Table 2.

Overview of Pexa-Vec clinical trials

Indication	Phase	Treatment regimen	Patients enrolled	Key findings
HCC program	Phase 1 liver tumor	Intratumoral dose escalation 1×108 pfu to 3×109 pfu	14	– MTD identified (1×109 pfu) – Pexa-Vec replication and transgene expression confirmed – Antitumor activity observed at all dose levels18
	Phase II randomized primary liver cancer (HCC)	Intratumoral dose finding 1×108 pfu vs 1×109 pfu	30	– Pexa-Vec tolerable at both dose levels in HCC patients – Improved survival at high-dose vs low-dose control (median 14.1 months vs 6.7 months; hazard ratio 0.39; P-value =0.02)26
	Phase IIb second line HCC (sorafenib refractory)	IV + intratumoral Pexa-Vec (1×109 pfu) plus BSC versus BSC	129 (86 arm A)	– Pexa-Vec plus BSC did not prolong overall survival when compared to BSC alone in advanced, poor-prognosis patient population
RCC program	Phase II	Multiple IV infusions 1×109 pfu	17	– Study ongoing
CRC program	Phase 1, Phase II studies	Multiple IV infusions alone or in combination with irinotecan	60+ patients	– Studies ongoing
Proof-of-concept studies	Phase 1 IV dose escalation	Single IV Pexa-Vec infusion (1×105 pfu/kg to 3×107 pfu/kg)	23	– IV Pexa-Vec well-tolerated (MFD defined) – Dose-dependent intravenous delivery to metastatic tumors demonstrated (biopsy-proven) – Evidence of antitumor activity at high dose17
	Phase 1 intratumoral dose escalation	Multiple IT Pexa-Vec injections in melanoma patients	7	– First-in-man study of Pexa-Vec – Pexa-Vec well-tolerated, MFD defined – Inflammation demonstrated in injected tumors – Evidence of antitumor activity23
	Phase 1 mechanism of action study	Multiple IT Pexa-Vec injections in melanoma patients	10	– Pexa-Vec replication confirmed after injection of superficial tumors24

Abbreviations: BSC, best supportive care; CRC, colorectal cancer; HCC, hepatocellular carcinoma; IV, intravenous; IT, intratumoral; MFD, maximum feasible dose; MTD, maximum tolerated dose; RCC, renal cell carcinoma; pfu, plaque-forming unit.