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NAUTILUS: OKI-179 Plus Binimetinib in Patients with Advanced Solid Tumors in the RAS Pathway (Phase 1b) and NRAS-mutated Melanoma (Phase 2)

Status
Completed
Cancer Type
Melanoma
Trial Phase
Phase I
Phase II
Eligibility
18 Years and older, Male and Female
Study Type
Treatment
NCT ID
NCT05340621
Protocol IDs
OKI-179-230 (primary)
NCI-2022-05165
Study Sponsor
OnKure, Inc.

Summary

The NAUTILUS study is a Phase 1b/2, multi-center, open-label study in which patients with
activating mutations in the RAS pathway (Phase 1b) and patients with NRAS-mutated
Melanoma (Phase 2) will be treated with a combination of oral OKI-179 combined with the
MEK inhibitor binimetinib.

Eligibility

  1. Phase 1b: Solid tumor refractory to standard treatment, for which no standard therapy is available, or if the patient refuses standard therapy
  2. Phase 1b: Tumor has an activating mutation in the RAS pathway confirmed by any local or central laboratory, including but not limited to RAS, BRAF, NF1, and GNAQ/11
  3. Phase 1b: Prior MEK inhibitor exposure may be allowed per Sponsor agreement
  4. Phase 2: Histologically confirmed, metastatic melanoma with a confirmed NRAS mutation determined by a validated NRAS mutation detection kit performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory
  5. Phase 2: Prior ICI treatment with a programmed cell death 1 (PD-1) or programmed death ligand 1 (PD-L1) checkpoint inhibitor, or ineligible for this type of therapy
  6. Phase 2: Consent for a tumor biopsy or can provide a recent archival tumor biopsy sample (within 2 years)
  7. Phase 2: At least 1 measurable lesion based on RECIST version 1.1
  8. Eastern Cooperative Oncology Group performance status of 0 or 1
  9. Normal organ and marrow function as defined below:
  10. Absolute neutrophil count = 1.5 × 109/L
  11. Platelets = 100,000/µL
  12. Hemoglobin = 9.0 g/dL (at least 1 week after packed red blood cells, if applicable)
  13. Total bilirubin within institutional ULN, unless patient has Gilbert's syndrome and has total bilirubin = 2.5 × institutional ULN
  14. Alanine aminotransferase and aspartate aminotransferase = 2.5 × institutional ULN or < 5 × institutional ULN in the presence of liver metastasis
  15. Serum creatinine < 1.5 × institutional ULN
  16. All prior treatment-related toxicities must have resolved to CTCAE version 5.0 criteria of Grade = 1, except for alopecia and ICI-related endocrinopathies managed with hormone replacement therapy (eg, thyroiditis/hypothyroidism, hypophysitis, diabetes mellitus type 1)
  17. Left ventricular ejection fraction (LVEF) = 50%
  18. Able to swallow and tolerate oral medications
  19. Life expectancy = 3 months

Treatment Sites in Georgia

Winship Cancer Institute of Emory University


1365 Clifton Road NE
Building C
Atlanta, GA 30322
winshipcancer.emory.edu

**Clinical trials are research studies that involve people. These studies test new ways to prevent, detect, diagnose, or treat diseases. People who take part in cancer clinical trials have an opportunity to contribute to scientists’ knowledge about cancer and to help in the development of improved cancer treatments. They also receive state-of-the-art care from cancer experts... Click here to learn more about clinical trials.