inlexisertib (DCC-3116) / Ono Pharma - LARVOL DELTA

A Phase 1/2 Study of Inlexisertib (DCC-3116) in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov) - P1/2 | N=144 | Active, not recruiting | Sponsor: Deciphera Pharmaceuticals, LLC | Recruiting ➔ Active, not recruiting

Enrollment closed • First-in-human • Monotherapy • Colorectal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRAF • KRAS • NF1 • NRAS

DCC-3116 IN COMBINATION WITH RIPRETINIB FOR PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR: A PHASE 1/2 STUDY (CTOS 2024) - P1/2 | "In the INTRIGUE trial, ripretinib demonstrated comparable efficacy and more favorable safety compared with sunitinib in second-line advanced GIST...In part 2, second-line patients with confirmed GIST with a KIT exon 11 mutation who experienced disease progression on or intolerance to first-line imatinib will be enrolled... N/A Trials in progress"

Clinical • Combination therapy • Metastases • P1/2 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • PDGFRA

A Study of DCC-3116 in Combination with Anticancer Therapies in Participants with Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 ➔ Mar 2029

Trial completion date • Gastrointestinal Cancer • Oncology • Sarcoma • BRAF • KIT • PDGFRA

A patent review of UNC-51-like kinase 1/2 inhibitors (2019-present). (PubMed, Expert Opin Ther Pat) - "Despite the great success of ULK1/2 inhibitors development, ULK1/2 inhibitors are ATP competitive inhibitors of aminopyrimidines currently, and most ULK1/2 inhibitors are still in the preclinical research stage, with only DCC-3116 entered clinical research. Therefore, developing highly selective ULK1/2 inhibitors with low side effects and high bioavailability remains a challenging and promising research direction."

Journal • Review • Oncology

DCC-3116 In Combination with Sotorasib in Advanced or Metastatic KRASG12C-Mutant Cancers: First-in-human Phase 1/2 Study (IASLC-WCLC 2024) - P1/2 | "Secondary endpoints for both parts include progression-free survival, duration of response, and pharmacokinetics; exploratory endpoints include pharmacodynamics. Part 1 of this study is currently enrolling patients."

Combination therapy • Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancer. (PubMed, Elife) - "Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC)...Moreover, the combination of DCC-3116, a selective ULK1/2 inhibitor, plus sotorasib displays cooperative/synergistic suppression of human KRASG12C-driven lung cancer cell proliferation in vitro and superior tumor control in vivo. Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer."

Journal • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

DCC-3116 in combination with ripretinib for patients with advanced gastrointestinal stromal tumor: A phase 1/2 study. (ASCO 2024) - P1/2 | "In the INTRIGUE trial, ripretinib demonstrated comparable efficacy and more favorable safety compared with sunitinib in second-line advanced GIST...In part 2, second-line pts with confirmed GIST with a KIT exon 11 mutation and disease progression on or intolerance to first-line imatinib will be enrolled...The primary objective of part 2 is to determine the objective response rate per modified Response Evaluation Criteria in Solid Tumors version 1.1. The study is currently enrolling."

Clinical • Combination therapy • Metastases • P1/2 data • Stroma • Gastrointestinal Cancer • Gastrointestinal Disorder • Gastrointestinal Stromal Tumor • Infectious Disease • Oncology • Sarcoma • PDGFRA

Ono Announces Results of Tender Offer to Acquire Deciphera Pharmaceuticals and Completion of Acquisition of Deciphera (a Wholly Owned Subsidiary of Ono) (PRNewswire) - "Ono Pharmaceutical...today announced that it has successfully completed the tender offer, previously announced on April 30, 2024 to acquire all outstanding shares of common stock of a US biopharmaceutical company, Deciphera Pharmaceuticals, Inc...for US$25.60 per share (total amount of approximately US$2.4 billion) net to the seller in cash, without interest thereon and less any applicable withholding taxes, through its wholly owned subsidiary, Topaz Merger Sub, Inc...established in the State of Delaware, United States, solely for the purpose of engaging in the transactions contemplated in the Merger Agreement....'Through this acquisition, we will leverage Deciphera's excellent research and development capabilities in the oncology field and its sales power in Europe and the United States, and work to further accelerate the expansion of our pipeline and global expansion, which are part of our growth strategies.'"

