– Combination of Rebastinib and Paclitaxel Exhibited Encouraging Preliminary Anti-tumor Activity Across Treatment Arms in the Ongoing Phase 1b/2 Clinical Study –
– DCC-3116 Represents a Differentiated Approach to Autophagy Inhibition and a First-in-Class Opportunity for a New Therapeutic Modality in Mutant RAS Cancers –
WALTHAM, MA, USA I October 28, 2019 I Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, today presented data from its ongoing Phase 1b/2 clinical study of rebastinib, an oral TIE2 kinase inhibitor, in combination with paclitaxel at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. In addition, the Company also presented data from preclinical studies of DCC-3116, a potential first-in-class autophagy inhibitor to treat mutant RAS cancers.
“Both of these datasets highlight the broad applicability of Deciphera’s kinase switch control platform and our potential to address unmet needs in oncology,” said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. “We look forward to continuing Part 2 of our Phase 1b/2 study of rebastinib in combination with paclitaxel with the insights garnered from Part 1 of the study. We also look forward to advancing the IND-enabling studies for DCC-3116.”
Rebastinib
The Phase 1b/2 study of rebastinib in combination with paclitaxel is a two-part, open-label, multicenter study assessing the safety, tolerability, anti-tumor activity and pharmacokinetics of multiple doses of rebastinib in patients with advanced or metastatic solid tumors. Data presented today are from 43 patients from Part 1 of the study, including 24 patients from the rebastinib 50 mg oral twice a day (BID) with paclitaxel 80 mg/m2 IV cohort and 19 patients from the rebastinib 100 mg oral BID with paclitaxel 80 mg/m2 IV cohort. Preliminary results from Part 1 included:
- Encouraging preliminary anti-tumor activity was observed in both dose cohorts, with objective responses seen across a heavily pre-treated patient population, including patients with prior exposure to paclitaxel. Objective responses were seen in eight patients including ovarian (3), breast (2), carcinosarcoma (2), and peritoneal mesothelioma (1), seven of whom had prior therapy with paclitaxel or docetaxel. A best response of partial response (PR) was observed in 5 of 24 patients in the 50 mg BID dose cohort and 3 of 19 patients in the 100 mg BID dose.
- Exposure to rebastinib was dose-proportional at the 50 mg BID and 100 mg BID doses when given in combination with paclitaxel.
- Mean circulating Ang-2 levels increased with exposure to higher doses of rebastinib in combination with paclitaxel, indicating TIE2 inhibition.
- Rebastinib in combination with paclitaxel was generally well-tolerated, with similar frequency of treatment-emergent adverse events (TEAEs) between the two dose cohorts, and most TEAEs were consistent with first-in-human studies of rebastinib or known to be associated with treatment with paclitaxel.
- Based on the observed frequency of muscular weakness in preliminary data from the ongoing Part 2 portion of the study with the 100 mg BID dose, the recommended phase 2 dose (RP2D) was changed to 50 mg BID.
DCC-3116
DCC-3116 is designed as a potential autophagy inhibitor by selectively targeting ULK kinase. Autophagy is a cellular pathway that has been shown to be upregulated in mutant RAS cancers and that also mediates resistance to inhibitors of the RAS signaling pathway. Subject to favorable investigational new drug (IND)-enabling studies and filing and activation of an IND application, Deciphera intends to develop DCC-3116 for the potential treatment of mutant RAS cancers in combination with inhibitors of downstream effector targets including RAF, MEK, or ERK inhibitors (MAPK inhibitors) as well as with direct inhibitors of mutant RAS. Preclinical data presented today included the following:
- DCC-3116 was shown to be a potent, selective, and tight-binding inhibitor of ULK kinase.
- DCC-3116 inhibited phosphorylation of the ULK substrate ATG13 in cancer cells and exhibited synergy in vitro in combination with MAPK inhibitors in inhibiting cancer cell growth.
- Oral doses of DCC-3116 led to sustained inhibition of ULK activity as shown by the inhibited phosphorylation of the ULK substrate ATG13 in vivo.
- DCC-3116 exhibited synergy with MAPK inhibitors in tumor growth inhibition in mouse models.
A copy of each poster presentation is available at www.deciphera.com.
