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

Phase 1

Completed

• Conditions: Adenocarcinoma; Stage IV; Non-small Cell Lung Cancer
• Interventions: Drug: Rigosertib; Drug: Nivolumab

• Registration Number: NCT04263090
• Lead Sponsor: Icahn School of Medicine at Mount Sinai

Brief 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.

Study Timeline

• Study First Submitted: 2020-02-05
• Study First Submitted QC: 2020-02-07
• Study First Posted: 2020-02-10
• Study Start: 2020-06-29
• Primary Completion: 2023-12-20
• Study Completion: 2023-12-20
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-08
• Last Update Posted: 2024-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 25

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Rigosertib + Nivolumab	Nivolumab	Rigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients
Rigosertib + Nivolumab	Rigosertib	Rigosertib + Nivolumab in metastatic KRAS+ lung adenocarcinoma patients

Primary Outcome Measures

Name	Time	Method
Maximal Tolerated Dose (MTD)	DLTs will be evaluated at the end of Cycle 1 (each cycle is 28 days)	MTD is defined as the highest dose for which at most 1 patient out of 6 experiences a dose-limiting toxicity (DLT)
Overall Response Rate (ORR)	2 years	ORR is defined as achieving an objective response of either complete response or partial response

Secondary Outcome Measures

Name	Time	Method
Progression Free Survival (PFS)	2 years	Phase 2: PFS is defined as the duration of time from start of treatment to the first occurrence of disease progression or death on study from any cause, whichever occurs earlier.
Overall Survival (OS) at MTD	2 years	Phase 2: OS at MTD is defined as the time from the first dose of study treatment to the date of death (whatever the cause).

Trial Locations

Locations (1)

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States