NCT04263090

Rigosertib Plus Nivolumab for KRAS+ NSCLC Patients Who Progressed on First-Line Treatment

A Phase1/2a Study of Rigosertib Plus Nivolumab in Stage IV Lung Adenocarcinoma Patients With KRAS Mutation Who Progressed on First-Line Treatment

• Status: Completed
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 25 (actual)
• Sponsor: Icahn School of Medicine at Mount Sinai · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

A Phase1/2a Study of Rigosertib plus Nivolumab in Stage IV Lung Adenocarcinoma Patients with KRAS Mutation who Progressed on First-Line Treatment

Detailed description

This is an open-label, dose-escalating Phase I study followed by a Phase 2a dose-expansion phase to study the combination of Rigosertib and Nivolumab in metastatic Kirsten rat sarcoma positive (KRAS+) lung adenocarcinoma patients who have progressed on standard first line treatment. Study patients will have satisfied the inclusion/exclusion criteria enumerated in this protocol. The Phase I dose escalation plan will start with an accelerated titration design (ATD) using single patient cohorts until grade 2 toxicity is experienced. At that point, the ATD will be terminated and the dose escalation will enter a standard 3+3 design based on dose-limiting toxicities (DLT). The MTD (Phase 1 primary endpoint) is defined as the highest dose for which at most 1 patient out of 6 experiences a DLT. Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg in the morning (qAM), 280mg in the evening (qPM); dose D3: 560mg twice daily; taken by mouth for 21 consecutive days of the 28 day cycle), based on previous dose escalation studies in other malignancies, while Nivolumab dose will be fixed at the standard dose (240mg every 2 weeks, given intravenously). Once the MTD is determined, an additional planned 12 patients will be enrolled in the expansion phase to further study toxicity and to determine preliminary efficacy endpoints including ORR (phase 2a primary endpoint), PFS, and OS (secondary endpoints) of the combination.

Conditions

• Non-small Cell Lung Cancer
• Adenocarcinoma
• Stage IV

Interventions

Type	Name	Description
DRUG	Rigosertib	Rigosertib will be dosed twice a day for 21 consecutive days, followed by 7 days off treatment (each cycle duration: 28 days). Rigosertib escalation will occur with three dose levels (dose D1: 280mg twice daily; dose D2: 560mg qAM, 280mg qPM; dose D3: 560mg twice daily).
DRUG	Nivolumab	Nivolumab will be dosed once ever 2 weeks (twice per 28-day cycle; standard fixed dose of 240mg).

Timeline

• Start date: 2020-06-29
• Primary completion: 2023-12-20
• Completion: 2023-12-20
• First posted: 2020-02-10
• Last updated: 2024-05-09

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study