This is a single-arm, open label, Phase II study evaluating the safety and efficacy of neoadjuvant Nivolumab and HF10 in resectable stage IIIB, IIIC, and IVM1a melanoma.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
7
Nivolumab at a dose of 240 mg given as an IV infusion starting on day 0. It will be given every 14 days for a total of 7 infusions; Then participant will undergo surgery. Nivolumab will then be administered at a flat dose of 480 mg IV every 28 days for up to one year.
1 x 107th TCID50/mL, intratumoral injection to a single or multiple eligible tumors for a total of 5 mL; on days 0, 7, 14, 21, 28, 42, 56, 70, 84 for a total of 9 injections. All eligible tumors except one will be treated with HF10 up to the maximum volume allowed. The untreated tumor will be used as an untreated control lesion.
Huntsman Cancer Institute
Salt Lake City, Utah, United States
Pathological Response
Following 12 weeks of neoadjuvant treatment with nivolumab and HF10, participants underwent definitive surgery. A percent viable tumor was assessed semi-quantitatively in the definitive surgical resection specimen by estimating the proportion of residual tumor in relation to the total tumor area and reported as percentage viability. A pathologic complete response was defined as no viable residual melanoma cells in the surgical specimen. A major pathologic response was defined as \<50% viable tumor cells. A minor pathologic response was defined as 50% or greater viable tumor cells, including specimens that had 100% viability at surgery.
Time frame: at time of surgery (12 weeks)
Recurrence-free Survival: Number of Participants With no Disease Recurrence After Surgery
Recurrence after surgery will be assessed by radiologic scans and confirmed by biopsy. Death within the follow-up period is also considered recurrence. This outcome will report the number of participants who were alive and who had no disease recurrence during the follow-up period.
Time frame: up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)
Overall Survival: Number of Participants Alive One Year After Completing Adjuvant Nivolumab
Participants were followed for survival for one year after completion of adjuvant nivolumab. Adjuvant nivolumab was planned for up to one year of adjuvant treatment after surgery. This objective reports the number of participants who were alive one year after the completion of adjuvant nivolumab.
Time frame: up to 2 years post-surgery (1 year after end of adjuvant nivolumab, which was given for up to 1 year post-surgery)
Radiographic Response: Number of Participants Within Each Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Response Category
Participants were assessed radiographically and clinically prior to study start and prior to surgery. Lesions were measured, and lesions that were at least 10 mm on CT, MRI, caliper, or ruler, or at least 20 mm on x-ray were documented as Target Lesions. Lesions that did not meet criteria to be Target Lesions were documented as Non-Target lesions. Measurements of Target Lesions were summed. Change in Target Lesion measurements was used to determine response by RECIST 1.1 criteria. Complete Response (CR) indicates a disappearance of all lesions. Partial Response (PR) indicates at least 30% decrease in the sum of Target Lesions. Progressive Disease (PD) indicates at least 20% increase in the sum of Target Lesions, or the appearance of one or more new lesions after baseline. Stable Disease (SD) is neither sufficient shrinkage to qualify as PR nor sufficient increase to qualify as PD. Objective was reported as number of participants within each response category.
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Time frame: 12 weeks from baseline to surgery
Number of Participants With Complete Surgical Resection
Participants' surgical samples were assessed by a pathologist after surgery to determine if complete surgical resection was achieved after neo-adjuvant treatment with nivolumab and HF10. R0 indicates a complete surgical resection was achieved and means no residual tumor was detected after after surgery. R1 means microscopic tumor was detected and a complete surgical resection was not achieved.
Time frame: Within 28 days after Day 84
Number of Participants With Adverse Events Related to HF10 Treatment
Participants were monitored for adverse events (AEs) during treatment with HF10 using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to HF10 treatment are grouped by grade 1-2 and grade 3-5 AEs.
Time frame: throughout HF10 treatment (up to 84 days)
Number of Participants With Adverse Events Related to Nivolumab Treatment
Participants were monitored for adverse events (AEs) during treatment with nivolumab using CTCAE v4 criteria. AEs were graded as being mild (grade 1), moderate (grade 2), grade 3 (severe), grade 4 (life-threatening), and grade 5 (fatal). Each adverse event was reviewed by a treating investigator for relatedness to study treatment. For this outcome, the number of participants who experienced any AEs that were possible, probably, or definitely related to nivolumab treatment are grouped by grade 1-2 and grade 3-5 AEs.
Time frame: throughout nivolumab treatment (up to 84 days prior to surgery and up to 1 year after surgery)