Form 8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of earliest event reported): August 19, 2020

 

 

TURNING POINT THERAPEUTICS, INC.

(Exact name of Registrant as Specified in Its Charter)

 

 

 

Delaware   001-38871   46-3826166

(State or Other Jurisdiction

of Incorporation)

 

(Commission

File Number)

 

(IRS Employer

Identification No.)

 

10628 Science Center Drive, Suite 200, San Diego, CA   92121
(Address of Principal Executive Offices)   (Zip Code)

Registrant’s Telephone Number, Including Area Code: (858) 926-5251

N/A

(Former Name or Former Address, if Changed Since Last Report)

 

 

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 (see General Instructions A.2. below):

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange

on which registered

Common Stock, $0.0001 par value per share   TPTX   The Nasdaq Stock Market LLC

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 or Rule 12b-2 of the Securities Exchange Act of 1934.

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.

Beginning on August 19, 2020, representatives of Turning Point Therapeutics, Inc. (the “Company”) will be providing presentation materials (the “Presentation”) to certain interested parties. A copy of the Presentation is attached hereto as Exhibit 99.1 and incorporated herein by reference.

On August 19, 2020, the Company issued a press release providing program updates, including reporting early interim data from the registrational Phase 2 TRIDENT-1 study of the Company’s lead drug candidate, repotrectinib, and announcing recent regulatory feedback from the U.S. Food and Drug Administration on the TRIDENT-1 study that may accelerate the timelines to potential approval for repotrectinib. A copy of the press release is attached hereto as Exhibit 99.2 and is incorporated herein by reference.

 

Item 9.01

Financial Statements and Exhibits.

(d) Exhibits.

 

Exhibit

Number

   Description
99.1    Presentation Materials of Turning Point Therapeutics, Inc.
99.2    Press Release issued by Turning Point Therapeutics, Inc. on August 19, 2020


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.

 

    TURNING POINT THERAPEUTICS, INC.
Date: August 19, 2020     By:  

/s/ Annette North

      Annette North
      Executive Vice President and General Counsel
EX-99.1

Slide 1

TRIDENT-1 Phase 2 Study of Repotrectinib: Early Interim Data Update August 19, 2020 Exhibit 99.1


Slide 2

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


Slide 3

Our Vision Drives our Strategy Pipeline Expansion Clinical Excellence Leadership in Precision Oncology Potential for Best-in-Class Products Addressing Patients with High Unmet Need in TKI-Naïve and Resistance Settings Deep Oncology Development Expertise Rapid Clinical Proof-of-Concept Data Therapeutic Area Focus with Indication Expansion with Synergistic Combinations Mine Existing Macrocyclic Scaffolds New Discovery against Novel or Validated Targets TKI-Pretreated TKI-Naive NSCLC


Slide 4

Repotrectinib: Potential Best-in-Class ROS1 and NTRK Targeted Therapy in TKI-Naïve and Treatment Resistance Settings Highly potent, structurally differentiated: small (low molecular weight), compact, with a rigid 3D macrocycle Designed to bind completely inside the ATP pocket even in the presence of solvent front or gatekeeper mutations Potential to address resistance from prior lines of TKI therapy May also prevent or delay the emergence of new resistant mutations


