Trial Outcomes & Findings for Trial of pIL-12/MK-3475 in Metastatic Melanoma (NCT NCT02493361)

Last Updated: 2021-01-06

Results Overview

Best overall ORR within 24 weeks of first treatment with pIL-12 electroporation (EP) and pembrolizumab will be determined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions and assessed by CT or MRI. The ORR is the proportion of participants with either a Complete Response (CR) defined as a disappearance of all target lesions determined by 2 separate scans conducted not \< 4 weeks apart and any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm (the sum may not be "0" if there are target nodes) and no appearance of new lesions or a Partial Response (PR) defined as a \>=30% decrease in the sum of the longest diameter of target lesions with no appearance of new lesions. ORR = CR + PR.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

24 participants

Primary outcome timeframe

Up to week 24

Results posted on

2021-01-06

Participant Flow

Participant milestones

Participant milestones
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Overall Study STARTED	24
Overall Study Week 24 Assessment	21
Overall Study COMPLETED	21
Overall Study NOT COMPLETED	3

Reasons for withdrawal

Reasons for withdrawal
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Overall Study Withdrawal by Subject	3

Baseline Characteristics

Trial of pIL-12/MK-3475 in Metastatic Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Age, Continuous	65.5 years STANDARD_DEVIATION 11.9 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	14 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	22 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 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	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	3 Participants n=5 Participants
Region of Enrollment United States	24 participants n=5 Participants

PRIMARY outcome

Timeframe: Up to week 24

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Best Overall Objective Response Rate (ORR) Within 24 Weeks Using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	0.375 proportion of participants

SECONDARY outcome

Timeframe: Up to 5 years

Best overall objective response rate is defined as the proportion of participants with a demonstrated complete or partial response according to irRC. In the irRC, an immune-related Complete Response (irCR) is the disappearance of all lesions, measured or unmeasured, and no new lesions; an immune-related Partial Response (irPR) is a 50% drop in tumour burden from baseline as defined by the irRC.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=21 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Best Overall ORR Determined by Immune Related-Response Criteria (irRC)	.429 proportion of participants

SECONDARY outcome

Timeframe: At 24 weeks after treatment initiation

Twenty-four week landmark PFS (PFS at 24) is defined as the percentage of patients, who have progressed at the 24 week time point (+ / - 2 days visit tolerance). Tumor response determinations were assessed by RECIST v1.1.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=21 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Twenty-Four Week Landmark Progression Free Survival (PFS)	170 days Interval 86.0 to 170.0

SECONDARY outcome

Timeframe: Up to 2 years

The study will use the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0 with an adverse or serious adverse event determination of possible, probable, or definite attribution. Analyses will be performed for all patients having received at least one dose of study drug.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Number of Participants With Treatment-related Adverse Events	2 Participants

SECONDARY outcome

Timeframe: Up to 5 years

PFS is defined as the duration between the date of treatment initiation to the first date of either disease progression where progression is assessed by RECIST v1.1, or death.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=21 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Median PFS	253 days Interval 86.0 to 1659.0

SECONDARY outcome

Timeframe: Up to 5 years

DOR is defined as the number of days from the initial documentation of an objective response (CR or PR) per RECIST v1.1 criteria to the final evaluation of that response (censored duration), or to documentation of progression using Kaplan-Meier (KM) estimates .

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=9 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Duration of Response (DOR) Estimate	NA months Of the 9 participants with an objective response (CR or PR), 0 patients progressed after achieving an objective response and therefore all of the durations were censored. As a result, the KM estimates are not calculable.

SECONDARY outcome

Timeframe: Up to 5 years

OS is defined as the duration between the date of treatment initiation to the date of death, regardless of the cause of death using KM estimates.

Outcome measures

Outcome measures
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 Participants Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Overall Survival (OS) Estimate	NA days The KM estimate could not be calculated given that 82% of the subjects were still alive at the time of the last follow-up and over 80% of the OS durations were censored.

Adverse Events

Pembrolizumab and Intratumoral pIL-12 Electroporation

Serious events: 3 serious events

Other events: 24 other events

Deaths: 4 deaths

Serious adverse events

Serious adverse events
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 participants at risk Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Infections and infestations Skin infection	4.2% 1/24 • Number of events 1 • Up to 5 years
Cardiac disorders Myocardial infarction	4.2% 1/24 • Number of events 1 • Up to 5 years
Hepatobiliary disorders Hepatobiliary disorders - Other	4.2% 1/24 • Number of events 1 • Up to 5 years
General disorders Pain	4.2% 1/24 • Number of events 1 • Up to 5 years
Cardiac disorders Acute coronary syndrome	4.2% 1/24 • Number of events 1 • Up to 5 years

