Turning Point Therapeutics Presents Initial Clinical Data From Phase 1 SHIELD-1 Study of Novel MET/SRC/CSF1R Inhibitor TPX-0022 at 2020 EORTC-NCI-AACR Symposium - Seite 3

The company anticipates initiating Phase 1 dose expansion after determining the recommended Phase 2 dose. Turning Point plans to discuss the ongoing Phase 1 SHIELD-1 study with the Food and Drug Administration (FDA) to potentially modify the trial into a registrational Phase 1/2 design. The company is targeting initiation of the Phase 2 portion in the second half of 2021, pending FDA feedback. In parallel, based on the SHIELD-1 study initial findings, a combination study with TPX-0022 and an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in patients with EGFR mutated MET-amplified NSCLC is also planned for initiation in the second half of 2021.

Repotrectinib Poster Presentations
In addition, preclinical data for the company’s lead drug candidate repotrectinib were reported in two poster presentations.

The first poster expanded on previous work presented in June at AACR 2020 with additional preclinical data of repotrectinib in combination with the KRAS-G12C inhibitor, AMG-510, in a NSCLC xenograft tumor model. In preclinical studies, repotrectinib significantly enhanced efficacy of AMG-510 and showed a marked survival benefit in a KRAS G12C xenograft model when compared to AMG-510 alone.

Repotrectinib previously showed synergy in preclinical models with AMG-510 and inhibited KRAS G12C tumor cell proliferation, suppressed receptor tyrosine kinase upregulation induced by AMG-510, and reduced KRAS G12C tumor cell cytokine release. Similar results have since been obtained with other KRAS G12C inhibitors.

With the new results presented in a KRAS G12C xenograft tumor model, and previous data shown with repotrectinib in combination with a MEK inhibitor (presented at AACR 2020), the company now plans to initiate a clinical combination study in KRAS mutant NSCLC in mid-2021. Further details on the design will be shared at the time of study initiation.

The second poster showed preclinical studies of repotrectinib as monotherapy and in combination with irinotecan and temozolomide in neuroblastoma cell lines and pediatric patient-derived xenograft (PDX) models. Repotrectinib combined with chemotherapy demonstrated increased anti-tumor activity compared to chemotherapy alone in an ALK-mutant neuroblastoma PDX model.

“With a growing body of supportive preclinical data, we are encouraged by the potentially broader role for repotrectinib across the treatment landscape,” said Dr. Hirmand. “Repotrectinib’s inhibition of the cancer signaling pathways of SRC, FAK and JAK2, and its generally well-tolerated safety profile make it an ideal candidate for combination therapy. We look forward to advancing our combination strategy toward the initiation of clinical studies in 2021.”