CARLSBAD, Calif.—Thermo Fisher Scientific and Eli Lilly and Company have initiated an agreement to develop a companion diagnostic, which will use the Oncomine Dx Target Test to identify patients with non-small cell lung cancer (NSCLC) or thyroid cancer who may benefit from treatment with Lilly's investigational therapy LOXO-292.
Per the terms of the agreement, Thermo Fisher will retain the rights to commercialize the resulting diagnostic in all markets, including the U.S., Europe and Japan. Once it has been validated, Thermo Fisher will submit a supplemental premarket approval application to the U.S. Food and Drug Administration.
"We are pleased to enter into this agreement with Lilly and leverage our Oncomine platform as a means to quickly identify cancer patients who may benefit from this breakthrough therapy, even in cases of limited sample availability,” said Mark Stevenson, executive vice president and chief operating officer of Thermo Fisher Scientific. “We are committed to working with our global pharmaceutical partners to help bring forth next-generation sequencing-based companion diagnostics and best-in-class therapies that can have a profound impact on treating cancer patients."
The test the partners will be developing will focus on patients whose tumors present with a rearranged during transfection (RET) alteration, a genetic variant found in roughly 2 percent of NSCLC cases, approximately 60 percent of medullary thyroid cancer (MTC) cases and nearly 20 percent of other thyroid cancers.
Lilly's LOXO-292 is a highly selective, potent oral inhibitor of RET. Alterations of the RET kinase can result in uncontrolled cell growth, and cancers driven by these kinds of alterations tend to be dependent on that singular pathway, which makes them susceptible to small-molecule inhibitors, according to a Thermo Fisher Scientific press release.
"One of the biggest barriers to realizing the full power of precision medicine in oncology is having access to high-quality testing, such as next-generation sequencing-based tests, that identify a broad range of clinically actionable alterations, can be performed locally and allow treating institutions to participate in this important step in the evolving treatment paradigm," Anne White, president of Lilly Oncology, commented in a statement. "With this agreement, we believe that more patients will gain access to high-quality tumor profiling, identifying those with RET alterations potentially suitable for LOXO-292 therapy, in addition to other alterations suitable for treatment with other therapies."
The same day, Lilly also announced data from its Phase 1/2 trial of LOXO-292. The LIBRETTO-001 trial is meant to support LOXO-292's registration for the treatment of RET fusion-positive NSCLC. In the registration dataset, comprised of the first 105 patients enrolled in the study with prior platinum-based chemotherapy, treatment with selpercatinib led to a 68-percent objective response rate (ORR). This group was heavily pretreated, with 55 percent having previously received anti-PD-1/PD-L1 antibody treatment and 48 percent having received treatment with at least one multikinase inhibitor, and ORR was similar regardless of prior treatment. In patients whose NSCLC had metastasized to the brain, LOXO-292 treatment resulted in a central nervous system ORR of 91 percent.
As of June 17, the data cut-off date, median duration of response (DOR) was 20.3 months, with progression-free survival (PFS) of 18.4 months. LOXO-292 was generally well tolerated, with only nine patients discontinuing the study due to treatment-related toxicity. The most common adverse events were dry mouth, diarrhea, hypertension, increased liver enzymes, fatigue, constipation, and headache.
In treatment-naïve patients with RET fusion-positive NSCLC, LOXO-292 treatment led to an ORR of 85 percent, and median DOR and PFS had not yet been reached given that most patients continued to respond to treatment or remain progression-free.
This study is the largest clinical trial of a RET inhibitor in patients with RET-altered cancers, according to Lilly. Lilly purchased Loxo Oncology in January of this year for approximately $8 billion, a transaction that netted the company LOXO-292, among other candidates in Loxo Oncology's pipeline.
"In this large cohort, selpercatinib's response rate, durability, robust CNS activity and safety show promise. Furthermore, this continues to confirm that RET fusions are clinically targetable alterations, placing them in the company of activating EGFR/ALK/ROS1 alterations. We are encouraged by these data as there is currently an unmet need to provide genomically tailored therapy to patients with RET fusion-positive NSCLCs," remarked Dr. Alexander Drilon, lead investigator, Memorial Sloan Kettering Cancer Center.