Other adverse events

Other adverse events
Measure	Pembrolizumab and Intratumoral pIL-12 Electroporation n=24 participants at risk Treatments of pembrolizumab and pIL-12 were given in three week cycles that repeated as long as there was benefit, for up to 24 months or until disease worsened. Some subjects had the option of continuing treatment beyond 24 months or after worsening of disease under limited circumstances. Pembrolizumab: 200 mg dose is given intravenously, Day 1 of each cycle. pIL-12: Given by injection into the tumor at 1/4 tumor volume at concentration of 0.5 mg/mL, Days 1, 5, and 8 of each odd numbered cycle.
Blood and lymphatic system disorders Anemia	8.3% 2/24 • Number of events 2 • Up to 5 years
Musculoskeletal and connective tissue disorders Arthralgia	20.8% 5/24 • Number of events 5 • Up to 5 years
Investigations Aspartate aminotransferase increased	8.3% 2/24 • Number of events 2 • Up to 5 years
Investigations Alkaline phosphatase increased	8.3% 2/24 • Number of events 2 • Up to 5 years
Investigations Creatinine increased	12.5% 3/24 • Number of events 3 • Up to 5 years
Investigations Lactate dehydrogenase increased	8.3% 2/24 • Number of events 2 • Up to 5 years
Investigations Thyroid stimulating hormone increased	8.3% 2/24 • Number of events 2 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Upper respiratory infection	8.3% 2/24 • Number of events 2 • Up to 5 years
Gastrointestinal disorders Constipation	20.8% 5/24 • Number of events 5 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Cough	16.7% 4/24 • Number of events 4 • Up to 5 years
Metabolism and nutrition disorders Anorexia	12.5% 3/24 • Number of events 3 • Up to 5 years
Psychiatric disorders Depression	8.3% 2/24 • Number of events 2 • Up to 5 years
Gastrointestinal disorders Diarrhea	16.7% 4/24 • Number of events 4 • Up to 5 years
Nervous system disorders Dizziness	37.5% 9/24 • Number of events 9 • Up to 5 years
General disorders Fatigue	70.8% 17/24 • Number of events 17 • Up to 5 years
General disorders Fall	12.5% 3/24 • Number of events 3 • Up to 5 years
Nervous system disorders Headache	20.8% 5/24 • Number of events 5 • Up to 5 years
Nervous system disorders Hypoesthesia	12.5% 3/24 • Number of events 3 • Up to 5 years
General disorders Flu like symptoms	8.3% 2/24 • Number of events 2 • Up to 5 years
Injury, poisoning and procedural complications Injection site pain	12.5% 3/24 • Number of events 3 • Up to 5 years
Psychiatric disorders Insomnia	8.3% 2/24 • Number of events 2 • Up to 5 years
Musculoskeletal and connective tissue disorders Muscle spasm	8.3% 2/24 • Number of events 2 • Up to 5 years
Musculoskeletal and connective tissue disorders Myalgia	20.8% 5/24 • Number of events 5 • Up to 5 years
Respiratory, thoracic and mediastinal disorders Nasal congestion	12.5% 3/24 • Number of events 3 • Up to 5 years
Gastrointestinal disorders Nausea	33.3% 8/24 • Number of events 8 • Up to 5 years
General disorders Peripheral edema	20.8% 5/24 • Number of events 5 • Up to 5 years
Injury, poisoning and procedural complications Procedural pain	54.2% 13/24 • Number of events 13 • Up to 5 years
Skin and subcutaneous tissue disorders Pruritus	33.3% 8/24 • Number of events 8 • Up to 5 years
General disorders Fever	8.3% 2/24 • Number of events 2 • Up to 5 years
Skin and subcutaneous tissue disorders Rash	8.3% 2/24 • Number of events 2 • Up to 5 years
Skin and subcutaneous tissue disorders Rash pruritic	29.2% 7/24 • Number of events 7 • Up to 5 years
Infections and infestations Sinusitis	8.3% 2/24 • Number of events 2 • Up to 5 years
Nervous system disorders Tremor	8.3% 2/24 • Number of events 2 • Up to 5 years
Eye disorders Blurred vision	12.5% 3/24 • Number of events 3 • Up to 5 years
Gastrointestinal disorders Vomiting	8.3% 2/24 • Number of events 2 • Up to 5 years
Investigations Weight loss	8.3% 2/24 • Number of events 2 • Up to 5 years
Blood and lymphatic system disorders Hematocrit decreased	8.3% 2/24 • Number of events 2 • Up to 5 years

Additional Information

Dr. Katy Tsai

University of California, San Francisco

Phone: (415) 402-5483

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: LTE60