M&A • Gastrointestinal Stromal Tumor • Graft versus Host Disease • Hematological Malignancies • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor • Tenosynovial Giant Cell Tumor

A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov) - P1/2 | N=173 | Recruiting | Sponsor: Deciphera Pharmaceuticals LLC | N=323 ➔ 173 | Trial completion date: Oct 2024 ➔ Aug 2028 | Trial primary completion date: Apr 2024 ➔ Aug 2027

Combination therapy • Enrollment change • Metastases • Monotherapy • Trial completion date • Trial primary completion date • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Ductal Adenocarcinoma • Solid Tumor • BRAF • KRAS • NF1 • NRAS

Deciphera Pharmaceuticals Announces Oral Presentation of Results from MOTION Pivotal Phase 3 Study of Vimseltinib in Patients with Tenosynovial Giant Cell Tumor (TGCT) at the 2024 ASCO Annual Meeting and Online Publication in The Lancet (Businesswire) - "This is a phase 1/2, multicenter study designed to evaluate the safety, tolerability, and efficacy of DCC-3116 in combination with ripretinib. In Part 1, eligible patients will receive escalating oral doses of DCC-3116 combined with ripretinib 150 mg once daily (QD); the safety will be evaluated and the recommended phase 2 dose (RP2D) will be determined. In Part 2, eligible patients will receive the RP2D of DCC-3116 in combination with ripretinib 150 mg QD; antitumor activity will be evaluated. The trial is currently enrolling in the phase 1 dose escalation portion."

Trial status • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=94 | Recruiting | Sponsor: Deciphera Pharmaceuticals LLC | N=170 ➔ 94

Combination therapy • Enrollment change • Metastases • Gastrointestinal Cancer • Oncology • Sarcoma • BRAF • KIT • PDGFRA

Inhibition of ULK and KRASG12C control tumor growth in preclinical models of lung cancer (AACR 2024) - "Consequently, we have generated genetically engineered mouse models (GEMMs) of KRASG12C-driven lung cancer in which LKB1 is silenced to further investigate the role of LKB1 in the autophagy response of KRASG12C-driven lung cancers to pathway-targeted blockade of oncogenic KRAS signaling. We have treated KRASG12C-driven GEMMs with sotorasib and/or DCC-3116 to test the sensitivity of lung tumors to these treatment options."

Preclinical • Lung Cancer • Oncology • Solid Tumor • KRAS • STK11

Discovery of DCC-3116. A selective, first-in-class ULK inhibitor for cancer therapy (ACS-Sp 2024) - "We disclose herein the development of DCC-3116, a potent and selective inhibitor of ULK1/2 and report on its promising preclinical activity in a series of in vitro and in vivo studies. DCC-3116 is currently in Phase 1 clinical development in combination with RTK pathway inhibitors in patients with advanced or metastatic solid tumors with mutations in the pathway."

Oncology • Solid Tumor

Deciphera Pharmaceuticals Announces Planned 2024 Corporate Milestones Supporting Evolution to a Self-Sustaining, Multi-Product Company (Businesswire) - "DCC-3116: The Company expects to select a recommended Phase 2 dose for expansion cohort(s) for DCC-3116, an investigational switch-control kinase inhibitor of ULK1/2 designed to inhibit autophagy, in 2024; The Company has prioritized the development of DCC-3116 in combination with sotorasib and with QINLOCK and discontinued development of the encorafenib and cetuximab combination cohort prior to enrollment in any clinical studies as well as the two MEK combination cohorts."

Trial status • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Solid Tumor

Deciphera Pharmaceuticals Announces Third Quarter 2023 Financial Results (Businesswire) - "DCC-3084: Expects to submit an Investigational New Drug (IND) application to the FDA for its pan-RAF inhibitor, DCC-3084, by year end 2023. DCC-3009: Expects to submit an IND application to the FDA for its pan-KIT inhibitor, DCC-3009, in the first half of 2024....Total revenue for the third quarter of 2023 was $43.3 million, which includes $41.8 million of net product revenue of QINLOCK and $1.5 million of collaboration revenue compared to $36.0 million of total revenue, including $32.3 million of net product revenue of QINLOCK and $3.7 million of collaboration revenue, for the same period in 2022....Research and development expenses for the third quarter of 2023 were $62.5 million, compared to $47.5 million for the same period in 2022. The increase was primarily due to an increase in clinical study costs for QINLOCK and clinical study costs related to the Phase 1/2 study of DCC-3116."

Commercial • IND • Sales • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

Deciphera Pharmaceuticals Announces Second Quarter 2023 Financial Results (Businesswire) - "Expects to announce top-line results from the MOTION pivotal Phase 3 study of vimseltinib, an investigational, orally administered, potent, and highly selective switch-control kinase inhibitor of CSF1R for the potential treatment of tenosynovial giant cell tumor (TGCT) in the fourth quarter of 2023. Expects to present updated data from the Phase 1/2 study of vimseltinib in the fourth quarter of 2023....Expects to submit an investigational new drug (IND) application to the U.S. Food and Drug Administration (FDA) for DCC-3084 in the fourth quarter of 2023....Expects to submit an IND to the FDA for DCC-3009 in the first half of 2024.... Research and development expenses for the second quarter of 2023 were $58.3 million, compared to $44.9 million for the same period in 2022. The increase was primarily due to an increase in clinical study costs related to the Phase 1/2 study of DCC-3116, the MOTION Phase 3 study and Phase 1 /2 study of vimseltinib, and clinical study costs for QINLOCK."

