Darovasertib Neoadjuvant Monotherapy:
In the ongoing investigator-sponsored Phase 1 clinical trial (IST) captioned as “Neoadjuvant / Adjuvant trial of Darovasertib in Ocular Melanoma” (NADOM) being led by principal investigator Professor Anthony Joshua, MBBS, PhD, FRACP, Head Department of Medical Oncology, Kinghorn Cancer Centre, St. Vincent’s Hospital in Sydney with participating sites of Alfred Health and the Royal Victorian Eye and Ear Hospital in Melbourne, the study reports a preliminary interim update with an enrollment cut-off as of July 17, 2023 of seven patients treated to maximal response in the neo-adjuvant setting (up to 6 months of darovasertib monotherapy in patients who were enrolled with planned enucleation); 2 patients have confirmed Eye Saved (i.e., converted to plaque brachytherapy) with a third patient confirmed as plaque-eligible and is ongoing with darovasertib neo-adjuvant treatment until maximal benefit; providing 50% overall eye preservation rate for the evaluable patients. Of the evaluable patients (6 of 7) treated to maximal benefit, defined as at least one ultrasound scan, approximately 83% of patients had tumor shrinkage. Two patients did not complete their treatment to maximal response; one patient had sub-retinal blood present at baseline and with lack of shrinkage and visual deterioration, the patient discontinued treatment after 6 weeks. A non-evaluable second patient had a Grade 3 drug-related AE of dermatitis and discontinued treatment before first scan. Two out of four additional patients after the enrollment cutoff date of July 17, 2023 are likely plaque eligible and are continuing darovasertib neoadjuvant therapy until maximal benefit with 1 patient being enucleated. In total, 11 patients eligible to receive 6 months of neoadjuvant therapy are enrolled to date in the neoadjuvant UM enucleation cohort IST.
The Company’s Phase 2 company sponsored (neo)adjuvant darovasertib monotherapy study is observing rapid enrollment to date, with 6 UM patients now enrolled, including 4 enucleation patients and 2 plaque-therapy patients.
Synthetic Lethality Pipeline:
For IDE397, a potential first-in-class MAT2A inhibitor, we have observed multiple PRs in the Phase 2 expansion evaluating priority solid tumor types of squamous NSCLC and bladder cancer. There have been 8 patients dosed in the Phase 2 expansion in the priority tumor types, of which 2 have not yet had a first tumor scan assessment. The PRs include an earlier reported -33% tumor shrinkage by CT-PET (without contrast) for a squamous NSCLC patient, and a confirmed PR (47% tumor shrinkage) by RECIST 1.1 with IDE397 in a previously undisclosed tumor type (bladder cancer). This bladder cancer patient has converted to a complete response by RECIST 1.1 at the week 18 CT-scan. In addition, of patients evaluable for ctDNA pre and post treatment, a high ctDNA molecular response rate of 83% was observed in these MTAP-deletion priority tumor types. As of the October 13, 2023 cut-off date, in the dose escalation and expansion phases, we have observed relatively low rates of drug-related discontinuations and SAEs. The IDE397 and AMG 193 clinical combination study in MTAP-deletion solid tumors is in ongoing dose escalation, with an expansion focus on NSCLC.
For IDE161, a potential first-in-class PARG inhibitor, we have observed multiple PRs by RECIST 1.1. and tumor shrinkage in priority solid tumor types early in the Phase 1 dose escalation and at the expansion dose. There have been a total of 7 patients treated at the expansion dose as of the October 13 2023 cut-off date, of which 2 patients have not yet had a first scan tumor assessment. The earlier reported IDE161 partial response at first scan in a BRCA1/2 endometrial cancer patient, is now a confirmed PR by RECIST 1.1 at the second scan. At the IDE161 expansion dose, we have observed no drug-related discontinuations or SAEs as of the October 13, 2023 cut-off date.