Slide 5

¹ Based on Phase 1 data as of July 22, 2019 cutoff; TKI-Naïve patients treated at multiple repotrectinib dose levels; TKI-pretreated patients with 1 prior TKI and 1 prior chemotherapy treated at repotrectinib dose of 160 mg or above; intracranial patients with 1 prior TKI and at least one prior line of chemotherapy treated at multiple repotrectinib dose levels. ² Xalkori (crizotinib) USPI; ³ Shaw, Alice T et al. “Crizotinib in ROS1-rearranged non-small-cell lung cancer.” The New England journal of medicine vol. 371,21 (2014): 1963-71. doi:10.1056/NEJMoa1406766. 4 Roche press release (Aug. 3, 2020), “Rozlytrek, Roche’s first tumour-agnostic therapy, approved in Europe for people with NTRK fusion-positive solid tumours and for people with ROS1-positive, advanced non-small cell lung cancer”; Rozlytrek (entrectinib) USPI. In the Rozlytrek (entrectinib) European SmPC, in a total of 161 ROS1+ NSCLC patients, who had a minimum of 6 months of follow-up, ORR was 67% (59, 74); DOR was 63% at 12-months; and PFS was 55% at 12 months. ROS1+ NSCLC Repotrectinib1 Xalkori (Crizotinib)2 Rozlytrek (Entrectinib)4 TKI-Naïve (n=11) TKI-Pretreated (n=7) TKI-Naïve (n=50) TKI-Naïve (n=94) Confirmed ORR (cORR) 91% (95% CI: 59-100) 57% (95% CI: 18 - 90) 66% (95% CI: 51-79) 73% (95% CI: 63-82) Median Duration of Response (mDOR) 23.1 months (95% CI: 5.6-NR) ND 18.3 months (95% CI: 12.7-NR) 16.5 months (95% CI: 14.6-28.6) Median Progression Free Survival (mPFS) 24.6 months (95% CI: 7.2-NR) ND 19.2 months3 (95% CI: 14.4-NR) 16.8 months (95% CI: 12.0-21.4) Intracranial ORR (IC-ORR) 100% (n=3) (95% CI: 29-100) 75% (n=4) (95% CI: 19-99) Not Reported 79% (95% CI: 58-93) Safety Generally Well Tolerated No Grade 3 or Grade 4 ALT / AST Elevations No QT Prolongation Hepatotoxicity Interstitial Lung Disease (ILD) QT Prolongation, Bradycardia Severe Visual Loss Congestive Heart Failure CNS Effects Skeletal Fractures Hepatotoxicity, Hyperuricemia QT Prolongation Vision Disorders Lead Candidate Repotrectinib: Best-in-Class Potential in ROS1+ NSCLC


Slide 6

Pivotal Phase 2 TRIDENT-1 Study Ongoing Single-agent repotrectinib studied in six cohorts (n=~320)  Starting dose at 160 mg QD, which may be increased after 14 days to 160 mg BID based on tolerability Fast Track Designation granted for TKI-naïve and TKI-pretreated ROS1+ advanced NSCLC patients *Patients previously treated with 2 prior TKIs and no prior chemotherapy enrolled under the initial protocol will be included in the safety analysis and analyzed independently for efficacy in a separate “other” cohort. ROS1+ Advanced NSCLC Pivotal Cohorts (n=195) ROS1+ Adv. NSCLC Exploratory Cohort (up to n=30) NTRK+ Advanced Solid Tumors Pivotal Cohorts (n=95) EXP-1 ROS1 TKI-Naïve (n=55) EXP-2 1 Prior ROS1 TKI AND 1 Platinum-Based Chemotherapy (n=100) EXP-3* 2 Prior ROS1 TKIs AND 1 Platinum-Based Chemotherapy (n=40) EXP-4 1 Prior ROS1 TKI AND No Prior Chemotherapy (up to n=30) EXP-5 TRK TKI-Naive (n=55) EXP-6 TRK TKI-Pretreated (n=40) Phase 2 Primary Objective cORR by BICR in each expansion cohort Phase 2 Secondary Objectives DOR, PFS, and OS IC-ORR and CNS-PFS Ongoing Safety Evaluation by Independent Data Monitoring Committee


Slide 7

TRIDENT-1 Phase 2 Study: Early Interim Data Summary N=39 Patients1 Data cutoff date, 10 July 2020 Analysis includes EXP-1, EXP-2, EXP-3, EXP-4, EXP-6, Other Enrolled across 6 countries All patients were followed for at least one post-baseline scan evaluated by RECIST v1.1 by Investigator Responses (CR or PR) were confirmed with a subsequent scan at least 28 days later Of n=26 ROS1+ TKI pretreated patients, 85% received prior crizotinib Median (range) duration of treatment across all cohorts = 3.7 (0.7 – 8.2+) months Median (range) follow-up time across all cohorts = 3.6 (0.4 - 7.4+) months 1 Represents the first 39 treated patients


