Background: PD-1 blockade showed promising efficacy in facilitating tumor shrinkage for broad type of cancer patients, but objective response rates are very limited. The antitumor potential of oncolytic adenoviruses has been demonstrated in preclinical and clinical studies. In addition to the specific killing of cancer cells via oncolytic virus, these agents prompt the immune system to stimulate an antitumor immune response. OBP-301 is an oncolytic adenovirus in which gene is modified to be able to selectively replicate in cancer cells by introducing human telomerase reverse transcriptase (hTERT) promotor. Further antitumor effect will be expected activating of two different antitumor immunity by using OBP-301 in combination with pembrolizumab. Therefore, we initiated phase I study to evaluate the safety and efficacy of OBP-301 with pembrolizumab. Methods: The major eligibility criteria is patients with advanced or metastatic solid tumor not responded to or intolerant of standard chemotherapies, and with possibility of intratumoral injection. History of anti PD-1/PD-L1/PD-L2 antibody treatment is acceptable. Phase Ia part was designed to determine the recommended dose in a “3+3” cohort-based dose escalation design of OBP-301 (1x10¹⁰VP on cohort 1, 1x10¹¹VP on cohort 2 and 1x10¹²VP on cohort 3) with pembrolizumab (200mg/body q3w). OBP-301 is administered at day1, day15, and, Day29 by intratumoral injection and pembrolizumab is administered at day 8 and thereafter every 3 weeks. Primary endpoint is dose limiting toxicity. Secondary endpoint is response rate, progression free survival, and rate of adverse event. Phase Ib part was designated to evaluate the safety and efficacy of the recommended dose OBP-301 selected in phase Ia part in combination with pembrolizumab in 10 patients. We will also investigate biomarker study using paired samples of both tumor biopsy and blood. The patient enrollment has been started in October 2017. Clinical trial information: NCT03172819