ccRCC, Clear Cell Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma Metastatic, Kidney Cancer Metastatic, Kidney Cancers, RCC, Renal Cell Carcinoma, VHL-Associated Clear Cell Renal Cell Carcinoma, VHL-Associated Renal Cell Carcinoma
Conditions
Keywords
ccRCC, Renal Cell Carcinoma, Clear Cell Renal Cell Carcinoma, VHL, Kidney Cancer
Brief summary
The NEO-811-101 study is an open-label, first-in-human, Phase 1/2 dose escalation and expansion study testing NEO-811, an ARNT molecular glue degrader, in subjects with locally advanced or metastatic non-resectable clear cell renal cell carcinoma. The study will test NEO-811 initially as a monotherapy.
Interventions
DRUGNEO-811
NEO-811
Sponsors
Neomorph, Inc
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Subjects with locally advanced or metastatic non-resectable clear cell renal cell carcinoma (ccRCC). * Subjects must have progressed on or refused standard therapies. * Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0 or 1. * Estimated life expectancy, in the judgment of the Investigator, of at least 12 weeks. * Formalin-fixed paraffin-embedded (FFPE) tumor tissue, newly obtained or archival, is mandatory for enrollment to the study. * Measurable disease as defined by RECIST v1.1. * Adequate hematologic, hepatic, and renal function defined as: * Hemoglobin ≥10 g/dL, * Absolute neutrophil count ≥1000 cells/µL, * Platelet count ≥100,000/µL, * AST and ALT ≤2.5 × ULN, or AST and ALT ≤5 × ULN for subjects with liver metastases, * Total bilirubin ≤1.5 × ULN, * Estimated glomerular filtration rate (eGFR) ≥60 mL/min. * Subject can swallow oral medications and does not have a condition that could impair the oral bioavailability of the study drug. * Other inclusion criteria per protocol.
Exclusion criteria
* Non-clear cell predominant RCC histologic subtypes. * Leptomeningeal disease or symptomatic active CNS metastases with exceptions for asymptomatic treated CNS metastases per protocol. * Prior or concurrent malignancies with exceptions per protocol. * History of hepatitis B virus (HBV), hepatitis C virus (HCV), or HIV infection. * Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency and severity of treatment emergent adverse events (TEAEs) of NEO-811 as a single agent. | Start of Cycle 1 until at least 30 days following the last dose of the last treatment cycle (each treatment cycle is 21 days). | TEAEs will be assessed and severity assigned by using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 6.0. |
| Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of NEO-811 as a single agent. | Start of Cycle 1 until at least 30 days following the last dose of the last treatment cycle (each treatment cycle is 21 days). | The MTD and/or RP2D of NEO-811 as a single agent will be determined. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum observed plasma concentration (Cmax) of NEO-811. | Start of Cycle 1 until Day 1 of last treatment cycle (each treatment cycle is 21 days). | Maximum observed plasma concentration (Cmax) of NEO-811 will be determined. |
| Trough observed plasma concentration (Ctrough) of NEO-811. | Start of Cycle 1 until Day 1 of last treatment cycle (each treatment cycle is 21 days). | Trough observed plasma concentration (Ctrough) of NEO-811 will be determined. |
| Time to Cmax (Tmax) of NEO-811. | Start of Cycle 1 until Day 1 of last treatment cycle (each treatment cycle is 21 days). | Time to Cmax (Tmax) of NEO-811 will be determined. |
| Area under the concentration time curve (AUC) of NEO-811. | Start of Cycle 1 until Day 1 of last treatment cycle (each treatment cycle is 21 days). | Area under the concentration time curve (AUC) of NEO-811 will be determined. |
| Anti-tumor activity of NEO-811 as a single agent. | Start of Cycle 1 until documented disease progression or death, etc. (each treatment cycle is 21 days), estimated as 6-9 months. | Tumor response will be determined by RECISTv1.1. |
Countries
United States
Contacts
CONTACTSara Weymer
STUDY_DIRECTORKlaus Wagner, MD, PhD
Neomorph, Inc
Outcome results
None listed