Slide 8

TRIDENT-1 Phase 2 Study: Early Interim Data Summary Phase 2 (N=391) Cohort ROS1+ TKI-Naïve (EXP-1: N=7) ROS1+ TKI Pretreated 1 Prior TKI with prior platinum-based chemotherapy (EXP-2: N=5) ROS1+ TKI Pretreated 1 Prior TKI without prior platinum-based chemotherapy (EXP-4: N=6) ROS1+ TKI-Pretreated: 2 Prior TKIs without prior platinum-based chemotherapy (EXP-Other3: N=5) NTRK+ TKI-Pretreated (EXP-6: N=6) Overall Response Rate (95% CI) 6 (86%2) (42 – 100) 2 (40%) (5 – 85) 4 (67%) (22 – 96) 2 (40%) (5 – 85) 3 (50%) (12 – 88) Duration of Response (Range) (months) 0.9+ - 2.0+ 4.5 - 5.6+ 1.0+ – 5.7+ 1.9+ – 1.9+ 1.7+ – 3.6+ # of Subjects Titrating from 160 QD to 160 BID Dosing 6 (86%) 5 (100%) 5 (83%) 4 (80%) 6 (100%) 1 In EXP-3 (Two prior TKIs with prior chemotherapy; N=10): No objective responses observed. EXP-3 to be modified to remove prior chemotherapy 2 The seventh patient achieved an unconfirmed PR after the data cutoff date and remains on treatment awaiting a confirmatory scan. uPR is not counted in ORR calculations 3 Represents the planned modified EXP-3 cohort of patients previously treated with 2 prior TKIs without prior chemotherapy Phase 2 Data cutoff of 10 July 2020, responses by Physician Assessment confirmed per RECIST 1.1


Slide 9

TRIDENT-1 Efficacy Overview – Early Phase 2 Data Compared to Phase 1 Phase 2 (N=391) Efficacy by Physician Assessment ROS1+ TKI-Naïve (EXP-1: N=7) ROS1+ TKI Pretreated 1 Prior TKI with prior platinum-based chemotherapy (EXP-2: N=5) ROS1+ TKI Pretreated 1 Prior TKI without prior platinum-based chemotherapy (EXP-4: N=6) ROS1+ TKI Pretreated 2 Prior TKI without prior platinum-based chemotherapy (EXP-Other3: N=5) NTRK+ TKI-Pretreated (EXP-6: N=6) Overall Response Rate (95% CI) 6 (86%2) (42 – 100) 2 (40%) (5 – 85) 4 (67%) (22 – 96) 2 (40%) (5 – 85) 3 (50%) (12 – 88) Duration of Response (Range) (months) 0.9+ - 2.0+ 4.5 - 5.6+ 1.0+ – 5.7+ 1.9+ – 1.9+ 1.7+ – 3.6+ Phase 1 (N=334): All Dose Levels Studied Efficacy by BICR ROS1+ TKI-Naïve (N=11) ROS1+ TKI Pretreated 1 Prior TKI with prior platinum-based chemotherapy (N=14) ROS1+ TKI Pretreated 1 Prior TKI without prior platinum-based chemotherapy (N=4) ROS1+ TKI Pretreated 2 Prior TKI without prior platinum-based chemotherapy (N=1) NTRK+ TKI-Pretreated (N=3) Overall Response Rate (95% CI) 10 (91%) (59 - 100) 5 (36%) (13 - 65) 2 (50%) (7 – 93) 0 1 (33%) (1 – 91) Duration of Response (Range) (months) 3.7+ - 23.3+ 2.7+ - 13.0 0.8+ - 5.5+ NA 9.8 1 In EXP-3 (Two prior TKIs with prior chemotherapy; N=10): No objective responses observed. EXP-3 to be modified to remove prior chemotherapy 2 The seventh patient achieved an unconfirmed PR after the data cutoff date and remains on treatment awaiting a confirmatory scan. uPR is not counted in ORR calculations 3 Represents the planned modified EXP-3 cohort of patients previously treated with 2 prior TKIs without prior chemotherapy 4 Phase 1 dataset previously reported 4 patients treated with 3 prior TKIs and 6 patients who had 2 TKIs and prior chemotherapy Phase 2 Data cutoff of 10 July 2020, Phase 1 Data cutoff of 22 July 2019