About Rebastinib
Rebastinib is an investigational, orally administered, potent and selective inhibitor of the TIE2 kinase, the receptor for angiopoietins, an important family of vascular growth factors in the tumor microenvironment that also activate pro-tumoral TIE2 expressing macrophages. In a Phase 1 clinical study, biomarker data have demonstrated rebastinib-induced increases in the TIE2 ligand angiopoietin 2, providing evidence of TIE2 inhibition. Rebastinib is currently being evaluated in a Phase 1b/2 clinical study in combination with paclitaxel (NCT03601897) and in a Phase 1b/2 clinical study in combination with carboplatin (NCT03717415).
About DCC-3116
DCC-3116 is a potential first-in-class small molecule designed to inhibit cancer autophagy, a key tumor survival mechanism, by inhibiting the ULK kinase. Subject to favorable investigational new drug (IND)-enabling studies and filing and activation of an IND application, expected in mid-2020, Deciphera intends to develop DCC-3116 for the potential treatment of mutant RAS cancers in combination with inhibitors of downstream RAS effector targets including RAF, MEK, or ERK inhibitors as well as with direct inhibitors of mutant RAS.
About Deciphera Pharmaceuticals
Deciphera Pharmaceuticals is a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients by addressing key mechanisms of drug resistance that limit the rate and/or durability of response to existing cancer therapies. Our small molecule drug candidates are directed against an important family of enzymes called kinases, known to be directly involved in the growth and spread of many cancers. We use our deep understanding of kinase biology together with a proprietary chemistry library to purposefully design compounds that maintain kinases in a “switched off” or inactivated conformation. These investigational therapies comprise tumor-targeted agents designed to address therapeutic resistance causing mutations, immuno-targeted agents designed to control the activation of immunokinases that suppress critical immune system regulators, and agents designed to inhibit reprogramming of cancer cell metabolism. We have used our platform to develop a diverse pipeline of tumor-targeted, immuno-targeted, and metabolism-targeted drug candidates designed to improve outcomes for patients with cancer by improving the quality, rate and/or durability of their responses to treatment.
SOURCE: Deciphera Pharmaceuticals
Post Views: 25
– Combination of Rebastinib and Paclitaxel Exhibited Encouraging Preliminary Anti-tumor Activity Across Treatment Arms in the Ongoing Phase 1b/2 Clinical Study –
– DCC-3116 Represents a Differentiated Approach to Autophagy Inhibition and a First-in-Class Opportunity for a New Therapeutic Modality in Mutant RAS Cancers –
WALTHAM, MA, USA I October 28, 2019 I Deciphera Pharmaceuticals, Inc. (Nasdaq:DCPH), a clinical-stage biopharmaceutical company addressing key mechanisms of tumor drug resistance, today presented data from its ongoing Phase 1b/2 clinical study of rebastinib, an oral TIE2 kinase inhibitor, in combination with paclitaxel at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics in Boston. In addition, the Company also presented data from preclinical studies of DCC-3116, a potential first-in-class autophagy inhibitor to treat mutant RAS cancers.
“Both of these datasets highlight the broad applicability of Deciphera’s kinase switch control platform and our potential to address unmet needs in oncology,” said Matthew L. Sherman, M.D., Executive Vice President and Chief Medical Officer of Deciphera. “We look forward to continuing Part 2 of our Phase 1b/2 study of rebastinib in combination with paclitaxel with the insights garnered from Part 1 of the study. We also look forward to advancing the IND-enabling studies for DCC-3116.”
Rebastinib
The Phase 1b/2 study of rebastinib in combination with paclitaxel is a two-part, open-label, multicenter study assessing the safety, tolerability, anti-tumor activity and pharmacokinetics of multiple doses of rebastinib in patients with advanced or metastatic solid tumors. Data presented today are from 43 patients from Part 1 of the study, including 24 patients from the rebastinib 50 mg oral twice a day (BID) with paclitaxel 80 mg/m2 IV cohort and 19 patients from the rebastinib 100 mg oral BID with paclitaxel 80 mg/m2 IV cohort. Preliminary results from Part 1 included:
- Encouraging preliminary anti-tumor activity was observed in both dose cohorts, with objective responses seen across a heavily pre-treated patient population, including patients with prior exposure to paclitaxel. Objective responses were seen in eight patients including ovarian (3), breast (2), carcinosarcoma (2), and peritoneal mesothelioma (1), seven of whom had prior therapy with paclitaxel or docetaxel. A best response of partial response (PR) was observed in 5 of 24 patients in the 50 mg BID dose cohort and 3 of 19 patients in the 100 mg BID dose.
