Targovax announces encouraging results from part 1 of the ONCOS-102 and Keytruda combination trial in anti-PD1 refractory melanoma

• One complete response (CR) and two partial responses (PR) observed for the nine patients in part 1 (33% ORR), who received only three ONCOS-102 injections
• Innate and adaptive immune activation observed in nine out of nine patients

Oslo, Norway, 8 July, 2019 - Targovax ASA (OSE: TRVX), a clinical stage biotechnology company developing oncolytic viruses to target hard-to-treat solid tumors, today announces that clinical responses were observed in 3 out of 9 patients in part 1 of the ONCOS-102 and Keytruda combination trial in anti-PD1 checkpoint inhibitor (CPI) refractory advanced melanoma, corresponding to an overall response rate (ORR) of 33%. 

In this trial, ONCOS-102 immune activation is being tested in patients with advanced, unresectable melanoma who have had disease progression on treatment with anti-PD1 CPI. This is a particularly challenging patient population, with few treatment alternatives available. The nine patients in part 1 of the trial were given three intra-tumoral ONCOS-102 injections during the first week, followed by re-challenge with the anti-PD1 CPI Keytruda. The primary and secondary endpoints of the trial are to assess safety, immune activation and clinical responses of ONCOS-102 and Keytruda combination treatment. The main scientific aim is to test the hypothesis that ONCOS-102 can immune activate anti-PD1 resistant patients to respond to re-challenge with an anti-PD1 CPI.

Part 1 safety data shows that the sequential ONCOS-102 and Keytruda treatment regimen is well tolerated. The efficacy is also very encouraging, with three of nine patients demonstrating a clinical response (33% ORR); one patient had a complete response (CR) and two patients had partial responses (PR) according to RECIST1.1 and irRECIST assessment criteria. Although the patient number is small, these results compare favorably to reports from other explorative immunotherapy trials in this hard-to-treat population. Importantly, the data also confirms the hypothesis that ONCOS-102 is able to immune activate treatment resistant tumors to respond to re-challenge with an anti-PD-1 CPI.

ONCOS-102 was also seen to induce profound innate and adaptive immune activation. By week three, prior to starting Keytruda treatment, systemic increases in pro-inflammatory cytokines were observed in all nine patients (IL-6, TNFα and/or IFNγ), demonstrating potent systemic immune activation in response to the intra-tumoral ONCOS-102 injections. At the tumor level, increased infiltration of CD8+ T-cells were found in eight out of nine patients and the relative level of activated CD8+ T-cells (GrzB+) increased in all nine patients. Examples of increased T-cell infiltration into lesions not injected with ONCOS-102 were also observed. In addition, T-cells recognizing specific tumor antigens were found in circulation in four patients (MAGE-A1 and/or NY-ESO-1). These data suggest that the initial innate immune activation is translated into systemic anti-tumor immune responses.

Part 2 of the trial is currently enrolling patients, where safety and efficacy of a more intensive treatment regimen of twelve ONCOS-102 injections will be evaluated. The trial is running at Memorial Sloan Kettering Cancer Centre in New York, Fox Chase Cancer Centre, Philadelphia, and the University of Maryland, Baltimore.

Dr. Alexander Shoushtari, Principal Investigator, Memorial Sloan Kettering Cancer Centre, New York said: “It is encouraging to see clinical responses in this hard-to-treat population of advanced melanoma. Earlier this year, we decided to expand the trial to test a more intensified schedule of ONCOS-102, and it will be interesting to see whether this regimen can generate more and deeper clinical responses.”

Dr. Magnus Jäderberg, CMO of Targovax, said: “We are very pleased to confirm our hypothesis that ONCOS-102 has the potential to immune activate checkpoint inhibitor resistant patients to respond to PD-1 blockade with Keytruda. It is promising to see this level of clinical responses after only three ONCOS-102 injections, including a complete response, which is rare in this heavily pre-treated patient population. Based on our experience so far, we speculate that patients will benefit from receiving more ONCOS-102 injections over a longer period of time and we will follow with interest the effect of the intensified dosing regimen in the second patient cohort of the trial.”

For further information, please contact:
Renate Birkeli, Investor Relations
Phone: +47 922 61 624
Email: renate.birkeli@targovax.com

Media and IR enquires:
Andreas Tinglum - Corporate Communications (Norway)
Phone: +47 9300 1773
Email: andreas.tinglum@corpcom.no

About Targovax

Activating the patient's immune system to fight cancer

Targovax (OSE:TRVX) is a clinical stage biotechnology company developing immune activators to target hard to treat solid tumors. Immuno-oncology is currently one of the fastest growing therapeutic fields in medicine.

Targovax’s lead product candidate, ONCOS-102, is a genetically modified oncolytic adenovirus, which has been engineered to selectively infect and replicate in cancer cells. It is used as a therapeutic cancer vaccine and has been shown to activate the immune system to generate tumor-specific immune responses. In phase I trials, ONCOS-102 induced both local and systemic innate and adaptive immune activation, which has been associated with clinical benefit. ONCOS-102’s lead indication is mesothelioma, where the virus is currently being tested in a randomized phase I/II trial expected to report around end 2019 – early 2020.