Loxo Oncology Announces LOXO-292 Durability Update in Patients with RET Fusion-Positive Non-Small Cell Lung Cancer from LIBRETTO-001 at the IASLC 19th World Conference on Lung Cancer

- 25/26 (96%) Responding Patients Remain on Therapy, With Median Follow-Up of 9.5 Months -

STAMFORD, Conn., Sept. 25, 2018 (GLOBE NEWSWIRE) -- Loxo Oncology, Inc. (Nasdaq: LOXO), a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers, today announced updated interim clinical data for LOXO-292 from the global Phase 1/2 LIBRETTO-001 trial in patients with RET fusion-positive non-small cell lung cancer (NSCLC) who were initially included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting. In these 38 patients, approximately 3.5 months of additional patient follow-up were available, as were first follow-up scans for the eight patients most recently enrolled. Twenty-five of 26 (96%) responding patients remained on therapy, with median follow-up of 9.5 months. Inclusion of new restaging data for the most recently enrolled patients resulted in a 68% confirmed overall response rate in the presented subset. These data are being presented today at the 2018 IASLC 19th World Conference on Lung Cancer in Toronto (abstract 13922).

“I am pleased that the attendees of World Lung were able to see the activity of LOXO-292 in RET fusion-positive lung cancer,” said Geoffrey R. Oxnard, M.D., associate professor of medicine at Harvard Medical School and thoracic oncologist at Dana-Farber Cancer Institute. “It has been just a few months since ASCO, but the additional follow-up afforded by today’s data provide encouraging evidence that LOXO-292 can deliver durable responses in heavily pre-treated patients. It was additionally reassuring to see that that LOXO-292 appears to be well tolerated at the Phase 2 dose of 160 mg BID. With Breakthrough Therapy Designation in hand, LOXO-292 is moving rapidly through clinical development, so it is important for investigators and patients to pay attention to this emerging target and class of medicines.”

Trial Background

LIBRETTO-001 is a Phase 1/2 trial of LOXO-292 in advanced cancer patients who primarily have activating RET alterations. LIBRETTO-001 contains a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The primary endpoint of the Phase 1 is the determination of the maximum tolerated dose (MTD) or recommended dose for further study. Secondary endpoints include safety, overall response rate (by RECIST 1.1) and duration of response. Initial clinical data were first reported at the 2018 American Society of Clinical Oncology (ASCO) Annual Meeting.

Key Data Presented

The data presented today were based on a July 19, 2018 data cut-off date and included the 38 patients with RET fusion-positive NSCLC who were initially included in the LOXO-292 presentation at the 2018 ASCO Annual Meeting.

Patients were heavily pretreated, having received a median of three prior systemic treatment regimens. Thirty-nine percent had received both prior platinum-based chemotherapy and an anti-PD-1 or anti-PD-L1 therapy.

With 3.5 months of additional follow-up since the 2018 ASCO Annual Meeting presentation, LOXO-292 demonstrated encouraging, early evidence of durable activity, with 25 of 26 (96%) responding RET fusion-positive NSCLC patients remaining on therapy and 24 of 26 (92%) remaining in response (median follow-up of 8.5 months for all 38 patients; median follow-up of 9.5 months for responding patients). The longest responding patient on therapy was the first RET fusion-positive NSCLC patient enrolled, who had been on therapy for more than 14 months as of the data cut-off date.

The new data cutoff date allowed for the inclusion of first follow-up scans for eight patients who had not had any post-baseline response assessment as of the ASCO presentation. Of 38 patients with RET fusion-positive NSCLC, 26 demonstrated an objective response by RECIST 1.1 (all partial responses, including one patient with an unconfirmed partial response awaiting a confirmatory response assessment) and six additional patients demonstrated evidence of tumor regression (-3% to -29%). The overall response rate was 68% (26/38) (95% CI: 51%-83%) and the confirmed overall response rate was 68% (25/37) (95% CI: 50%-82%). Response assessments were performed by the local clinical trial sites.

Anti-tumor activity was observed regardless of RET fusion partner (including KIF5B) and prior treatment, including chemotherapy, immunotherapy and multikinase inhibitors. Four patients had RECIST target lesions in the central nervous system (CNS) and all four exhibited confirmed intracranial responses by RECIST 1.1 (one complete response, three partial responses).