Slide 10

ROS1+ TKI Naïve Advanced NSCLC Patients in TRIDENT-1 (EXP-1 + Phase 1) ^Patient achieved an unconfirmed partial response after the data cutoff date and remains on treatment awaiting a confirmatory scan. uPR is not counted in cORR calculation. Phase 2 Data cutoff of 10 July 2020, responses confirmed by Physician Assessment Phase 1 Data cutoff of 22 July 2019, responses confirmed by Blinded Independent Central Review (BICR) Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib Confirmed ORR (cORR) (95% CI) Duration of Response 0.9+ - 2.0+ months (range) n=6 0.9+ – 17.6+ months (range) n=12 86% (42 – 100) 86% (57 – 98) Phase 2 (n=7) Phase 1+2 (n=14)


Slide 11

ROS1+ TKI-Pretreated Advanced NSCLC Patients in TRIDENT-1: One Prior TKI with Prior Platinum-Based Chemotherapy (EXP-2 + Phase 1) Patient with cCR had a G2032R solvent-front mutation after prior treatment with entrectinib Phase 2 Data cutoff of 10 July 2020, responses confirmed by Physician Assessment Phase 1 Data cutoff of 22 July 2019, responses confirmed by Blinded Independent Central Review (BICR) Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib Confirmed ORR (cORR) (95% CI) Duration of Response 40% (5 – 85) 4.5 – 5.6+ months (range) n=2 50% (21 - 79) 2.7+ - 11.1 months (range) n=6 Phase 2 (n=5) Phase 1+2 (n=12)


Slide 12

ROS1+ TKI-Pretreated Advanced NSCLC Patients in TRIDENT-1: One Prior TKI without Prior Platinum-Based Chemotherapy (EXP-4 + Phase 1) Phase 2 Data cutoff of 10 July 2020, responses confirmed by Physician Assessment Phase 1 Data cutoff of 22 July 2019, responses confirmed by Blinded Independent Central Review (BICR) Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib Confirmed ORR (cORR) (95% CI) Duration of Response 67% (22 – 96) 1.0+ - 5.7+ months (range) n=4 67% (30 – 93) 0.8+ - 5.7+ months (range) n=6 Phase 2 (n=6) Phase 1+2 (n=9)


Slide 13

ROS1+ TKI-Pretreated Advanced NSCLC Patients in TRIDENT-1 : Two Prior TKIs without Prior Platinum-Based Chemotherapy (EXP Other + Phase 1) Phase 2 Data cutoff of 10 July 2020, responses confirmed by Physician Assessment Phase 1 Data cutoff of 22 July 2019, responses confirmed by Blinded Independent Central Review (BICR) Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib Confirmed ORR (cORR) (95% CI) Duration of Response 40% (5 – 85) 1.9+ – 1.9+ months (range) n=2 33% (4 – 78) 1.9+ - 1.9+ months (range) n=2 Phase 2 (n=5) Phase 1+2 (n=6) * Phase 2 patient with no change in target lesions, but with new lesions ** One patient in Phase 2 did not have post-baseline target lesion measurements and therefore is not on the waterfall plot


Slide 14

NTRK+ TKI-Pretreated Advanced Solid Tumor Patients in TRIDENT-1 (EXP-6 + Phase 1) Confirmed ORR (cORR) (95% CI) Duration of Response Phase 2 Data cutoff of 10 July 2020, responses confirmed by Physician Assessment per RECIST Phase 1 Data cutoff of 22 July 2019, responses confirmed by Blinded Independent Central Review (BICR) Phase 1 data includes only patients treated at or above the Phase 2 recommended dose of repotrectinib 50% (12 – 88) 1.7+ – 3.6+ Months (range) n=3 43% (10 – 82) 1.7+– 3.6+ months (range) n=3 Phase 2 (n=6) Phase 1+2 (n=7)


