TP Therapeutics Announces Interim Data from the Phase 1/2 Clinical Trial of Investigational Agent TPX-0005 at ASCO 2018: Data Presented from the Ongoing TRIDENT-1 Study

Preliminary antitumor activity observed in ROS1 fusion-positive NSCLC patients across multiple doses of TPX-0005 with additional responders pending confirmation

Ten Confirmed RECIST Partial Responses (1 NTRK; 7 ROS1 TKI naïve; 2 ROS1 TKI pretreated) with longest duration of treatment of 13.4+ months and 70% of responses ongoing

SAN DIEGO--(BUSINESS WIRE)--TP Therapeutics, Inc., a privately held, clinical-stage biopharmaceutical company developing oncology therapies with a focus on addressing current drug resistance, today announced the first presentation of the interim data from its ongoing Phase 1/2 open-label, dose-escalation trial of TPX-0005, a potent and selective investigational inhibitor for ALK, ROS1, and TRK family.

“TPX-0005 has demonstrated clinically meaningful and durable benefit in patients with ROS1 fusion-positive lung cancers and NTRK fusion-positive tumors,” said Alexander Drilon, M.D., a key investigator in the TRIDENT-1 Study and Clinical Director of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center. “I continue to be encouraged by the preliminary antitumor activity of TPX-0005 and look forward to establishment of the recommended phase 2 dose along with further evaluation of its activity.”

The Phase 1 dose escalation portion of the TRIDENT-1 clinical trial was designed to determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D), as well as preliminary anti-cancer activity, of single agent TPX-0005 in patients with advanced ALK/ROS1/NTRK+ cancers.

As of the April 16, 2018 data cut-off, the study findings showed:

• A total of 72 patients (31 ALK+; 33 ROS1+; and 8 NTRK+) with advanced cancer had been treated across 6 dose levels (40 mg QD; 80 mg QD; 160 mg QD; 240 mg QD; 160 mg BID; and 200 mg BID).
• A range of solid tumors were treated, the most common being NSCLC (83%). Median age was 52.5 years (range 18 – 79); and median # prior TKI therapies were 2 (0-4) in ALK+ patients; 1 (0-3) in ROS1+ patients; and 1 (0-2) in NTRK+ patients

Preliminary Safety Analysis

• TPX-0005 was well tolerated:
  • The most frequent treatment-related AEs (≥ 15%) were dizziness (48.6%; 2.8% Grade 3); dysgeusia (45.8%); paraesthesia (29.2%); constipation (19.4%); and fatigue (18.1%)
  • Four dose-limiting toxicities (DLTs) were observed: Grade 2 or 3 dizziness (n=3: 2 at 160 mg BID; 1 at 240 mg QD) that resolved upon study drug reduction and treatment continued; and Grade 3 dyspnea/hypoxia (n=1 at 160 mg BID) that resolved after study drug discontinuation
  • Neither the MTD nor the RP2D has been reached

Preliminary Efficacy Analysis

• As of the data cutoff, 56 subjects (18 ALK+, 31 ROS1+, 7 NTRK+) had both a baseline and at least 1 post-baseline tumor assessment and are evaluable for tumor response by investigators
  • 18 Evaluable ALK+ subjects: 14 TKI-refractory NSCLC who were heavily pretreated
    • No PR or CR to date; 4 subjects had stable disease between 83 -165 days
  • 31 Evaluable ROS1+ subjects: 29 ROS1+ NSCLC subjects
    • 10 TKI-naïve and 19 TKI-refractory NSCLC: median # prior TKIs = 1 (0-3)
      • TKI-naïve subjects, confirmed PR rate = 70% (7/10), with 1 additional PR to be confirmed
        • 90% remaining on treatment
      • TKI-refractory subjects, there have been 2 confirmed PRs with 1 additional PR to be confirmed and 6 durable stable disease with treatment duration more than 6 months
        • A crizotinib-refractory CD74-ROS1+ NSCLC subject with solvent front mutation ROS1 G2032R achieved a cPR with duration of treatment 8.0+ months
        • 53% remaining on treatment
  • 7 Evaluable NTRK+ subjects: 2 were NTRK fusion-negative by NGS; and 2 NTRK+ had glioblastoma multiforme
    • A cPR (-82% in target lesions) observed in a TKI-refractory subject with mammary analogue secretory carcinoma (MASC) with solvent front mutation ETV6-TRKC G623E with a treatment duration of 13.2+ months
    • Another PR in a TKI-refractory subject with cholangiocarcinoma

“The team at TP Therapeutics is proud to have contributed to this first presentation of the interim Phase 1 data from the ongoing TRIDENT-1 Study,” said Athena Countouriotis, M.D., Executive Vice President and Chief Medical Officer of TP Therapeutics. “We look forward to further data updates from this study, and discussions with the FDA related to the development of TPX-0005.”

About TPX-0005

TPX-0005 is a potent and orally bioavailable investigational small molecule kinase inhibitor for ALK, ROS1, and TRK family. The clinical benefits of targeting ALK, ROS1, or TRK fusion kinase have been demonstrated with multiple kinase inhibitors already approved for the treatment of ALK+ non-small cell lung cancer (NSCLC), in addition to crizotinib for ROS1+ NSCLC, and larotrectinib and entrectinib in clinical studies for TRK+ cancers. The successes of these therapies are overshadowed by the development of acquired resistance. The acquired solvent front mutations including ALK G1202R, ROS1 G2032R, TRKA G595R and TRKC G623R render a common clinical resistance to the current ALK, ROS1, and TRK inhibitors. TPX-0005 is a potent kinase inhibitor against wildtype and mutated ALK, ROS1 and TRK family kinases, especially the clinically significant solvent front mutations, gatekeeper mutations, and emerging compound mutations after multiple line treatments. TPX-0005 may provide a new opportunity to inhibit the abnormal signaling of ALK, ROS1, or TRK family in solid malignancies, and overcome multiple resistance mechanisms seen in refractory patients. TPX-0005 is currently being evaluated in a Phase 1/2, open-label, multi-center, first-in-human study of the safety, tolerability, pharmacokinetics and anti-tumor activity in patients with advanced solid tumors harboring ALK, ROS1, or NTRK1-3 rearrangements (TRIDENT-1, NCT03093116). For additional information about TPX-0005 trial, please refer to www.clinicaltrials.gov. Interested patients and physicians can also contact the TP Therapeutics Oncology Clinical Trial Hotline at 1-858-276-0005 or email [e-mail].

About TP Therapeutics, Inc.

TP Therapeutics, Inc. (TP) is a clinical-stage structure-based oncology drug design company founded in October 2013 by Dr. J. Jean Cui, the lead inventor of Pfizer’s oncology drug crizotinib and lorlatinib. The TP team is focused on the design and development of novel chemical entities within oncology for established oncogene drivers with high incidence of secondary resistance mutations; newly identified disease-driven targets; and potential targets regulating the tumor microenvironment and tumor immunity. For more information, please visit us at www.tptherapeutics.com.