- Exposure to rebastinib was dose-proportional at the 50 mg BID and 100 mg BID doses when given in combination with paclitaxel.
- Mean circulating Ang-2 levels increased with exposure to higher doses of rebastinib in combination with paclitaxel, indicating TIE2 inhibition.
- Rebastinib in combination with paclitaxel was generally well-tolerated, with similar frequency of treatment-emergent adverse events (TEAEs) between the two dose cohorts, and most TEAEs were consistent with first-in-human studies of rebastinib or known to be associated with treatment with paclitaxel.
- Based on the observed frequency of muscular weakness in preliminary data from the ongoing Part 2 portion of the study with the 100 mg BID dose, the recommended phase 2 dose (RP2D) was changed to 50 mg BID.
DCC-3116
DCC-3116 is designed as a potential autophagy inhibitor by selectively targeting ULK kinase. Autophagy is a cellular pathway that has been shown to be upregulated in mutant RAS cancers and that also mediates resistance to inhibitors of the RAS signaling pathway. Subject to favorable investigational new drug (IND)-enabling studies and filing and activation of an IND application, Deciphera intends to develop DCC-3116 for the potential treatment of mutant RAS cancers in combination with inhibitors of downstream effector targets including RAF, MEK, or ERK inhibitors (MAPK inhibitors) as well as with direct inhibitors of mutant RAS. Preclinical data presented today included the following:
- DCC-3116 was shown to be a potent, selective, and tight-binding inhibitor of ULK kinase.
- DCC-3116 inhibited phosphorylation of the ULK substrate ATG13 in cancer cells and exhibited synergy in vitro in combination with MAPK inhibitors in inhibiting cancer cell growth.
- Oral doses of DCC-3116 led to sustained inhibition of ULK activity as shown by the inhibited phosphorylation of the ULK substrate ATG13 in vivo.
- DCC-3116 exhibited synergy with MAPK inhibitors in tumor growth inhibition in mouse models.
A copy of each poster presentation is available at www.deciphera.com.
About Rebastinib
Rebastinib is an investigational, orally administered, potent and selective inhibitor of the TIE2 kinase, the receptor for angiopoietins, an important family of vascular growth factors in the tumor microenvironment that also activate pro-tumoral TIE2 expressing macrophages. In a Phase 1 clinical study, biomarker data have demonstrated rebastinib-induced increases in the TIE2 ligand angiopoietin 2, providing evidence of TIE2 inhibition. Rebastinib is currently being evaluated in a Phase 1b/2 clinical study in combination with paclitaxel (NCT03601897) and in a Phase 1b/2 clinical study in combination with carboplatin (NCT03717415).
About DCC-3116
DCC-3116 is a potential first-in-class small molecule designed to inhibit cancer autophagy, a key tumor survival mechanism, by inhibiting the ULK kinase. Subject to favorable investigational new drug (IND)-enabling studies and filing and activation of an IND application, expected in mid-2020, Deciphera intends to develop DCC-3116 for the potential treatment of mutant RAS cancers in combination with inhibitors of downstream RAS effector targets including RAF, MEK, or ERK inhibitors as well as with direct inhibitors of mutant RAS.
About Deciphera Pharmaceuticals
Deciphera Pharmaceuticals is a clinical-stage biopharmaceutical company focused on improving the lives of cancer patients by addressing key mechanisms of drug resistance that limit the rate and/or durability of response to existing cancer therapies. Our small molecule drug candidates are directed against an important family of enzymes called kinases, known to be directly involved in the growth and spread of many cancers. We use our deep understanding of kinase biology together with a proprietary chemistry library to purposefully design compounds that maintain kinases in a “switched off” or inactivated conformation. These investigational therapies comprise tumor-targeted agents designed to address therapeutic resistance causing mutations, immuno-targeted agents designed to control the activation of immunokinases that suppress critical immune system regulators, and agents designed to inhibit reprogramming of cancer cell metabolism. We have used our platform to develop a diverse pipeline of tumor-targeted, immuno-targeted, and metabolism-targeted drug candidates designed to improve outcomes for patients with cancer by improving the quality, rate and/or durability of their responses to treatment.
SOURCE: Deciphera Pharmaceuticals
Post Views: 25