Commercial • IND • P1/2 data • P3 data: top line • Oncology • Solid Tumor

A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=170 | Recruiting | Sponsor: Deciphera Pharmaceuticals LLC | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Sarcoma • Solid Tumor • BRAF • KIT • PDGFRA

A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov) - P1/2 | N=170 | Not yet recruiting | Sponsor: Deciphera Pharmaceuticals LLC

Combination therapy • Metastases • New P1/2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Sarcoma • Solid Tumor • BRAF • KIT • PDGFRA

"Useful for CRC researchers and patients as well!!! Seeing the DCC-3116 drugs on a slide was an important reminder to me for KRAS, NRAS and BRAF crc patients." (@fireflyann)

Clinical • Colorectal Cancer • BRAF • KRAS

Deciphera Pharmaceuticals Announces First Quarter 2023 Financial Results (Businesswire) - "Expects to initiate new combination escalation studies evaluating DCC-3116 in combination with ripretinib in patients with GIST and in combination with encorafenib and cetuximab in patients with CRC in the second half of 2023....Expects to initiate one or more expansion cohorts in the ongoing Phase 1/2 study of DCC-3116 in the second half of 2023 in combination with the MEK inhibitors trametinib or binimetinib, or the KRAS G12C inhibitor sotorasib....Expects to submit an investigational new drug (IND) application to the FDA for DCC-3084 in the second half of 2023....Expects to submit an IND to the FDA for DCC-3009 in the first half of 2024."

IND • New trial • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Skin Cancer • Solid Tumor

Deciphera Pharmaceuticals Announces First Quarter 2023 Financial Results (Businesswire) - "Research and development expenses for the first quarter of 2023 were $54.8 million, compared to $47.4 million for the same period in 2022. The increase was primarily due to an increase in clinical study costs related to the MOTION Phase 3 study of vimseltinib, the Phase 1/2 study of DCC-3116, and clinical study costs for QINLOCK, including the Phase 3 INTRIGUE study. Non-cash, stock-based compensation was $5.4 million and $6.3 million for the first quarters of 2023 and 2022, respectively."

Commercial • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Lung Cancer • Melanoma • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Sarcoma • Skin Cancer • Soft Tissue Sarcoma • Solid Tumor

DCC-3116, a first-in-class selective ULK1/2 inhibitor of autophagy, in combination with the KIT inhibitor ripretinib induces complete regressions in GIST preclinical models (AACR 2023) - P1/2 | "Approved therapies for GIST include imatinib, sunitinib, regorafenib, ripretinib, and avapritinib. These data demonstrate preclinically that, like other receptor tyrosine kinase inhibitors1, ripretinib activates ULK1/2-mediated autophagy as an ASR resistance mechanism which is inhibited by DCC-3116, providing the rationale to study the combination of DCC-3116 with ripretinib in GIST patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors (NCT04892017)."

Combination therapy • Preclinical • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Solid Tumor

DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with encorafenib and cetuximab in BRAF V600E mutant colorectal cancer models (AACR 2023) - P1/2 | "These preclinical data demonstrate that BRAF inhibitors in combination with EGFR blockade such as E+C activate ULK-mediated autophagy as an ASR resistance mechanism which can be inhibited by DCC-3116, providing the rationale to study the combination of DCC-3116 with E+C in BRAF V600E mutated CRC patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BRAF

Deciphera Pharmaceuticals Announces Eight Presentations Highlighting Discovery Research Programs at the American Association for Cancer Research (AACR) Annual Meeting 2023 (Businesswire) - "...'At the upcoming AACR meeting, we look forward to presenting preclinical data supporting our next Investigational New Drug (IND) candidate, DCC-3084, a potential best-in-class pan-RAF inhibitor that broadly inhibits Class I, II, and III BRAF mutations, BRAF fusions, and BRAF/CRAF heterodimers. In addition, we will present preclinical data on our ULK inhibitor, DCC-3116, in combination with QINLOCK in gastrointestinal stromal tumor (GIST) and in combination with encorafenib and cetuximab in colorectal cancer that strongly support two new dose escalation combination studies that we expect to initiate in the second half of this year'....'We are excited to share initial preclinical data on two new programs, GCN2 and PERK, two novel targets focused on the integrated stress response'...New pan-kit development candidate DCC-3009 for GIST demonstrates potential best-in-class profile with broad coverage of KIT mutations with high selectivity."

New trial • Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Oncology • Sarcoma • Soft Tissue Sarcoma • Solid Tumor

DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with the KRASG12C inhibitor sotorasib resulting in tumor regression in KRAS mutant NSCLC xenograft models (AACR 2022) - P1 | "These data demonstrate a compelling rationale to study DCC-3116 in combination with KRASG12C inhibitors such as sotorasib in NSCLC patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors with documented KRAS, NRAS or BRAF mutations (NCT04892017)."

Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • KRAS • NRAS