Slide 15

All Treated Patients (n=39) TEAEs (≥10% of patients) TRAEs All Grades Grade 3 Grade 4 Grade 31 Grade 4 Adverse Event n (%) n (%) n (%) n (%) n (%) Dizziness 24 (61.5) – – --- – Fatigue 15 (38.5) 1 (2.6) – 1 (2.6) – Constipation 13 (33.3) – – – – Dysgeusia 13 (33.3) – – – – Dyspnea 11 (28.2) 1 (2.6) – – – Paresthesia 8 (20.5) – – – – Muscular weakness 7 (17.9) 1 (2.6) – – – Nausea 7 (17.9) – – – – Pain 5 (12.8) – – – – Anemia 4 (10.3) 2 (5.1) – 2 (5.1) – Aspartate aminotransferase increased 4 (10.3) – – – – Hypoesthesia oral 4 (10.3) – – – – Sensitive skin 4 (10.3) – – – – Generally well-tolerated Most treatment emergent adverse events (TEAEs) and treatment-related adverse events (TRAEs) were Grade 1 or 2 No Grade 4 or Grade 5 TRAEs The most commonly reported TEAE was low grade dizziness 83% (20/24) were Grade 1 No cases of dizziness have led to treatment discontinuation No Grade 3 or Grade 4 treatment-related ALT/AST elevations reported Phase 2 Safety Summary: Treatment-Emergent and Treatment-Related AEs Data cut-off date of July 10, 2020. 1 Additional Grade 3 TRAEs:: depressed level of consciousness (n=1), neutrophil count decreased (n=2), and lymphopenia (n=1)


Slide 16

Planned Updates to Phase 2 TRIDENT-1 Study Design Planned Updates Noted in Yellow Boxes 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-Naive (n=55) EXP-6 TRK TKI-Pretreated (n=40) Phase 2 Primary Objective cORR by BICR in each expansion cohort Phase 2 Secondary Objectives DOR, PFS, and OS IC-ORR and CNS-PFS Study Updates Following FDA Feedback: Pooling Phase 1 Data at or above Recommended Dose with Phase 2 Data Plan to Decrease EXP-2 to n=60, Increase EXP-4 to n=60, with Interim Analyses at ~30 Patients in Each Follow-up of 6 months in EXP-2, EXP-4, EXP-6; 9 months in EXP-5 *Patients with prior chemotherapy to no longer be enrolled in this cohort


Slide 17

TRIDENT-1 Phase 2 Data Update – Key Takeaways Early, interim data in 39 patients from ongoing Phase 2 study reaffirm repotrectinib as potentially best-in-class therapy Wider global population: Patients enrolled across 6 countries as compared to 2 countries in the Phase 1 portion Dose-titration approach: showing 90% titrate up from daily to twice daily without new safety concerns Generally consistent adverse event profile to prior update in Phase 1 portion of TRIDENT-1 Recent feedback from FDA may provide faster path to potential approval Goal to achieve full site activation in early 2021 and provide update on overall study timeline

EX-99.2

Exhibit 99.2

 

LOGO

FOR IMMEDIATE RELEASE

Contact:

Jim Mazzola

jim.mazzola@tptherapeutics.com

858-342-8272

TURNING POINT THERAPEUTICS REPORTS EARLY INTERIM DATA FROM REGISTRATIONAL PHASE 2 TRIDENT-1 STUDY OF REPOTRECTINIB, PROVIDES REGULATORY UPDATE

 

   

ROS1+ TKI-Naïve Non-Small Cell Lung Cancer Confirmed Objective Response Rate is 86 Percent

 

   

