PV-10 vs Chemotherapy or Oncolytic Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

PFS was estimated via Kaplan-Meier analysis using Response Evaluation Criteria In Solid Tumors (RECIST v1.1) criteria. Subjects who did not have an event of progression or death were censored at their last assessment date. Assessment of progression was performed by the sponsor based on review of lesion measurement and clinical progression data reported by each investigator. Events signaling progression included increase in size and/or number of study lesions, onset of visceral metastatic disease, and death. For target lesions (assigned prior to randomization), complete response (CR) required disappearance of all target lesions; partial response (PR) required \>= 30% decrease in sum of the longest diameter (SLD) of all target lesions; progressive disease (PD) required \>=20% increase in SLD of target lesions. Non-target lesions were followed for CR, PD, or non-CR/non-PD status using equivalent thresholds. Progression occurred when PD was observed in either target or non-target lesion.

Time frame: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; progression detected between formal assessments was documented at the time of detection; median follow-up time for PFS was 26.6 weeks, maximum was 125.8 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are not included in the analysis population.~Response data from one study center were censored due to resignation of the principal investigator.~Because the study was terminated prior to achievement of pre-specified efficacy thresholds (i.e., out of a planned 225 subjects only 20 initiated study treatment), the small number of subjects enrolled precludes scientifically meaningful interpretation of PFS.

CRR was assessed using RECIST v1.1 criteria, and required disappearance of all target and non-target lesions.

Time frame: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for CRR was 26.6 weeks, maximum was 125.8 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are not included in the analysis population.~Response data from one study center were censored due to resignation of the principal investigator.~Because the study was terminated prior to achievement of pre-specified efficacy thresholds (i.e., out of a planned 225 subjects only 20 initiated study treatment), the small number of subjects enrolled precludes scientifically meaningful interpretation of CRR.

DCR was estimated via Kaplan-Meier analysis for participants achieving a complete response, and was defined as the interval from first complete response to disease progression or death; responders who did not have an event of progression or death were censored at their last assessment date. Complete response was assessed using RECIST v1.1 criteria, and required disappearance of all target and non-target lesions.

Time frame: Assessed every 12 weeks until disease progression, withdrawal of consent, or study termination; median follow-up time for DCR was 26.7 weeks, maximum was 77.7 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are not included in the analysis population.~Response data from one study center were censored due to resignation of the principal investigator.

Safety and tolerability were assessed by monitoring the frequency, duration, severity and attribution of adverse events and evaluating changes in laboratory values and vital signs.

Time frame: Assessed every 4 weeks until 28 days after last treatment; median duration of treatment was 11.8 and 9.5 weeks in each treatment group, respectively.

Population: PV-10 safety population includes two subjects who received PV-10 upon crossover after progression on comparator.

OS was documented at 12 week intervals commencing on withdrawal from active study participation. Documentation was made by subject clinic visit or other personal contact, telephonic contact, review of medical records, or other unequivocal evidence of survival status. OS was estimated via Kaplan-Meier analysis, and was defined as the interval from randomization to death; subjects who did not have an event of death were censored at their last assessment date.

Time frame: Assessed every 12 weeks upon withdrawal from active study participation until death, withdrawal of consent, or study termination; median follow-up time for survival was 82.4 weeks, maximum was 167.0 weeks.

Population: Subjects were analyzed according to treatment group assignment at randomization.

In this exploratory endpoint, changes in Skindex-16 self-assessment scores were evaluated vs Day 1 baseline domain scores: symptom domain (items 1-4); emotional domain (items 5-11); and functioning domain (items 12-16). The Skindex-16 instrument solicits response to the extent of bother during the preceding week by 16 items (e.g., itching, hurting, worry, impact on daily activities), using a score from 0 (never bothered) to 6 (always bothered) for each item. Item scores are transformed to 0 to 100 scale, and domain scores are calculated as the average of the item scores comprising the domain. A lower domain score at baseline signifies lower impact of that domain; a decrease in domain score from baseline signifies improvement in that domain. Median baseline score and change from baseline over the study interval is presented for each domain.

Time frame: Assessed at baseline (Day 1 at start of study treatment) and at the end of each treatment cycle (every 4 or 6 weeks) until disease progression, withdrawal of consent, or study termination; median follow-up time was 26.6 weeks, maximum was 125.8 weeks.

Population: Subjects receiving PV-10 upon crossover from comparator are included in the analysis population for PV-10 (after crossover).~Response data from one study center were censored due to resignation of the principal investigator.~Because the study was terminated prior to achievement of pre-specified efficacy thresholds (i.e., out of a planned 225 subjects only 20 initiated study treatment), the small number of subjects enrolled precludes scientifically meaningful interpretation of Skindex data.