dm+d

Unassigned

New Medicines

Solid tumours

Information

New molecular entity
Replimune
Replimune

Development and Regulatory status

Phase I Clinical Trials
None
None
Mar 22Replimune note that strong initial data with RP2 monotherapy and in combination with nivolumab supports the advancement of RP2 into new and difficult to treat tumor types. It will announce a broad RP2 Phase 2 development plan including new clinical trials in advanced/metastatic squamous cell carcinoma of the head and neck (SCCHN), hepatocellular carcinoma (HCC), and colorectal cancer (CRC) [2].

Category

A next generation oncolytic immunotherapy which expresses a genetically encoded anti-CTLA-4 antibody in addition to expressing GALV-GP-R- and GM-CSF. It is based on the Immulytic™ platform that utilises the ability of viruses to selectively replicate in and destroy tumour tissue, and generate an autologous immune response to the patients particular complement of tumour antigens.
Variable depending on tumour type.
Solid tumours
Intratumoural

Trial or other data

Apr 22PI (NCT04336241) trial is due to complete collection of primary outcome data in Jul 23 [1].
Nov 20Interim data from the PI (NCT04336241) trial showed that, in the nine-patient monotherapy cohort with RP2, two of the initial three patients who achieved response remained in response, these being a patient with esophageal cancer (partial response; previously anti-PDL1 failed) at 22 months from entering the trial and a patient with mucoepidermoid carcinoma (complete response) at 19 months from entering the trial. As previously reported, the third responding patient with uveal melanoma with a partial response (Yervoy/Opdivo failed) progressed at 15 months from entering the trial. Updated data from the 30-patient cohort of RP2 in combination with Opdivo (nivolumab) showed durable responses ongoing at out to >425 days. Until now, seven of the 30 patient (23.3%) cohort of RP2 in combination with nivolumab have achieved partial responses, with additional patients still on study with the opportunity to achieve a response. Six of the seven responses are ongoing with depth of response having been maintained or deepened over time. The responding patients are four of nine patients with cutaneous melanoma (all anti-PD1 or anti-PD1 and anti-CTLA-4 failed), two of eight patients with uveal melanoma (anti-PD1 or anti-PD1 and anti-CTLA-4 failed) and one of three patients with squamous cell carcinoma of the head and neck (anti-PD1 failed [7] . Results from phase I trial evaluating RP 2 in heavily pre-treated patients demonstrated compelling monotherapy clinical activity in patients with immune insensitive tumor types. Nine patients were treated with single agent RP 2 and one patient (with mucoepidermoid carcinoma) had an ongoing complete response and two other patients (with uveal melanoma and esophageal cancer) had ongoing partial responses. All three of these responses were durable [3].
Oct 19PI trial to assess the safety, tolerability and to determine the optimal dose of RP2 alone and in combination with anti-PD1 therapy (nivolumab) in patients with solid tumours starts (NCT04336241; RP2-001-18). This is an open-label, dose escalation study of RP2 in 36 adults to determine the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D), as well as to evaluate preliminary efficacy. It will recruit in the UK at The Clatterbridge Cancer Centre, Churchill Hospital in Oxford, and the Royal Marsden Hospital [1].