UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:
Securities registered pursuant to Section 12(b) of the Act:
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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
Emerging growth company
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 8.01 Other Events.
On April 12, 2022, Turning Point Therapeutics, Inc. (the “Company”) reported positive topline results from the registrational TRIDENT-1 study across all four ROS1-positive advanced non-small cell lung cancer (“NSCLC”) cohorts, as reported by blinded independent central review (“BICR”). In connection with the report of the results, the Company referred to the presentation attached hereto as Exhibit 99.1, which is incorporated herein by reference.
The primary objective of the TRIDENT-1 study is to determine the confirmed objective response rate (“cORR”) based on BICR as assessed by RECIST 1.1, and the key secondary objectives include duration of response (“DOR”), progression free survival (“PFS”) and intracranial activity. The dataset utilizes a February 11, 2022 data cutoff date. The safety analysis included 380 treated patients from the pooled Phase 1 and Phase 2 portions of TRIDENT-1 across all cohorts, of which 287 patients were treated at the Phase 2 dose. The efficacy analyses included pooled patients from Phase 1 across all dose levels with an identified ROS1 fusion by next generation sequencing at baseline and Phase 2 patients. All patients received at least one dose of repotrectinib with at least four months of follow-up, and the majority of responders had at least six months of DOR follow-up.
Pooled Phase 1 and Phase 2 Topline Efficacy Analyses by BICR
ROS1-positive tyrosine kinase inhibitor (“TKI”)-Naïve NSCLC (EXP-1; n=71 (8 from Phase 1 and 63 from Phase 2)):
Table 1. |
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TKI-Naïve (EXP-1) Responder Population |
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Efficacy Parameter |
Patients at Risk |
DOR Landmark |
% DOR ≥ 6 months 95% CI |
35 |
91% (82, 100) |
% DOR ≥ 9 months 95% CI |
29 |
88% (78, 98) |
% DOR ≥ 12 months 95% CI |
21 |
85% (73, 96) |
% DOR ≥ 18 months 95% CI |
8 |
76% (61, 91) |
Patients at Risk: Patients who have reached the specified timepoint without censoring or an event (progression or death).
Table 2. |
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TKI-Naïve (EXP-1) Overall Population |
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Efficacy Parameter |
Patients at Risk |
PFS Landmark |
% PFS ≥ 6 months 95% CI |
46 |
91% (84, 98) |
% PFS ≥ 9 months 95% CI |
37 |
85% (75, 94) |
% PFS ≥ 12 months 95% CI |
26 |
82% (72, 93) |
% PFS ≥ 18 months 95% CI |
11 |
72% (58, 86) |
Patients at Risk: Patients who have reached the specified timepoint without censoring or an event (progression or death).
ROS1-positive TKI-Pretreated NSCLC (EXP-2, EXP-3, and EXP-4; n=100):
TRIDENT-1 Topline Safety Analyses
Repotrectinib was generally well tolerated in a total of 380 patients with a safety and tolerability profile that was consistent with previously reported findings. The most commonly reported treatment emergent adverse event remained dizziness (61% all grade), of which 76% of patients who reported dizziness had a maximum severity of grade 1. The safety profile was comparable among the 287 patients who were treated at the Phase 2 dose.
As previously guided, the Company anticipates discussing the topline BICR data with the U.S. Food and Drug Administration (“FDA”) at a pre-new drug application (“NDA”) meeting this quarter. The Company plans to present detailed study results, including intracranial activity, from the ROS1-positive advanced NSCLC cohorts of the TRIDENT-1 study, at a medical conference in the second half of 2022.
Forward-Looking Statements
Statements contained in this report regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the initial estimated Kaplan-Meier landmark analyses for both duration of response and progression free survival in the TKI-naïve population and related trends, anticipated timing for a pre-NDA meeting with the FDA regarding the topline BICR data for repotrectinib, the efficacy, safety and therapeutic potential of repotrectinib, plans regarding future regulatory submissions, and the regulatory approval path for repotrectinib. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans”, “will”, “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon the Company’s current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with the Company’s business in general, risks and uncertainties related to the impact of the COVID-19 pandemic to the Company’s business and the other risks described in the Company’s filings with the Securities and Exchange Commission (“SEC”), including its annual report on Form 10-K filed with the SEC on February 28, 2022. All forward-looking statements contained in this report speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits.