ROS1+ TKI-Pretreated Non-Small Cell Lung Cancer with One Prior TKI and Prior Chemotherapy, Confirmed Objective Response Rate is 40 Percent

 

   

ROS1+ TKI-Pretreated Non-Small Cell Lung Cancer with One Prior TKI without Prior Chemotherapy, Confirmed Objective Response Rate is 67 Percent

 

   

NTRK+ TKI-Pretreated Advanced Solid Tumors Confirmed Objective Response Rate is 50 Percent

 

   

Recent FDA Feedback on TRIDENT-1 Study May Provide Faster Path to Potential Approval

 

   

Conference Call Scheduled for 8:00 a.m. EDT

SAN DIEGO, Aug. 19, 2020 – Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, today reported early interim data from the registrational Phase 2 TRIDENT-1 study of lead drug candidate, repotrectinib, and announced recent regulatory feedback from the Food and Drug Administration (FDA) on the TRIDENT-1 trial design.

“We are very encouraged by the early interim data from the Phase 2 TRIDENT-1 study as they reaffirm our belief that repotrectinib has the potential to be the best-in-class treatment for patients with ROS1- or NTRK-driven tumors, including patients who are TKI-naïve and TKI-pretreated,” said Athena Countouriotis, M.D., president and chief executive officer. “Additionally, we recently received FDA feedback that may provide

 

1


a faster path to potential approval, including pooling of patients from the Phase 1 portion of the study treated at the recommended dose of repotrectinib with patients treated in the Phase 2 portion, and cohort sample size modifications. Hence, we are modifying the TRIDENT-1 study sample sizes and adding new interim analyses that may support approval into two of our ROS1-positive TKI-pretreated patient cohorts. We now anticipate providing an update in early 2021 on the overall study timelines.”

Early Interim Phase 2 Data from TRIDENT-1 Study

The early Phase 2 TRIDENT-1 dataset utilizing a July 10, 2020 data cutoff includes the first 39 treated patients who have had at least one post-baseline scan. Responses were confirmed with a subsequent scan at least 28 days later per RECIST 1.1 and were determined by physician assessment. Patients were enrolled across six countries.

Phase 2 Preliminary Efficacy Analysis (n=39)

 

   

Across all cohorts reported, median follow-up was 3.6 months (range: 0.4 – 7.4+), and median duration of treatment was 3.7 months (range: 0.7-8.2+)

 

   

In the ROS1-positive TKI-naïve non-small cell lung cancer (NSCLC) population (EXP-1: n=7):

 

   

Six patients achieved a confirmed response for an Objective Response Rate (ORR) of 86 percent. The duration of response ranged from 0.9+ to 2.0+ months and all patients who achieved a response remained in a response at the time of the data cutoff.

 

   

Since the July 10 data cutoff, the seventh patient in this cohort has achieved an unconfirmed partial response and remains on treatment awaiting a confirmatory scan.

 

   

In the ROS1-positive NSCLC population pretreated with one prior TKI with prior chemotherapy (EXP-2: n=5):

 

   

Two patients achieved a confirmed response for an ORR of 40 percent. The durations of response were 4.5 and 5.6+ months at the time of the data cutoff.

 

   

In the ROS1-positive NSCLC population pretreated with one prior TKI without prior chemotherapy (EXP-4: n=6):

 

   

Four patients achieved a confirmed response for an ORR of 67 percent. The duration of response ranged from 1.0+ to 5.7+ months with all four patients remaining in a response at the time of the data cutoff.

 

   

In the ROS1-positive NSCLC population pretreated with two prior TKIs with prior chemotherapy (EXP-3: n=10):

 

   

No objective responses were observed within this heavily pretreated fourth-line patient population, yet five patients achieved stable disease.

 

2


   

The company recently recommended to the study’s data monitoring committee (DMC) that expansion cohort three (EXP-3) be modified to remove the requirement for prior chemotherapy based on limited activity to date in this fourth-line patient cohort. The company’s intent is to only support third-line patients in this cohort going forward and to preserve the opportunity to evaluate these patients as the treatment landscape changes with less chemotherapy use. The DMC recommended the study proceed and agreed with the recommended change to cohort three.

