Trial Outcomes & Findings for A Study of Nivolumab and Intrapleural Talimogene Laherparepvec for Malignant Pleural Effusion (NCT NCT03597009)

Last Updated: 2021-04-20

Results Overview

Number of participants with treatment-related adverse events as assessed by the NCI Common Terminology Criteria for Adverse Events which is a descriptive terminology which can be utilized for Adverse Event (AE) reporting. A grading (severity) scale is provided for each AE term. Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental Activities of Daily Living (ADL). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE.

Recruitment status

TERMINATED

Study phase

PHASE1/PHASE2

Target enrollment

1 participants

Primary outcome timeframe

from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)

Results posted on

2021-04-20

Participant Flow

Participants were recruited between March 2019 and August 2020.

Participant milestones

Participant milestones
Measure	Open-label, Single-arm Phase I Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Overall Study STARTED	1
Overall Study COMPLETED	1
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Study of Nivolumab and Intrapleural Talimogene Laherparepvec for Malignant Pleural Effusion

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants
Sex: Female, Male Male	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	1 participants n=5 Participants

PRIMARY outcome

Timeframe: from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)

Outcome measures

Outcome measures
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Phase I Number of Participants With Treatment-related Adverse Events	1 Participants

PRIMARY outcome

Timeframe: 13 weeks

Population: No participants were enrolled on the Phase II portion of the study

The rate of resolution of malignant pleural effusion following IV nivolumab combined with intrapleural injection of talimogene laherparepvec

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: up to 2 years

Progression free survival from day 1 of treatment until death or progression. Per immune-related Response Evaluation Criteria in Solid Tumours (irRECIST), immune-related Progressive Disease (irPD)is defined as at least 20% and minimum 5 mm absolute increase in total measured tumor burden compared to nadir, or irPD for non-target or new un-measurable lesions.

Outcome measures

Outcome measures
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Median Progression Free Survival	85 days

SECONDARY outcome

Timeframe: up to 2 years

Overall survival from day 1 of treatment until death

Outcome measures

Outcome measures
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Overall Survival	85 days

SECONDARY outcome

Timeframe: up to 2 years

Response rate after treatment per Immune-Related Response Evaluation Criteria In Solid Tumors (irRECIST) defined as the proportion of patients with reduction in tumor (immune-related Complete Response (irCR) or immune-related Partial Response (irPR)). irCR is a complete disappearance of all lesions (whether measurable or not) and no new lesions. Lymph nodes must decrease to \<10mm in short axis. irPR is a decrease in tumor burden ≥ 30%, in total measured tumor burden relative to baseline, non-target lesions are not in complete response (disappearance of all lesions) and not unequivocal progression or new non-measurable lesions.

Outcome measures

Outcome measures
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Response Rate	0 proportion of participants

SECONDARY outcome

Timeframe: 13 weeks

Population: No participants were enrolled in the Phase II portion of the study

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 13 weeks

Results from patient reports of the Modified Borg Scale of Perceived Dyspnea, measuring change in scale over time. The scale evaluates perceived level of shortness of breath ranging from 0 to 10, where 0 indicates the greatest success of the treatment.

Outcome measures

Outcome measures
Measure	Open-label, Single-arm Phase I n=1 Participants Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Average Dyspnea Score	4 score on a scale

Adverse Events

Open-label, Single-arm Phase I

Serious events: 1 serious events

Other events: 1 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	Open-label, Single-arm Phase I n=1 participants at risk Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Infections and infestations Sepsis	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)

Other adverse events

Other adverse events
Measure	Open-label, Single-arm Phase I n=1 participants at risk Talimogene laherparepvec (TVEC) administered into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter with or without nivolumab Talimogene laherparepvec (TVEC): Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab Nivolumab: Nivolumab (240 mg IV) will be co-administered with talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles in the Dose Level 2 cohort
Investigations Alkaline phosphatase increased	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Blood and lymphatic system disorders Anemia	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Investigations Aspartate aminotransferase increased	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Musculoskeletal and connective tissue disorders Bone pain	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
General disorders Fever	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Metabolism and nutrition disorders Hypoalbuminemia	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Metabolism and nutrition disorders Hypomagnesemia	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)
Metabolism and nutrition disorders Hypophosphatemia	100.0% 1/1 • From day one of treatment to 30 days after the last dose of treatment (approximately 11 weeks)

Additional Information

Robin Johnson

University of North Carolina Lineberger Comprehensive Cancer Center

Phone: 919-966-1125

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place