In June 2021, the Company initiated Phase 2 of the clinical trial evaluating darovasertib and crizotinib combination in MUM based on observed early clinical activity of this combination. In the first cohort of the dose escalation portion of the Phase 1 clinical trial, an earlier-reported unconfirmed partial response of 54.3% tumor reduction has been subsequently confirmed with a 56.5% tumor reduction in a subsequent scan, which represents the deepest response observed to date in the Phase 1/2 clinical trial evaluating darovasertib as monotherapy or in combinations.
Drug-related adverse events observed in the darovasertib and crizotinib combination arm in MUM as of June 22, 2021 based on preliminary data from an unlocked database, primarily include: serious adverse events of syncope and hypotension, each of which resolved with patients continuing dosing; and adverse events that occurred in at least two treated patients of nausea, diarrhea, vomiting, edema, decreased appetite, rash, hypotension and syncope. The observed syncope and hypotension were transient, often occurring in the first week of dosing, and are being managed and mitigated through a one week run-in dosing regimen and by limiting use of certain concurrent medications such as diuretics.
In the darovasertib and binimetinib combination arm of the Phase 1 clinical trial, an earlier-reported unconfirmed partial response of 40.5% tumor reduction has been confirmed with a 51.7% tumor reduction in a subsequent scan, reflecting two confirmed partial responses out of nine evaluable MUM patients with at least two post-baseline scans (22%) per RECIST 1.1 guidelines.
Drug-related adverse events observed in the darovasertib and binimetinib combination arm in MUM, as of June 22, 2021 data cutoff based on preliminary data and analyses from an unlocked database, primarily include: serious adverse events of liver toxicity, nausea and vomiting, syncope and fall; and adverse events that occurred in greater than 10% of patients of nausea, vomiting, diarrhea, rash, edema, AST increase, ALT increase, fatigue, hypotension and creatine phosphokinase increase.
As of June 22, 2021, the Company has enrolled 30 MUM patients in the darovasertib and binimetinib combination arm, and 15 MUM patients in the darovasertib and crizotinib combination arm, and is continuing patient enrollment in each. The Company is targeting a further clinical data update for darovasertib combination(s) in the second half of 2021. The Company is planning to obtain FDA regulatory guidance on potential registration-enabling trial design for darovasertib monotherapy and/or darovasertib combination(s) in MUM in the first half of 2022.
Forward-Looking Statements
To the extent that statements contained herein are not descriptions of historical facts regarding the Company, they are forward-looking statements reflecting the current beliefs and expectations of management made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, including statements related to (i) the timing of additional clinical trial sites in the IDE397 Phase 1 dose escalation study, (ii) the obtention of pre-treatment and post-treatment tumor biopsies from patients enrolled into the IDE397 tumor biopsy cohort to evaluate PD response, (iii) exercise of the GSK option, cost sharing, milestone payments, profit share and royalties related to IDE397, and (iv) the timing of a clinical data update for either of the darovasertib combination arms and FDA guidance for potential darovasertib registrational pathway. Such forward-looking statements involve substantial risks and uncertainties that could cause the Company’s preclinical and clinical development programs, future results, performance, or achievements to differ significantly from those expressed or implied by the forward-looking statements. Such risks and uncertainties include, among others, the uncertainties inherent in the drug development process, including the Company’s programs’ early stage of development, the process of designing and conducting preclinical and clinical trials, the risk that results of earlier studies and trials may not be predictive of future trial results, the risk that regulatory authorities, including the FDA may not agree with the Company’s interpretation of the data from clinical trials of the Company’s drug candidates, the risk that the Company may experience delays in the commencement, enrollment, completion or analysis of clinical testing for its drug candidates, or significant issues regarding the adequacy of the Company’s clinical trial designs or the execution of its clinical trials may arise, which could result in increased costs and delays, or limit the Company’s ability to obtain regulatory approval, unexpected adverse side effects or inadequate therapeutic efficacy of the Company’s drug candidates that could delay or prevent clinical results, regulatory approval or commercialization, the timing of regulatory