Exhibit |
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Description |
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99.1 |
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104 |
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Cover Page Interactive Data File (embedded within the Inline XBRL document). |
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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TURNING POINT THERAPEUTICS, INC. |
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Date: |
April 13, 2022 |
By: |
/s/ Brian Sun |
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Brian Sun |
Repotrectinib Topline TRIDENT-1 Phase 1/2 Data in ROS1+ NSCLC Investor Call and Webcast April 13, 2022 Exhibit 99.1
Statements in this Presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our research and clinical development activities, plans and projected timelines, business strategy and plans, regulatory matters, objectives of management for future operations, market size and opportunity, our ability to complete certain milestones and our expectations regarding the relative benefits of our drug candidates versus competitive therapies. Words such as “believe,” “can”, “continue,” “anticipate,” “could,” “estimate,” “plan,” “predict,” “expect,” “intend,” “will,” “may,” “goal,” “upcoming,” “near term”, “milestone”, “potential,” “target” or the negative of these terms or similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include, without limitation: our preclinical studies and clinical trials may not be successful; regulatory authorities, including the U.S. Food and Drug Administration (FDA) may not agree with our interpretation of the data from clinical trials of our drug candidates; we may decide, or regulatory authorities may require us, to conduct additional clinical trials or to modify our ongoing clinical trials; we may experience delays in the commencement, enrollment, completion or analysis of clinical testing for our drug candidates, or significant issues regarding the adequacy of our clinical trial designs or the execution of our clinical trials may arise, which could result in increased costs and delays, or limit our ability to obtain regulatory approval; our drug candidates may not receive regulatory approval or be successfully commercialized; unexpected adverse side effects or inadequate therapeutic efficacy of our drug candidates could delay or prevent regulatory approval or commercialization; the COVID-19 pandemic may disrupt our business and that of third parties on which we depend, including delaying or otherwise disrupting our research and development activities; and we may not be able to obtain additional financing. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this Presentation is given. Other risks and uncertainties affecting us are described more fully in our filings with the Securities and Exchange Commission. We undertake no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made. This Presentation discusses drug candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these drug candidates for the use for which such drug candidates are being studied. Forward-Looking Statements
Today’s Agenda Introduction Athena Countouriotis, M.D., President & CEO Repotrectinib Topline TRIDENT-1 Phase 1/2 Data in ROS1+ NSCLC Mohammad Hirmand, M.D., Chief Medical Officer Q&A Panel Athena Countouriotis, M.D., President & CEO Mohammad Hirmand, M.D., Chief Medical Officer Alexander Drilon, M.D. Chief, Early Drug Development Service, Memorial Sloan Kettering Cancer Center
Data cutoff date: 11-Feb-2022 Safety analysis: 380 patients pooled from Phase 1 + 2 (103 from Phase 1 and 277 from Phase 2) Efficacy analysis: Pooled Phase 1 + 2 patients who received at least one dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up Phase 1: Patients with ROS1 fusion by NGS were included across all dose levels Primary objective: cORR by BICR in each expansion cohort Secondary objectives: DOR, PFS, OS, IC-ORR and CNS-PFS Note: The TRIDENT-1 protocol is being amended to increase the sample size in each of the Phase 2 cohorts to allow for continued access to patients, to a total enrollment across all of the cohorts of approximately 620 patients. Responses included in efficacy analysis confirmed with a subsequent scan at least 28 days later per RECIST 1.1. BICR: blinded independent central review; CNS: central nervous system; cORR: confirmed objective response rate; DOR: duration of response; IC-ORR: intracranial objective response rate; NGS: next generation sequencing; OS: overall survival; PFS: progression free survival TRIDENT-1 Study Design ROS1+ ADVANCED NSCLC NTRK+ ADVANCED SOLID TUMORS EXP-1 ROS1 TKI-naïve (n=55) EXP-2 1 prior ROS1 TKI AND 1 platinum-based chemotherapy (n=60) EXP-3 2 prior ROS1 TKIs AND No prior chemotherapy (n=40) EXP-4 1 prior ROS1 TKI AND No prior chemotherapy (n=60) EXP-5 TRK TKI-naïve (n=55) EXP-6 TRK TKI pretreated (n=40)
