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

NCT05661201 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: STUDY00005711
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Solid Tumor; KRAS Mutation-Related Tumors

Outcome Measures

Primary Outcomes (3)

• Incidence of adverse events

  Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors

  Cycle 1 Day 1 until 30 days following discontinuation of study drug, approximately 6 months.

• Incidence of Serious Adverse events

  Safety and tolerability of NEROFE and doxorubicin in patients with advanced KRAS-mutated and ST2-positive solid tumors

  From time of Consent until 30 days following discontinuation of study drug, approximately 6 months.

• 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

  Cyce 1 Day 1 through 28 days

Secondary Outcomes (10)

• Pharmacokinetic (PK): AUC (area under the curve) 0-24 hours

  24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)

• Pharmacokinetic: Cmax

  24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)

• Pharmacokinetic: Cmin

  24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)

• Pharmacokinetic: Tmax

  24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)

• Pharmacokinetic: t1/2

  24 hours, on Cycle 1 Day 1 and Cycle 2 Day 1 (each cycle is 28 days)

Study Arms (5)

Dose Level 1: NEROFE with doxorubicin

EXPERIMENTAL

weekly doses of NEROFE at 96 mg/m2, intravenously over 60 minutes

Drug: NEROFE; Drug: Doxorubicin

Dose level -1: Nerofe with doxorubicin

EXPERIMENTAL

weekly doses of NEROFE at 48 mg/m2, intravenously over 60 minutes

Drug: NEROFE; Drug: Doxorubicin

Dose level 2: Nerofe with doxorubicin

EXPERIMENTAL

weekly doses of NEROFE at 192 mg/m2, intravenously over 60 minutes

Drug: NEROFE; Drug: Doxorubicin

Dose Level 3: Nerofe with doxorubicin

EXPERIMENTAL

weekly doses of NEROFE at 288 mg/m2, intravenously over 120 minutes

Drug: NEROFE; Drug: Doxorubicin

Dose Level 4: Nerofe with doxorubicin

EXPERIMENTAL

twice weekly doses of NEROFE at 288 mg/m2, intravenously over 120 minutes

Drug: NEROFE; Drug: Doxorubicin

Interventions

NEROFE DRUG

weekly 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

Dose Level 1: NEROFE with doxorubicin; Dose Level 3: Nerofe with doxorubicin; Dose Level 4: Nerofe with doxorubicin; Dose level -1: Nerofe with doxorubicin; Dose level 2: Nerofe with doxorubicin

Doxorubicin DRUG

weekly doses of 8 mg/m2 (fixed dose), intravenous push over 3 mins;

Also known as: adriamycin

Dose Level 1: NEROFE with doxorubicin; Dose Level 3: Nerofe with doxorubicin; Dose Level 4: Nerofe with doxorubicin; Dose level -1: Nerofe with doxorubicin; Dose level 2: Nerofe with doxorubicin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Absolute neutrophil count ≥ 1500/mm3
• Creatinine clearance ≥ 50 mL/min/1.73 m2 using the formula: creatinine clearance = \[\[140 - age(yr)\]\*weight(kg)\]/\[72\*serum Cr(mg/dL)\] (multiply by 0.85 for women).
• AST and ALT ≤ 3 x the upper limit of normal of the institution's normal range and total bilirubin ≤ 1.5 x the upper limit of normal of the institution's normal range - if liver metastases are present, AST and ALT ≤ 5 x the upper limit of normal of the institution's normal range and total bilirubin ≤ 3 x the upper limit of normal of the institution's normal range unless there is persistent nausea, vomiting, right upper quadrant pain, fever, rash, or eosinophilia
• Partial Thromboplastin Time (PTT) must be ≤ 1.5 × upper limit of normal of institution's normal range and INR (International Normalized Ratio) \< 1.5. Subjects on anticoagulation (such as warfarin) will be permitted to enroll as long as the INR is in the acceptable therapeutic range as determined by the investigator
• Patients must have fully recovered from all effects of surgery. Patients must have had at least two weeks after minor surgery and four weeks after major surgery before starting therapy. Minor procedures requiring "twilight" sedation such as endoscopies or mediport placement may only require a 24-hour waiting period, but this must be discussed with an investigator
• Women of childbearing potential must have a negative serum pregnancy test within 14 days prior to initiation of treatment and/or postmenopausal women must be amenorrheic for at least 12 months to be considered of non-childbearing potential
• Patient is capable of understanding and complying with parameters as outlined in the protocol and able to sign and date the informed consent, approved by the Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures
• Have measurable disease by RECIST v. 1.1
• Have disease amenable to serial core tumor biopsies
• Suitable, stable venous access to allow for all study-related blood sampling (a central line such as a portacath (e.g. Medi-Port) or PICC is highly encouraged)

You may not qualify if:

• 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

Sponsors & Collaborators

• Georgetown University: lead
• Immune System Key Ltd: collaborator

Study Sites (1)

Georgetown Lombardi Comprehensive Cancer Center

Washington D.C., District of Columbia, 20007, United States

RECRUITING

MeSH Terms

Interventions

tumor-cells apoptosis factor, human; Doxorubicin

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Benjamin Weinberg, MD

  Georgetown University

  STUDY CHAIR

Central Study Contacts

Emmy Mckissick

CONTACT

(202) 687-1104; mm5350@georgetown.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 28, 2022
• First Posted: December 22, 2022
• Study Start: April 12, 2023
• Primary Completion (Estimated): January 1, 2027
• Study Completion (Estimated): January 1, 2027
• Last Updated: March 6, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)