A Multi-Center Open Label Dose Escalation and Dose Expansion Study to Evaluate Safety, Tolerability, Dosimetry, and Preliminary Efficacy of the HER2 Directed Radioligand CAM-H2 in Patients With Advanced/Metastatic HER2-Positive Breast, Gastric, and GEJ Cancer
Overview
- Phase
- Phase 1
- Intervention
- CAM-H2
- Conditions
- Advanced/Metastatic HER2-positive Breast, Gastric, Gastroesophageal Junction Cancer With Disease Progression Following Anti-HER2 Standard of Care Treatment
- Sponsor
- Precirix
- Enrollment
- 13
- Locations
- 12
- Primary Endpoint
- Safety and Tolerability - Number of Treatment-emergent Adverse Events (TEAEs)
- Status
- Terminated
- Last Updated
- 12 months ago
Overview
Brief Summary
This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to evaluate safety, tolerability, dosimetry, pharmacodynamics (PD), and efficacy of the targeted radionuclide therapeutic CAM-H2 in patients with progressive, advanced/metastatic HER2-positive breast, gastric, and GEJ cancer with disease progression following anti-HER2 standard of care treatment.
Detailed Description
The study duration for each phase will be up to 18 months. The study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per cycle) of study drug, and a 12-month Long-Term Follow-Up Period.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Informed consent form signed voluntarily before any study-related procedure is performed, indicating that the patient understands the purpose of, and procedures required for, the study and is willing to participate in the study;
- •Males and females ≥ 18 years of age at screening;
- •Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1;
- •HER2-positive locally advanced or metastatic breast cancer refractory to standard cancer treatment or HER2-positive locally advanced or metastatic gastric or GEJ cancer, refractory to standard cancer treatment.
- •Patients should have a minimum of 1 measurable lesion as defined by RECIST version 1.1 or a minimum of 1 measurable lesion as defined by RANO-BM within 4 weeks of the first dose of the study drug (Day 1). The lesion has to be a new lesion or progression of an existing lesion under the current therapy.
- •Any previous anti-HER2 treatment for advanced or metastatic disease is allowed. Patients with breast cancer should have had at least 2 previous systemic anticancer treatments for recurrent, locally advanced or metastatic cancer. Patients with gastric cancer or GEJ cancer should have had at least 1 previous anti-HER2 treatment.
- •Life expectancy \> 6 months;
- •Adequate organ function, determined by the following laboratory tests:
- •Adequate kidney function with an estimated glomerular filtration rate (eGFR) of \>59 mL/minute calculated using the Chronic Kidney Disease Epidemiology Collaboration equation;
- •Adequate hepatic function defined as an alanine aminotransferase (ALT) and aspartate aminotransferase (AST) \<2.5 x the upper limit of normal (ULN), or \<5 x ULN in patients with liver metastases, and total bilirubin \<2 x ULN;
Exclusion Criteria
- •Presence of frank leptomeningeal disease as a unique central nervous system feature or in association with brain parenchymal measurable lesion(s);
- •Symptomatic brain metastases; Note: Patients with asymptomatic treated and untreated brain metastases are eligible.
- •Previous local therapy for brain metastases, such as neurosurgery, stereotactic radiotherapy, or whole brain radiotherapy, administered within 6 weeks prior to administration of CAM-H2; Note: Previous therapy for brain metastases administered at least 6 weeks prior to CAM-H2 administration will be allowed.
- •For patients with brain metastases, any increase in corticosteroid dose during the 4 weeks prior to the first administration of CAM-H
- •Note: Corticosteroid treatment in a stable dose or decreasing dose for at least 4 weeks prior to the first administration of CAM-H2 is allowed.
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics or psychiatric illness/social situations that would limit compliance with study requirements;
- •Uncontrolled thyroid disease, defined as free triiodothyronine (T3) and free thyroxine (T4) \> 3 x ULN at screening;
- •Uncontrolled diabetes defined as a fasting serum glucose \> 2 x ULN or glycated hemoglobin levels \> 8.5% at screening;
- •Gastrointestinal (GI) tract disease resulting in an inability to take oral medication, malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (eg, Crohn's, ulcerative colitis);
- •Current active hepatic or biliary disease (exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease per Investigator assessment);
Arms & Interventions
Dose Escalation and Expansion
The dose escalation phase of the study will be an open label 3 + 3 design, where at least 3 patients are treated at each dose level. Dose escalation will be done via increases of the nominal activity of CAM-H2 in cohorts of 3 to 6 patients. In the dose expansion phase of the study, the patients will be given the RDP2 determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.
Intervention: CAM-H2
Outcomes
Primary Outcomes
Safety and Tolerability - Number of Treatment-emergent Adverse Events (TEAEs)
Time Frame: 18 months
Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
Dose-limiting Toxicity (DLT) Rate Within the First Cycle
Time Frame: Within the first cycle of CAM-H2, up to 12 weeks
Dose-limiting toxicity (DLT) rate of CAM-H2 assessed by toxicities occurring within the first cycle
Secondary Outcomes
- To Assess the Clinical Benefit (CB) of CAM-H2(18 months)
- Anti-drug Antibodies (ADAs) Development(18 months)
- Dosimetry Efficacy - Total Absorbed Dose(18 months)