IRB Study Number 19-697
Status Active, not recruiting
Phases Phase 1, Phase 2
Location Cleveland Clinic Main Campus
Institute Taussig Cancer Institute
- To provide access to LOXO-292 for patients with locally advanced or metastatic solid tumors with activating RET alterations (and other evidence of RET activation) who are 18 years of age or older
- To determine the safety profile and tolerability of LOXO-292
- Patients with a locally advanced or metastatic solid tumor with RET activation who:
- Are not eligible for an ongoing LOXO-292 clinical trial (e.g., for clinical, geographic or financial reasons), but are deemed appropriate candidates to receive LOXO-292 treatment by the Investigator and the Sponsor, or
- Have progressed on or are intolerant to standard therapy, or
- No standard therapy exists, or
- In the opinion of the Investigator, are not candidates for or who would be unlikely to derive significant clinical benefit from standard therapy
- Evidence of an activating RET gene alteration in tumor tissue from a laboratory with CLIA, International Organization for Standardization (ISO)/IEC, College of American Pathologists (CAP), or other similar certification (examples of RET activating mutations provided in Appendix B). A positive germline test for a RET mutation is acceptable for patients with MTC. In all cases, an anonymized/redacted Molecular Pathology Report or other report(s) describing tumor RET (and other) alteration analysis should be submitted to Sponsor or designee during/prior to eligibility. Patients identified as having a RET gene alteration of unknown significance or other evidence of RET activation (e.g., increased expression) may be considered for enrolment by the Sponsor if sufficient clinical rationale is provided and agreed upon. The Sponsor has final determination regarding eligibility based upon genomic findings. Blood-based testing which reveals an activating RET mutation should (whenever possible) be confirmed with tissue testing. If tumor tissue is unavailable for confirmatory testing, blood-based testing may be utilized for enrollment with Sponsor permission.
- Eighteen years of age or older at the time of consent
- Adequate hematologic, renal and hepatic function as defined in Section 6.1. Patients with values outside of the specified limits may be enrolled if approved by the Loxo Oncology medical monitor. In such cases, a modified starting dose and safety guided monitoring plan will be discussed with the Investigator for safe LOXO-292 exposure.
- Ability to provide consent.
- Provision of a signed informed consent prior to any protocol specific procedures. Patients already receiving LOXO-292 who enroll in this protocol must be reconsented and sign the consent form for this expanded access protocol.
- Patients who are deemed eligible by the Sponsor's medical monitor
- Willingness of men and women of reproductive potential to observe conventional and effective birth control for the duration of treatment and for 3 months following the last dose of study treatment; this may include barrier methods, such as condom or diaphragm with spermicidal gel.
- Major surgery within 14 days (2 weeks) prior to C1D1.
- Investigational agent (via clinical trial) or anticancer therapy within 5 half-lives or 2 weeks (whichever is shorter) prior to planned start of LOXO-292 unless considered by the Investigator to be safe, within the best interest of the patient and with prior Sponsor approval.
- Radiotherapy for palliation within 1 week of the first dose of study treatment, with the exception of patients receiving radiation to more than 30% of the bone marrow, which must be completed at least 4 weeks prior to the first dose of study treatment.
- CNS surgery or radiation surgery performed within 28 days of the first treatment, within 14 days if stereotactic radiosurgery [SRS]. In patients with symptomatic and/or progressive CNS disease or large CNS tumor burden or leptomeningeal disease, consideration should be given to local treatment (e.g., surgery, radiation) prior to initiation of LOXO-292 therapy if clinically indicated.
- Clinically significant active cardiovascular disease (including New York Heart Association [NYHA] class III/IV heart failure, stroke, severe valvular disease or uncontrolled hypertension defined as ≥ 140/80 sustained over multiple readings) or history of myocardial infarction within 6 months prior to C1D1; ongoing cardiomyopathy; or current prolongation of the QT interval corrected for heart rate using Fridericia's formula (QTcF) interval > 470 msec. Patients who meet this criteria may be enrolled (with a modified dosing strategy) if clinical rationale exists which is reviewed and agreed upon by the Sponsor.
- Active uncontrolled systemic bacterial, viral, or fungal infection or serious ongoing intercurrent illness, such as hypertension or diabetes, despite optimal treatment. Screening for chronic conditions is not required.
- Clinically significant active malabsorption syndrome or other condition likely to affect gastrointestinal absorption of the study drug.
- Pregnancy or lactation.
- Uncontrolled symptomatic hyperthyroidism or hypothyroidism (i.e., the patient required a modification to current thyroid medication within 7 days prior to the first dose).
- Uncontrolled symptomatic hypercalcemia or hypocalcemia.
- Current treatment with strong cytochrome P450 3A4 (CYP3A4) inhibitors or inducers (refer to Section 1.6.1).
- Known hypersensitivity to any of the components of the investigational agent, LOXO-292 or Ora-Sweet® SF and OraPlus®, for patients who will receive LOXO-292 suspension.
- Current treatment with PPIs. Note: Treatment with PPIs must be stopped 1 or more weeks prior to the first dose of LOXO-292.
- Any unresolved toxicities from prior therapy greater than the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study treatment with the exception of alopecia and Grade 2, prior platinum-therapy related neuropathy. If sufficient clinical rationale exists for treatment despite an unresolved toxicity of a higher Grade, this criterion may be waived with prior Sponsor approval.