Taletrectinib / AB-106

ROS1 oncogenic fusions are observed in ~1-2% non-small cell lung cancer (NSCLC) patients (J Thorac Oncol  2017). There are more than 20,000 newly diagnosed patients with ROS1 fusion-positive NSCLC each year. ROS1 fusions are observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers. The incidence of CNS metastasis in ROS1 fusion-positive NSCLC patients at the time of diagnosis ranges from 20% to mid-30% while the incidence of CNS metastasis can be as high as mid 50% range, post-crizotinib treatment (Lung Cancer 2019). First generation ROS1 tyrosine kinase inhibitors (TKIs), crizotinib and entrectinib, have received U.S. FDA approval for advanced ROS1 fusion-positive NSCLC.

There are currently no FDA approved drugs for patients who do not respond to these first generation ROS1 inhibitors or have resistance. Resistance to first-generation ROS1 inhibitors will ultimately occur with on-target resistance such as with acquired ROS1 G2032R solvent front mutations, one of the most common treatment-resistant mutations.

TALETRECTINIB / AB-106 (ROS1 INHIBITOR)

Our next-generation ROS1 inhibitor, taletrectinib, has demonstrated excellent potency against crizotinib resistance tumors. Taletrectinib also has the advantage of addressing brain metastasis by penetrating the blood brain barrier. The compound has reported a strong safety profile in ROS1 fusion-positive NSCLC patients. The selective inhibition of ROS1 over TRKB by taletrectinib (Nature Communications 2019) helps significantly reduce TRKB-related CNS adverse events.

Preliminary results from our Phase 2 trial (TRUST, NCT04395677 ) in China, as of June 16 2021, reported:

  • ORR 90.5% (19/21)  in ROS1 TKI naïve patients
  • ORR 43.8% (7/16) in crizotinib failure patients
  • ORR 75% (3/4) in patients with crizotinib-resistant G2032R mutation
  • intracranial ORR 83.3% (5/6) in brain metastatic patients
  • good safety profile with few CNS adverse events

A second global Phase 2 trial (TRUST-II, NCT04919811) is actively enrolling patients at clinical sites in US, Japan, Korea, Europe, Canada and China.

Taletrectinib Efficacy on Crizotinib Naïve

  • A patient with ROS1 fusion positive NSCLC
  • Received taletrectinib at 600 mg QD
  • Achieved partial response (PR) by investigator evaluation at week 7

Taletrectinib Efficacy on Crizotinib Failure

  • A patient with ROS1 fusion positive NSCLC and failed crizotinib treatment
  • Received taletrectinib at 600 mg QD
  • Achieved partial response (PR) by investigator evaluation at week 13

Taletrectinib Efficacy on Crizotinib Failure with Resistant Mutation G2032R

  • A patient with ROS1 fusion positive NSCLC and failed crizotinib treatment with  G2032R
  • Received taletrectinib at 600 mg QD
  • Achieved partial response (PR) by investigator evaluation at week 7

Taletrectinib Efficacy on Brain Metastasis

  • A patient with ROS1 fusion positive NSCLC and brain metastasis
  • Received taletrectinib at 600 mg QD
  • Achieved intracranial partial response (PR) by investigator evaluation at week 7