A Phase 1/2, Open-Label, Single-Arm, Dose-Escalation and Dose-Expansion Study of the Safety, Tolerability, Pharmacokinetic, and Antitumor Activity of E-602 as a Single Agent and in Combination With Cemiplimab in Patients With Advanced Cancers
Brief SummaryThis is a Phase 1/2, first-in-human, open-label, dose escalation and dose-expansion study of E-602, administered alone and in combination with cemiplimab.
Detailed DescriptionThis study is being conducted to evaluate the safety, tolerability, PK, pharmacodynamics, and antitumor activity of E-602 in subjects with advanced cancers. Phase 1 of the study consists of dose escalation cohorts of E-602 as a monotherapy and in combination with cemiplimab. Dose escalation will utilize a modified 3+3 design. Any Phase 1 cohort may be backfilled, up to a total of 15 subjects to obtain additional safety, PK, and pharmacodynamic data at a particular dose level. Phase 1 will treat subjects with melanoma, ovarian cancer, non-small cell lung cancer (NSCLC), colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer. The safety and pharmacodynamic data will be evaluated to identify the maximum tolerated dose and recommended Phase 2 dose level for E-602 as monotherapy and in combination with cemiplimab. Phase 2 consists of dose-expansion disease cohorts in subjects with 3 types of advanced tumors: melanoma, NSCLC, and a third type to be determined (ovarian, colorectal, pancreatic, breast, gastric/EGJ, head and neck, or urothelial) based on available data. Phase 2 includes cohorts of E-602 as monotherapy and E-602 in combination with camiplimab. For each cohort in Phase 2, Simon's minimax 2-stage design will be used. The study is seeking to enroll a total of up to 273 subjects (up to 87 in Phase 1 and up to 186 in Phase 2). Subjects will participate in the study for about 16 months.
Inclusion and Exclusion Criteria
- Subjects with advanced or relapsed/refractory melanoma, ovarian cancer, NSCLC, colorectal cancer, pancreatic cancer, breast cancer, gastric/esophagogastric junction (EGJ) cancer, head and neck cancer, or urothelial cancer who have failed prior therapies. a. Subjects with melanoma, NSCLC, head and neck cancer, urothelial cancer, or mMSI-H or dMMR colorectal cancer must have had prior anti-PD-(L)1 pathway therapy and been deemed resistant (had progression on therapy or within 3 months of discontinuation of therapy).
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Subject has disease that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v.1.1.
- Adequate bone marrow, coagulation, renal function, and liver function as determined by laboratory tests Key
- For cohorts receiving E-602 and cemiplimab combination therapy:
- Prior moderate or severe hypersensitivity to cemiplimab or its formulation
- History of severe (≥ Grade 3) autoimmune complications or discontinuation due to toxicity following treatment with an anti-PD-(L)1 pathway therapy as a monotherapy, with the exception of asymptomatic Grade 3 elevations in lipase and/or amylase not associated with clinical manifestations of pancreatitis.
- Subject has an active autoimmune disease. The following are not exclusionary: vitiligo, type 1 diabetes, autoimmune endocrinopathies that are stable on hormone replacement therapy, or psoriasis that does not require systemic treatment.
- Previously received idelalisib.
- History of age-related macular degeneration (AMD).
- Recent surgery, treatment with another investigational agent, active infection, non-healing wound or uncontrolled bleeding/bleeding diathesis.
- Received a vaccine or prior radiotherapy within 14 days prior to Cycle 1 Day 1.
- Prior history of interstitial lung disease that required steroids or ≥ Grade 2 immune-related pneumonitis or has current non-infectious pneumonitis or interstitial lung disease. Subject has a history of ≥Grade 3 radiation pneumonitis, or Grade 2 radiation pneumonitis that has been active within the last 6 months.
- Untreated brain metastases.
- A known primary malignancy that is progressing or has required active treatment within the past 3 years.
- Subject is taking the equivalent of >10 mg/day oral prednisone or on systemic immunosuppressive therapy.
- Subject has had an allogeneic tissue or organ transplantation.
- History of thromboembolic event unless the event occurred > 6 months from Cycle 1 Day 1 and the subject is on anti-coagulation treatment.
Please contact the trial administrator to learn more about where you can participate in this trial. Please use the contact form on the right side.