 

   

In the ROS1-positive NSCLC population pretreated with two prior TKIs without prior chemotherapy (patients enrolled under the initial protocol and analyzed for efficacy in a separate cohort, EXP-Other: n=5):

 

   

Two patients achieved a confirmed response for an ORR of 40 percent. Both patients remained in a response with a duration of 1.9+ months at the time of the data cutoff.

 

   

In the NTRK-positive TKI-pretreated solid tumor population (EXP-6: n=6):

 

   

Three patients achieved a confirmed response for an ORR of 50 percent. The duration of response ranged from 1.7+ to 3.6+ months with all three patients remaining in a response at the time of the data cutoff.

Data from the Phase 1 (at all doses studied) and Phase 2 of the TRIDENT-1 study are summarized in the table below.

 

TRIDENT-1 Study of

Repotrectinib

(Phase 2 Cohorts)

   Phase 1
July 22, 2019
Data Cutoff
All doses studied, BICR
   Phase 2
July 10, 2020
Data Cutoff
Phase 2 Dose, PI assessment
   ORR    95% CI    ORR    95% CI

ROS1+ TKI-Naïve (EXP-1)

   91%

(10/11)

   (59-100)    86%1

(6/7)

   (42-100)

ROS1+ TKI-Pretreated 1-prior TKI, with prior platinum-based chemotherapy (EXP- 2)

   36%

(5/14)

   (13-65)    40%

(2/5)

   (5-85)

ROS1+ TKI-Pretreated, without prior platinum-based chemotherapy (EXP-4)

   50%

(2/4)

   (7-93)    67%

(4/6)

   (22-96)

ROS1+ TKI-Pretreated 2-prior TKIs, without prior platinum-based chemotherapy 2 (EXP- Other)

   0%

(0/1)

   NA    40%

(2/5)

   (5-85)

NTRK TKI-Pretreated (EXP-6)

   33%

(1/3)

   (1-91)    50%

(3/6)

   (12-88)

 

1 

Since the July 10th data cutoff, the seventh patient in this cohort has achieved an unconfirmed partial response and remains on treatment awaiting a confirmatory scan.

2 

Represents the planned modified EXP-3 cohort of patients previously treated with 2 prior TKIs without prior chemotherapy. In EXP-3 (Two prior TKIs with prior chemotherapy; N=10): No objective responses observed.

 

3


Data pooled from the Phase 1 (patients dosed at or above the Phase 2 dose) and Phase 2 portions of the TRIDENT-1 study are summarized in the table below.

 

TRIDENT-1 Study of

Repotrectinib

(Phase 2 Cohorts)

   Phase 1 + 2 TRIDENT-1 Data Combined
(Phase 1 patients  dosed at or above the Phase 2 dose)
   ORR    95% CI

ROS1+ TKI-Naïve (EXP-1)

   86%1

(12/14)

   (57-98)

ROS1+ TKI-Pretreated 1-prior TKI, with prior platinum-based chemotherapy (EXP-2)

   50%

(6/12)

   (21-79)

ROS1+ TKI-Pretreated 1-prior TKI without prior platinum-based chemotherapy (EXP-4)

   67%

(6/9)

   (30-93)

ROS1 TKI-Pretreated 2-prior TKIs, without prior platinum-based chemotherapy 2 (EXP-Other)

   33%

(2/6)

   (4-78)

NTRK TKI-Pretreated (EXP-6)

   43%

(3/7)

   (10-82)

 

1 

Since the July 10th data cutoff, one additional Phase 2 patient achieved an unconfirmed partial response and remains on treatment awaiting a confirmatory scan.

 

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Represents the planned modified EXP-3 cohort of patients previously treated with 2 prior TKIs without prior chemotherapy. In EXP-3 (Two prior TKIs with prior chemotherapy; N=10): No objective responses observed.

