a 30 minute intravenous infusion. Sites should make every effort to target infusion timing to be as close to 30 minutes as possible. However, given the variability of infusion pumps from site to site, a window of -5 minutes and +10 minutes is permitted (i.e., infusion time is 30 minutes: -5 min/+10 min). Concurrent Pembrolizumab after proton reirradiation.
Respiratory, thoracic and mediastinal disorders Pneumonitis	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Esophagitis	36.4% 8/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Anorexia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Respiratory, thoracic and mediastinal disorders Cough	18.2% 4/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
General disorders Fatigue	36.4% 8/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Respiratory, thoracic and mediastinal disorders Dyspnea	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Musculoskeletal and connective tissue disorders Weakness	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Gastroesopheal reflux	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Respiratory, thoracic and mediastinal disorders Pleural effusion	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
General disorders Leg edema	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Musculoskeletal and connective tissue disorders Myalgia or arthralgia	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Elevated BUN	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Anemia	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hyperglycemia	13.6% 3/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hyponatremia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Endocrine disorders Hyperthyroidism	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hypomagnesemia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Thrombocytopenia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Nausea	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hypokalemia	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hypoalbuminemia	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Investigations Elevated creatinine	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Nervous system disorders Neuropathy	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Musculoskeletal and connective tissue disorders Muscle cramps	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Skin and subcutaneous tissue disorders Pruritus	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Nervous system disorders Headache	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Constipation	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Nervous system disorders Dizziness	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Gastrointestinal disorders Diarrhea	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Nervous system disorders Dysgeusia	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Skin and subcutaneous tissue disorders Rash	4.5% 1/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Blood and lymphatic system disorders Lymphopenia	22.7% 5/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Endocrine disorders Hypothyroidism	22.7% 5/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.
Metabolism and nutrition disorders Hypercalcemia	9.1% 2/22 • Adverse events will be monitored during Pembrolizumab treatment and for one year following treatment for patients who completed all 17 cycles of Pembrolizumab, up to 2 years.

Additional Information

Ching Lai

University of Pennsylvania

Phone: 267-250-9244

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place