Of the 82 patients in the safety analysis, most treatment-emergent adverse events were Grade 1 in severity and judged by the investigator as not related to LOXO-292. The treatment-emergent adverse events observed in ≥10% of patients, regardless of relationship to LOXO-292, were diarrhea (15% Grade 1, 7% Grade 2, 1% Grade 3), fatigue (9% Grade 1, 13% Grade 2, 0% ≥Grade 3), dry mouth (21% Grade 1, 0% ≥Grade 2), constipation (17% Grade 1, 2% Grade 2, 0% ≥Grade 3), hypomagnesemia (12% Grade 1, 1% Grade 2, 0% ≥Grade 3), cough (11% Grade 1, 1% Grade 2, 0% ≥Grade 3), headache (10% Grade 1, 1% Grade 2, 1% Grade 3) and nausea (9% Grade 1, 4% Grade 2, 0% ≥Grade 3). Four patients experienced adverse events ≥Grade 3 that were attributed to LOXO-292 (all Grade 3): tumor lysis syndrome, increased ALT/AST, diarrhea, and thrombocytopenia. All resolved with dose interruption. 160mg BID has been advanced as the Phase 2 dose, with dose exploration at 200mg BID ongoing to further characterize LOXO-292 safety and efficacy.

The presentation will be available online at https://ir.loxooncology.com/events-presentations.

About LOXO-292
LOXO-292 is an oral and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities in the rearranged during transfection (RET) kinase. RET fusions and mutations occur across multiple tumor types with varying frequency. LOXO-292 was designed to inhibit native RET signaling as well as anticipated acquired resistance mechanisms that could otherwise limit the activity of this therapeutic approach. LOXO-292 has been granted Breakthrough Therapy Designation by the U.S. FDA.

LOXO-292 is currently being studied in the global LIBRETTO-001 Phase 1/2 trial. For additional information about the LOXO-292 clinical trial, please refer to www.clinicaltrials.gov. Interested patients and physicians can contact the Loxo Oncology Physician and Patient RET Clinical Trial Hotline at 1-855-RET-4-292 or email clinicaltrials@loxooncology.com.

About RET-Altered Cancers
Genomic alterations in RET kinase, which include fusions and activating point mutations, lead to overactive RET signaling and uncontrolled cell growth. RET fusions have been identified in approximately 2% of non-small cell lung cancer, 10-20% of papillary and other thyroid cancers, and a subset of other cancers. Activating RET point mutations account for approximately 60% of medullary thyroid cancer (MTC). Both RET fusion cancers and RET-mutant MTC are primarily dependent on this single activated kinase for their proliferation and survival. This dependency, often referred to as “oncogene addiction,” renders such tumors highly susceptible to small molecule inhibitors targeting RET.

About Loxo Oncology
Loxo Oncology is a biopharmaceutical company developing highly selective medicines for patients with genomically defined cancers. Our pipeline focuses on cancers that are uniquely dependent on single gene abnormalities, such that a single drug has the potential to treat the cancer with dramatic effect. We believe that the most selective, purpose-built medicines have the highest probability of maximally inhibiting the intended target, with the intention of delivering best-in-class disease control and safety. Our management team seeks out experienced industry partners, world-class scientific advisors and innovative clinical-regulatory approaches to deliver new cancer therapies to patients as quickly and efficiently as possible. For more information, please visit the company's website at www.loxooncology.com.

Forward Looking Statements
This press release contains "forward-looking" statements within the meaning of the safe harbor provisions of the U.S. Private Securities Litigation Reform Act of 1995. Forward-looking statements can be identified by words such as: "anticipate," "intend," "plan," "goal," "seek," "believe," "project," "estimate," "expect," "strategy," "future," "likely," "may," "should," "will" and similar references to future periods. These statements are subject to numerous risks and uncertainties that could cause actual results to differ materially from what we expect. Examples of forward-looking statements include, among others, statements we make regarding the timing and success of our clinical trials, the potential therapeutic benefits and economic value of LOXO-292 or other product candidates, and timing of future filings. Further information on potential risk factors that could affect our business and its financial results are detailed in our most recent Quarterly Report on Form 10-Q, and other reports as filed from time to time with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, that may be made from time to time, whether as a result of new information, future developments or otherwise.

Contacts for Loxo Oncology, Inc.

Lauren Cohen
Director, Corporate Communications

Peter Rahmer
Endurance Advisors, LLC

Dan Budwick
1AB Media