Preliminary Safety Analysis (n=39)

 

   

A total of 39 ROS1- and NTRK-positive patients were treated with repotrectinib at a starting dose of 160 mg daily (QD), with 90 percent of patients escalating after 14 days to 160 mg twice daily (BID) per the study defined dose titration approach.

 

   

Repotrectinib was generally well tolerated. The majority of treatment emergent adverse events (TEAEs) were Grade 1 or 2. The TEAEs (any Grade) found in greater than 25 percent of patients were dizziness (62%), fatigue (39%), constipation (33%), dysgeusia (33%), and dyspnea (28%). There were no Grade 3 cases of dizziness and no cases of dizziness leading to treatment discontinuation.

 

   

Additionally, the majority of treatment related adverse events (TRAEs) were Grade 1 or 2. There were no Grade 4 or Grade 5 TRAEs.

Regulatory and Study Updates:

Turning Point also announced recent feedback received from the FDA and modifications the company is making to the study design that may accelerate the timelines to potential approval for repotrectinib. The FDA reiterated that the adequacy of the data to support approval will depend upon the observed ORR and the duration of response assessed in the context of available therapy in a risk-benefit analysis during NDA review.

These updates include:

 

   

Phase 2 cohort sample sizes to support potential approval may include Phase 1 patients treated at the recommended Phase 2 dose. The pooling of Phase 1 and Phase 2 data may shorten timelines to potential regulatory submission based on fewer patients from the Phase 2 portion of the study.

 

   

EXP-2 Cohort (ROS1 TKI-Pretreated with one prior TKI and one platinum-based regimen): The company plans to decrease the sample size from current target of 100 patients to 60 total patients with one formal interim analysis after approximately 30 patients. FDA provided guidance that 6 months of follow up may be sufficient to support approval.

 

   

EXP-4 Cohort (ROS1 TKI-Pretreated with one prior TKI and no prior chemotherapy): The company plans to increase the sample size to a target of 60 patients with one formal interim analysis after approximately 30 patients. Previously, EXP-4 was an exploratory cohort in this patient population. FDA provided guidance that 6 months of follow up may be sufficient to support approval.

 

   

EXP-5 and EXP-6 Cohorts (TRK TKI-Naïve and TKI-Pretreated): FDA provided guidance that 9 months and 6 months of follow up, respectively, from the last

 

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response may be sufficient to support approval. Previous guidance was 12 months for both patient cohorts.

Based on this FDA feedback and the subsequent sample size changes, the company is reviewing its timelines for when it expects the top-line interim analysis data sets will be achieved, and anticipates sharing those timelines as it gets closer to achieving full site activation in early 2021.

Webcast and Conference Call

Turning Point will host a webcast accompanied by a slide presentation to discuss the results at 8:00 a.m. EDT/5:00 a.m. PDT. Dr. Countouriotis will host the call, which will be accessible through the “Investors” section of tptherapeutics.com or by dialing (877) 388-2118 (in the United States) or (470) 495-9489 (outside the U.S.) using conference ID 5077833. A replay will be available through the “Investors” section of www.tptherapeutics.com.

About Turning Point Therapeutics Inc.

Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The company’s lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. The company’s pipeline of drug candidates also includes TPX-0022, targeting MET, CSF1R and SRC, which is being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET and SRC, which is being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor in IND-enabling studies. Turning Point’s next-generation kinase inhibitors are designed to bind to their targets with greater precision and affinity than existing therapies, with a novel, compact structure that has demonstrated an ability to potentially overcome treatment resistance common with other kinase inhibitors. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit www.tptherapeutics.com.

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Forward Looking Statements

Statements contained in this press release 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 efficacy, safety and therapeutic potential of repotrectinib, the results, conduct, progress and timing of the TRIDENT-1 clinical study, 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”

 

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and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Turning Point Therapeutics’ 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 Turning Point Therapeutics’ business in general, risks and uncertainties related to the impact of the COVID-19 pandemic to Turning Point’s business and the other risks described in Turning Point Therapeutics’ filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Turning Point Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

 

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