Lung Cancer, Malignant Pleural Effusion, Stage IV Metastatic Cancer
Conditions
Keywords
talimogene laherparepvec, Nivolumab, PleurX
Brief summary
This is a Phase Ib/II clinical trial to evaluate the feasibility of administering talimogene laherparepvec into the intrapleural space of subjects with malignant pleural effusion through a pleurX catheter.
Detailed description
This is a phase 1b/II clinical trial that includes a safety run-in cohort to investigate the novel approach of administering intrapleural talimogene laherparepvec via a pleurX catheter in patients with known malignant pleural effusion (MPE). In Phase Ib of this study, the safety of infusing talimogene laherparepvec directly into the pleural cavity of subjects diagnosed with MPE, through pleurX catheter, will be tested. In Phase II of this study, after establishing the safety of the above mentioned approach, 24 subjects will enrolled and treated with intrapleural talimogene laherparepvec and IV nivolumab.
Interventions
Talimogene laherparepvec (TVEC) (4ml of 108 pfu/ml) for up to 9 cycles, with or without nivolumab
DRUGNivolumab
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
Sponsors
C. R. Bard
Amgen
UNC Lineberger Comprehensive Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
We will conduct a Phase Ib/II trial that includes a safety run-in period using 3 +3 dose escalation rules to evaluate the feasibility of administering talimogene laherparepvec into the intrapleural space of subjects with malignant pleural effusion (MPE) via a pleurX catheter.
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
Patients must meet the following inclusion criteria to participate in this study: 1. Be ≥ 18 years of age on day of signing informed consent. 2. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 3. Histologically or cytologically confirmed stage IV metastatic cancer. 4. Confirmation of malignant pleural effusion via imaging (Computer tomography (CT) scan, chest x-ray (CXR), MRI, ultrasound, Positron Emission Tomography (PET)/CT), and cytology for which pleurX catheter placement is standard of care 5. Recovered from all reversible toxicities related to their previous treatment (other than alopecia) to ≤grade 1 or baseline; exceptions to this criterion may be allowed following review by the principal investigator for toxicities that are not expected to be exacerbated by nivolumab or talimogene laherparepvec. Grade 2 peripheral neuropathy will not result in exclusion as neither study agent would be expected to exacerbate it. 6. No history of untreated brain metastasis. Treated brain metastases must not be known to be progressive, symptomatic, or currently requiring \> 10 mg of prednisone or prednisone equivalents within two weeks prior to study drug administration. 7. Females of childbearing potential must have a negative serum pregnancy test within 72 hours prior to receiving the first dose of study medication. Females of childbearing potential must agree to use 2 methods of effective contraception or abstain from heterosexual sex throughout the treatment period and for 5 months after the last dose of study treatment. Females of childbearing potential are women who have not been surgically sterilized (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or have not been free of menses for \>1 year. 8. Male patients with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e. double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 7 months after the last dose of study treatment.
Exclusion criteria
Patients meeting any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase I Number of Participants With Treatment-related Adverse Events | from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks) | 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. |
| Phase II Resolution of MPE | 13 weeks | The rate of resolution of malignant pleural effusion following IV nivolumab combined with intrapleural injection of talimogene laherparepvec |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 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. |
| Median Progression Free Survival | 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. |
| Average Dyspnea Score | 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. |
| Phase II Number of Participants With Treatment-related Adverse Events | 13 weeks | 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. |
| Overall Survival | up to 2 years | Overall survival from day 1 of treatment until death |
Countries
United States
Participant flow
Recruitment details
Participants were recruited between March 2019 and August 2020.
Participants by arm
| Arm | Count |
|---|---|
| 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 | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Open-label, Single-arm Phase I |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 1 / 1 |
| other Total, other adverse events | 1 / 1 |
| serious Total, serious adverse events | 1 / 1 |
Outcome results
Primary
Phase II Resolution of MPE
The rate of resolution of malignant pleural effusion following IV nivolumab combined with intrapleural injection of talimogene laherparepvec
Time frame: 13 weeks
Population: No participants were enrolled on the Phase II portion of the study
Primary
Phase I Number of Participants With Treatment-related Adverse Events
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.
Time frame: from day 1 of treatment to 30 days after the last dose of study medication (approximately 11 weeks)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Open-label, Single-arm Phase I | Phase I Number of Participants With Treatment-related Adverse Events | 1 Participants |
Secondary
Average Dyspnea Score
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.
Time frame: 13 weeks
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label, Single-arm Phase I | Average Dyspnea Score | 4 score on a scale |
Secondary
Median Progression Free Survival
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.
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label, Single-arm Phase I | Median Progression Free Survival | 85 days |
Secondary
Overall Survival
Overall survival from day 1 of treatment until death
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label, Single-arm Phase I | Overall Survival | 85 days |
Secondary
Phase II Number of Participants With Treatment-related Adverse Events
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.
Time frame: 13 weeks
Population: No participants were enrolled in the Phase II portion of the study
Secondary
Response Rate
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.
Time frame: up to 2 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label, Single-arm Phase I | Response Rate | 0 proportion of participants |