EXP-1: ROS1+ TKI-Naïve NSCLC Clinical Activity Note: Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. cORR: confirmed objective response rate; CR: complete response; DOR: duration of response; PR: partial response EXP-1 EXP-2 EXP-3 EXP-4 EXP-5 EXP-6 N=71 cORR (95% CI) CR, n (%) PR, n (%) 79% 4 52 (68, 88) (6) (73) As of the data cutoff, 1 patient in Phase 2 with tumor regression of -38% had an unconfirmed PR (uPR), and remained on treatment awaiting next scan. BEST OVERALL RESPONSE BY BICR (N=71) 3 patients discontinued study treatment before completing any post-baseline scans with target lesion measurements. # = treatment ongoing
ROS1+ TKI-Naïve NSCLC: Duration of Response by Kaplan Meier EXP-1 EXP-2 EXP-3 EXP-4 EXP-5 EXP-6 DOR PARAMETER Repotrectinib¹ (N=56) Rozlytrek (entrectinib)² Xalkori (crizotinib)³ Median DOR 95% CI Not mature 15.7 months (13.9, 28.6) 18.3 months (12.7, NE) DOR Range (months) 1.4+-35.1+ 1.8-42.3 - % DOR ≥ 6 months 95% CI 35 patients at risk 91% (82, 100) 83% (76, 90) - % DOR ≥ 9 months 95% CI 29 patients at risk 88% (78, 98) 75% (67, 84) - % DOR ≥ 12 months 95% CI 21 patients at risk 85% (73, 96) 63% (53, 73) - % DOR ≥ 18 months 95% CI 8 patients at risk 76% (61, 91) Not disclosed - Note: Data not from head-to-head studies. Material presented for summary purposes and no comparative claims are intended. ¹ Median duration of follow-up of 10.2 months. Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. Analyses of repotrectinib DOR at various time points based on Kaplan-Meier estimates, with 95% confidence intervals. ² Dziadziuszko R, et al: J Clin Oncol. (2021). ³ Xalkori (crizotinib) USPI. DOR: duration of response; NE: not estimable
ROS1+ TKI-Naïve NSCLC: Progression Free Survival by Kaplan Meier EXP-1 EXP-2 EXP-3 EXP-4 EXP-5 EXP-6 PFS PARAMETER Repotrectinib¹ (N=71) Rozlytrek (entrectinib)² Xalkori (crizotinib)³ Median PFS 95% CI Not mature 15.7 months (11.0, 21.1) 19.2 months (14.4, NE) PFS Range (months) 0+-40.4+ Not disclosed - % PFS ≥ 6 months 95% CI 46 patients at risk 91% (84, 98) 77% (70, 84) - % PFS ≥ 9 months 95% CI 37 patients at risk 85% (75, 94) 66% (58, 74) - % PFS ≥ 12 months 95% CI 26 patients at risk 82% (72, 93) 55% (47, 64) - % PFS ≥ 18 months 95% CI 11 patients at risk 72% (58, 86) Not disclosed - Note: Data not from head-to-head studies. Material presented for summary purposes and no comparative claims are intended. ¹ Median duration of follow-up of 10.8 months. Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. Analyses of repotrectinib PFS at various time points based on Kaplan-Meier estimates, with 95% confidence intervals. ² Dziadziuszko R, et al: J Clin Oncol. (2021). ³ Shaw A, et al: NEJM (2014). DOR: duration of response; NE: not estimable; PFS: progression free survival
Note: Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. cORR: confirmed objective response rate; CR: complete response; DOR: duration of response; PR: partial response EXP-1 EXP-3 EXP-4 EXP-5 EXP-6 EXP-2 EXP-2: 1 Prior TKI and 1 Platinum-Based Chemotherapy ROS1+ TKI-Pretreated NSCLC Clinical Activity N=26 cORR (95% CI) CR, n (%) PR, n (%) 42% 1 10 (23, 63) (4) (38) DOR N 11 Range (months) 3.6-18.3+ BEST OVERALL RESPONSE BY BICR (N=26) 1 patient discontinued study treatment before completing any post-baseline scans with target lesion measurements. # = treatment ongoing
Note: Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. cORR: confirmed objective response rate; CR: complete response; DOR: duration of response; PR: partial response EXP-1 EXP-4 EXP-5 EXP-6 EXP-2 EXP-3 EXP-3: 2 Prior TKIs and No Prior Chemotherapy ROS1+ TKI-Pretreated NSCLC Clinical Activity BEST OVERALL RESPONSE BY BICR (N=18) N=18 cORR (95% CI) CR, n (%) PR, n (%) 28% 1 4 (10, 54) (6) (22) DOR N 5 Range (months) 1.9+-20.3+ 3 patients discontinued study treatment before completing any post-baseline scans with target lesion measurements. # = treatment ongoing
