Table 1

Patient characteristics and treatment response

ID	Baseline demography						PVSRIPO Tx	Poststudy Follow-up
ID	Baseline stage	BRAF status at screening	Prior therapies (last to most recent)	Total lesions (n)	Timing of last anti-PD-1 Tx relative to PVSRIPO injection (days)	Anti-PD-1 resistance*	irRC†	Additional therapies after PVSRIPO	Progression-free during follow-up Tx?	Time since first PVSRIPO injection
Cohort 0: single lesion injected at baseline/day 0
1	IV, M1a	WT	Nivolumab and T-VEC	>5	~213 days	Primary	NA‡	Ipilimumab/nivolumab and maintenance nivolumab	Yes§	25 months
2	IV, M1b	WT	Pembrolizumab, T-VEC, ipilimumab/nivolumab, investigational agent, and pembrolizumab	5	44 days	Primary	NA‡	Pembrolizumab, radiation, and binimetinib	No	23 months (died of disease)
3	IIIC	Mut	Vemurafenib and ipilimumab/nivolumab	3	~100 days	Inadequate exposure¶	NA‡	Ipilimumab/nivolumab and maintenance nivolumab, radiation, T-VEC, investigational agent plus pembrolizumab	No	20 months (died of disease)
Cohort 1: two total lesions injected (one at baseline/day 0 and one on day 21)
4	IV, M1a	Mut	>10 therapies, including encorafenib/binimetinib, pembrolizumab, IL-2, and T-VEC	>5	~400 days	Secondary	NA‡	Encorafenib, investigational agent plus pembrolizumab, binimetinib, and abraxane	No	22 months (died of disease)
5	IIIC	Mut	Pembrolizumab, T-VEC, investigational agent/pembro, dabrafenib/trametinib, vemurafenib/cobimetinib, and encorafenib/binimetinib	>5	~456 days	Secondary	NA‡	Pembrolizumab	Yes	20 months
6	IIIC	WT	Nivolumab, T-VEC, ipilimumab/ nivolumab, and radiation	>5	~213 days	Primary	NA‡	Nivolumab and investigational agent	No	11 months (died of disease)
Cohort 2: three total lesions injected (one at baseline/day 0, one on day 21, and one on day 42)
7	IV, M1b	WT	Ipilimumab/nivolumab, investigational agent/pembrolizumab	>5	30 days	Secondary	NA‡	Pembrolizumab and T-VEC	No	9 months (died of disease)
8	IV, M1a	WT	Nivolumab and pembrolizumab	4	26 days	Primary	irPR**	Pembrolizumab	Yes	17 months
9	IIIC	WT	Nivolumab	>5	15 days	Primary	irPR and pCR††	Nivolumab	Yes	16 months
Cohort 3: single lesion injected a total of three times (first at baseline/day 0, second on day 21, and third on day 42)
10	IIIC	WT	Ipilimumab/nivolumab nd nivolumab	3	15 days	Secondary	NA	Nivolumab	No	13 months (died of disease
11	IV, M1a	WT	Nivolumab	2	~91 days	Primary	irPR	Nivolumab	Yes	13 months
12	IIIC	WT	Pembrolizumab	>5	25 days	Primary	irSD and pCR††	None	Yes	10 months

*Definitions of primary and secondary PD-1 resistance are based on Society for Immunotherapy of Cancer Immunotherapy Resistance Task Force recommendation and assigned per PI chart review.4
†irRC.16
‡Patient was taken off trial due to lack of clinical benefit as determined by the PI and started on additional therapy prior to 4-week confirmation of response.
§After PVSRIPO, patient 1 received four cycles ipilimumab and nivolumab followed by 7 months of maintenance nivolumab; after maintenance cycle 2 of nivolumab, biopsy of two cutaneous lesions showed no viable tumor. Patient 1 has persistent disease in the lymph node basin that was not biopsied but remains stable; all cutaneous/subcutaneous lesions also remain stable.
¶Patient deemed to have had inadequate exposure to determine the type of anti-PD-1 resistance, due to rapid disease progression.
**Confirmation of the irPR was done at 3 weeks instead of 4 weeks.
††Although some pigmented lesions remained, biopsy of injected and non-injected lesions showed no viable melanoma, consistent with pCR.
icPR, immune-related response criteria-confirmed partial response; IL, interleukin; irPR, immune-related response criteria-confirmed partial response; irRC, immune-related response criteria; NA, not assessable; pCR, pathological complete response; PD-1, programmed cell death protein 1; PI, principal investigator; T-VEC, talimogene laherparepvec; Tx, treatment; WT, Wild type.