A Study of EP0031 (Lunbotinib) in Patients With Advanced RET-altered Malignancies

A Modular, Open-label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0031 in Patients With Advanced RET-altered Malignancies

The aim of this study is to assess the safety, side effects and effectiveness of EP0031 (Lunbotinib) in patients with advanced RET-altered non-small cell lung cancer (NSCLC) in monotherapy and in combination with standard of care (SOC) chemotherapy.

EP0031 is being investigated in this modular, interventional Phase I/II dose escalation and dose expansion study to investigate the optimal dose in adult patients with advanced RET-altered NSCLC. Currently there are no approved RET-targeted treatments for patients who progress on first-generation Selective RET Inhibitors (SRIs). However, it is proposed that EP0031 can overcome resistance mechanisms to first generation SRIs, as EP0031 is a potent and selective RET inhibitor with broad activity against common RET fusions and mutations. Phase I (dose escalation and optimization) has completed for this study and determined the Recommended Phase 2 Dose (RP2D). The study is now in Phase 2, assessing the safety, tolerability and efficacy of EP0031 given in combination with SOC chemotherapy in RET fusion positive NSCLC participants.

Inclusion Criteria:

Applicable to all participants:

1. Must be ≥18 years of age, with documented RET-altered NSCLC
2. Participants should be well informed and consented about alternative treatment options including approved RET-targeted therapies
3. ECOG performance status of 0 or 1 and life expectancy >3 months at screening
4. Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
5. Measurable disease defined by RECIST v1.1
6. Must have locally advanced or metastatic NSCLC with RET fusion who are eligible to receive platinum-based doublet chemotherapy.
7. First line patients: Must not have received a Selective RET inhibitor or chemotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior. Palliative radiotherapy for symptom management (eg, bone metastases) is permitted up to 2 weeks prior to treatment start.

Exclusion Criteria:

Participants with any of the following will not be included in the study:

1. Any known major driver gene alterations other than RET.
2. Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.
3. Active infection requiring systemic antibiotic, antifungal, or antiviral medication
4. Severe or uncontrolled medical condition or psychiatric condition
5. Chronic glomerulonephritis or renal transplant
6. Participants with active hepatitis B infection or active hepatitis C
7. Participants with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months
8. Receipt of any strong inhibitor or inducer of CYP3A4
9. Impaired hepatic or renal function, inadequate bone marrow reserve or organ function
10. Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade III-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months
11. Uncontrolled hypertension
12. Corneal ulceration or untreated keratitis at screening