Note: Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. cORR: confirmed objective response rate; CR: complete response; DOR: duration of response; PR: partial response EXP-1 EXP-3 EXP-5 EXP-6 EXP-2 EXP-4 EXP-4: 1 Prior TKI and No Prior Chemotherapy ROS1+ TKI-Pretreated NSCLC Clinical Activity As of the data cutoff, 2 patients in Phase 2 had an unconfirmed PR (uPR) both with tumor regressions of -47%, both of whom remained on treatment awaiting next scans. BEST OVERALL RESPONSE BY BICR (N=56) 1 patient discontinued study treatment before completing any post-baseline scans with target lesion measurements. # = treatment ongoing N=56 cORR (95% CI) CR, n (%) PR, n (%) 36% 4 16 (23, 50) (7) (30) DOR N 20 Range (months) 1.9+-17.8
Note: Of the TKI-pretreated patients, 10 did not have baseline evaluable information to determine presence of ROS1 G2032R solvent front mutation. Data pooled across the Phase 1 and 2 portions of TRIDENT-1 with a data cutoff of 11-Feb-2022 with responses confirmed per RECIST 1.1 and assessed by blinded independent central review (BICR). Pooled Phase 1 and Phase 2 patients included those who received at least 1 dose of repotrectinib with at least 4 months of follow-up, and the majority of responders had at least 6 months of DOR follow-up. Phase 1 patients had an identified ROS1 fusion by next generation sequencing. cORR: confirmed objective response rate; CR: complete response; DOR: duration of response; PR: partial response EXP-1 EXP-5 EXP-6 ROS1+ TKI-Pretreated NSCLC Clinical Activity Patients with Baseline ROS1 G2032R Solvent Front Mutations EXP-2 EXP-3 EXP-4 BEST OVERALL RESPONSE BY BICR (N=17) 2 patients discontinued study treatment before completing any post-baseline scans with target lesion measurements. # = treatment ongoing N=17 cORR (95% CI) CR, n (%) PR, n (%) 59% 1 9 (33, 82) (6) (53) DOR N 10 Range (months) 1.9+-20.3+
ALL TREATED PATIENTS (N=380) Adverse Reaction TEAES ≥ 15% subjects TRAES ≥ 15% subjects All Grades N (%) Grade 3 N (%) Grade 4 N (%) All Grades N (%) Grade 3 N (%) Grade 4 N (%) Dizziness 230 (60.5) 9 (2.4) 0 209 (55.0) 9 (2.4) 0 Dysgeusia 183 (48.2) 0 0 174 (45.8) 0 0 Constipation 135 (35.5) 1 (0.3) 0 89 (23.4) 0 0 Anemia 124 (32.6) 30 (7.9) 1 (0.3) 77 (20.3) 13 (3.4) 0 Paresthesia 117 (30.8) 3 (0.8) 0 105 (27.6) 3 (0.8) 0 Dyspneaa 106 (27.9) 25 (6.6) 5 (1.3) 26 (6.8) 1 (0.3) 0 Fatigue 93 (24.5) 6 (1.6) 0 63 (16.6) 3 (0.8) 0 Nausea 77 (20.3) 3 (0.8) 0 44 (11.6) 0 0 ALT increased 75 (19.7) 6 (1.6) 0 59 (15.5) 4 (1.1) 0 AST increased 72 (18.9) 7 (1.8) 0 58 (15.3) 3 (0.8) 0 Ataxia 71 (18.7) 0 0 67 (17.6) 0 0 Muscular weakness 71 (18.7) 6 (1.6) 0 38 (10.0) 4 (1.1) 0 Headache 65 (17.1) 1 (0.3) 0 25 (6.6) 0 0 Safety Summary: TRIDENT-1 Phase 1 and Phase 2 Combined Note: Data cutoff of 11-Feb-2022. Grade 4 TRAEs included 2 patients with transient CPK increase and 1 patient with atelectasis. No grade 5 TRAEs reported. a 1 TEAE of grade 5 dyspnea was reported. ALT: Alanine aminotransferase; AST: Aspartate aminotransferase; TEAE: treatment-emergent adverse event; TRAE: treatment-related adverse event Repotrectinib was generally well tolerated Most TRAEs were Grade 1 or 2 The most commonly-reported TEAE remains low-grade dizziness (61%) 76% (175/230) were Grade 1 18 (5%) patients reported ataxia in the absence of dizziness TEAEs of ALT and AST increases were 79% (59/75) and 82% (59/72) Grade 1, respectively Dose modifications due to TEAEs 32% with TEAEs that led to dose reduction 10% with TEAEs that led to drug discontinuation
TRIDENT-1 topline data for ROS1+ TKI-naïve NSCLC cohorts consistent with potential best-in-class profile cORR of 79% (95% CI: 68, 88), not including 1 patient in an uPR awaiting a confirmatory scan 12-month DOR landmark of 85% and PFS landmark of 82% Early encouraging 18-month DOR and PFS landmarks of 76% and 72%, respectively, with medians not mature Encouraging data in ROS1+ TKI-pretreated NSCLC, where there are no approved targeted therapies Generally well tolerated in n=380 patients, with safety and tolerability profile consistent with previously reported findings Pre-NDA meeting with FDA anticipated in 2Q 2022 to discuss data across all four ROS1+ NSCLC cohorts Plan to present detailed study results from the ROS1+ NSCLC cohorts of TRIDENT-1 at an upcoming medical conference in 2H 2022 Summary and Next Steps
Q&A Panel Athena Countouriotis, M.D. President & Chief Executive Officer Mohammad Hirmand, M.D. Chief Medical Officer Alexander Drilon, M.D. Chief, Early Drug Development Service, Memorial Sloan Kettering Cancer Center
Repotrectinib Topline TRIDENT-1 Phase 1/2 Data in ROS1+ NSCLC Investor Call and Webcast April 13, 2022