NEROFE and Doxorubicin in KRAS-mutated ST2-positive Solid Tumors

Eligibility Criteria

• * 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)
• * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2
• * Laboratory
• * 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
• * Anti-tumor therapy within 3 weeks of C1D1 (defined as, but not limited to, cytotoxic chemotherapy, immunotherapy, biological therapy, radiotherapy, and investigational agents), the "wash-out period"
• * Concurrent severe illness or uncontrolled medical condition that, in the investigator's judgement, would cause unacceptable safety risks
• * Women who are pregnant or breastfeeding
• * Concurrent use of an aromatase inhibitor
• * Psychiatric illness or social situation that would limit compliance with study requirements
• * Concurrent malignancy or malignancy within 2 years prior to starting study drug, with the exception of adequately treated, basal or squamous cell carcinoma, non-melanomatous skin cancer or curatively resected cervical cancer, or a malignancy that the investigator deems has been definitively treated (e.g. early stage prostate cancer)
• * Active hepatitis B, C, or HIV (patients with hepatitis C infection are eligible if they have an undetectable viral load following definitive treatment, patients with HIV are eligible if they have an undetectable viral load and a CD4 count above 500 cells/mm3)
• * Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
• * History of acute coronary syndromes (including myocardial infarction, unstable angina, coronary artery bypass grafting, coronary angioplasty, or stenting) or symptomatic pericarditis within 6 months prior to screening
• * History of documented congestive heart failure (New York Heart Association functional classification III-IV)
• * Documented cardiomyopathy
• * Left Ventricular Ejection Fraction (LVEF) \<50% as determined by Multiple Gated acquisition (MUGA) scan or echocardiogram (ECHO) at screening
• * Clinically significant cardiac arrhythmias (e.g. ventricular tachycardia), complete left bundle branch block, high-grade AV block (e.g. bifascicular block, Mobitz type II and third-degree AV block)
• * QTcF (using Fridericia's correction) of \> 480 msec
• * Long QT syndrome or family history of idiopathic sudden death or congenital long QT syndrome, or any of the following:
• 1. Risk factors for Torsades de Pointe (TdP) including uncorrected hypokalemia or hypomagnesemia, history of cardiac failure, or history of clinically significant/symptomatic bradycardia.
• 2. Concomitant use of medication(s) with a known risk to prolong the QT interval and/or known to cause Torsades de Pointe that cannot be discontinued (within 5 half-lives or 7 days prior to starting study drug) or replaced by safe alternative medication
• 3. Inability to determine the QT interval on screening (QTcF, using Fridericia's correction)
• * Systolic blood pressure (SBP) \>160 mmHg or \<90 mmHg at screening