Benzinga | Oct 7, 2021 09:19AM EDT

Deciphera Presents Preclinical Data From DCC-3116 Program At AACR-NCI-EORTC International Conference

Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a commercial-stage biopharmaceutical company developing innovative medicines to improve the lives of people with cancer, today announced the presentation of preclinical data from the Company's first-in-class selective ULK kinase inhibitor, DCC-3116, in combination with EGFR inhibitors in non-small cell lung cancer (NSCLC) models at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics.

"The data presented today show that DCC-3116 inhibits the autophagy that develops as a resistance mechanism after treatment with EGFR inhibitors in multiple EGFR-mutant NSCLC cell lines and that DCC-3116 decreases tumor burden when combined with EGFR inhibitors. These findings are particularly important as EGFR is mutated in approximately 30% of NSCLC patients, the vast majority of whom develop resistance to EGFR inhibitors," said Matthew L. Sherman, M.D., Chief Medical Officer of Deciphera. "These results reinforce the broad potential of autophagy inhibition as a mechanism to address the challenge of drug resistance in the treatment of cancer."

Results from the study, presented in a poster titled "DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with EGFR inhibitors osimertinib and afatinib in NSCLC preclinical models" are summarized below. The poster presentation is available on-demand via the meeting website and on the Company's website at www.deciphera.com/presentations-publications.

In Vitro Data Show Ability of DCC-3116 to Reduce Autophagy that Develops as a Resistance Mechanism after Treatment with EGFR Inhibitors in NSCLC Cell Lines

-- EGFR inhibitors gefitinib, erlotinib and osimertinib, and the ErbB-family inhibitor, afatinib, activated autophagy three to four-fold over basal levels as measured by pATG13, a cellular substrate of autophagy-initiating kinases ULK1/2, in the EGFR exon 19-deleted HCC827 NSCLC cell line. DCC-3116, a potent inhibitor of ULK1 and ULK2, was shown to inhibit both basal and EGFR-induced phosphorylation of pATG13.

-- Treatment of the EGFR T790M-mutated NSCLC cell line H1975 with osimertinib or afatinib, which inhibit the T790M mutation, induced autophagy three-fold over basal levels while treatment with gefitinib or erlotinib, which are not able to inhibit the T790M mutation, did not induce ULK-mediated ATG13 phosphorylation. DCC-3116 potently inhibited osimertinib and afatinib-induced phosphorylation of ATG13 and inhibited the increase in autophagosomes induced by these agents.

In Vivo Data Show that Combination of DCC-3116 with EGFR Inhibitors Resulted in Significantly Greater Tumor Responses in NSCLC Xenograft Model

-- The combination of DCC-3116 with osimertinib or afatinib resulted in significantly greater tumor responses than single agent treatments in the H1975 EGFR-mutant xenograft model.

The clinical development plan for DCC-3116 will initially focus on documented RAS and RAF cancer mutations, which utilize autophagy for tumor growth and survival. DCC-3116 is currently being investigated in a Phase 1, multicenter, open-label, first-in-human study designed to evaluate the safety, tolerability, clinical activity, pharmacokinetics, and pharmacodynamics of DCC-3116 as a single agent and in combination with trametinib, a commercially available MEK inhibitor, in patients with advanced or metastatic tumors with a mutant RAS or RAF gene. Following the dose escalation phase, combination expansion cohorts are currently planned in patients with advanced or metastatic pancreatic ductal adenocarcinoma with KRAS or BRAF mutations, non-small cell lung cancer (NSCLC) with KRAS, NRAS, or BRAF mutations, colorectal cancer with KRAS, NRAS, or BRAF mutations, and melanoma with NRAS or BRAF mutations. Combination expansion cohorts are planned to evaluate DCC-3116 in combination with trametinib. Initial data from the Phase 1 dose escalation cohorts is expected in 2022.