NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGeorgetown University
About this trial
The goal of this clinical trial is to learn about the safety of NEROFE and doxorubicin and how well it works in patients with advanced/unresectable or metastatic solid KRAS-mutated and ST-positive solid tumors. The main question it aims to answer is to find the recommended dose and scheduled for the combination of NEROFE and doxorubicin. Participants will receive weekly doses of NEROFE and doxorubicin.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Advanced/unresectable or metastatic solid tumor with a pathogenic KRAS mutation via polymerase chain reaction (PCR), next-generation sequencing (NGS), or other standard test (blood-based DNA testing is allowed)
Presence of tumor ST2 expression via immunochemistry assay
Progression or intolerance to all standard therapies, patient may decline standard therapies and retain eligibility (patients must not have available curative options); patients must have been exposed to 2 or fewer lines of systemic therapy for advanced disease (these patients would decline any unused standard therapies which are still available)
Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
Disqualifiers
Age < 18 years
Prior exposure to anthracycline chemotherapy
Receiving any active anti-cancer therapy while on study treatment
Brain metastases unless they have been previously treated with surgery and/or radiation at least 4 weeks prior to C1D1 and have a baseline MRI that shows no evidence of active/progressing intracranial disease
Trial design
Design model
Sequential
Treatments tested in this trial
NEROFE
Drugweekly doses of NEROFE (48-288 mg/m2) (dose level 1: 96 mg/m2, dose level -1: 48 mg/m2, dose level 2: 192 mg/m2, dose level 3: 288 mg/m2), intravenously over 60 minutes
Doxorubicin
Drugweekly doses of 8 mg/m2 (fixed dose), intravenous push over 3 mins;
Treatment groups
24 Participants
are divided into 5 treatment groupsGroup A: Dose Level 1: NEROFE with doxorubicinExperimental treatment 2 interventions
Group B: Dose level -1: Nerofe with doxorubicinExperimental treatment 2 interventions
Group C: Dose level 2: Nerofe with doxorubicinExperimental treatment 2 interventions
Group D: Dose Level 3: Nerofe with doxorubicinExperimental treatment 2 interventions
Group E: Dose Level 4: Nerofe with doxorubicinExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Incidence of adverse events
Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors
Time frame
Cycle 1 Day 1 until 30 days following discontinuation of study drug, approximately 6 months.2
Incidence of Serious Adverse events
Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors
Time frame
From time of Consent until 30 days following discontinuation of study drug, approximately 6 months.3
Incidence of Adverse events meeting protocol defined dose limiting toxicities
Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors
Time frame
Cyce 1 Day 1 through 28 daysSecondary outcomes
1
Pharmacokinetic (PK): AUC (area under the curve) 0-24 hours
Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; AUC 0-24 hours calculated using the trapezoidal rule \[(Concentration at 0 hour + concentration at 24 hours) x 24\]/2
Time frame
24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)2
Pharmacokinetic: Cmax
Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; maximum 24 hour concentration
Time frame
24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)3
Pharmacokinetic: Cmin
Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; minimum 24 hours concentration
Time frame
24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)4
Pharmacokinetic: Tmax
Pharmacokinetics of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors; hour at which Cmax occurs
Time frame
24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Georgetown University
Lead sponsor
Immune System Key Ltd
Collaborator
Source ClinicalTrials.gov