A 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 Gastro-Esophageal Junction (GEJ) Cancer

NCT04467515 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: CAMH2_1001
• Study Type: interventional
• Target: 13
• Locations: 2 countries
• Sites: 12

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.

Conditions

Advanced/Metastatic HER2-positive Breast, Gastric, Gastroesophageal Junction Cancer With Disease Progression Following Anti-HER2 Standard of Care Treatment

Outcome Measures

Primary Outcomes (2)

• Dose-limiting Toxicity (DLT) Rate Within the First Cycle

  Dose-limiting toxicity (DLT) rate of CAM-H2 assessed by toxicities occurring within the first cycle

  Within the first cycle of CAM-H2, up to 12 weeks

• Safety and Tolerability - Number of Treatment-emergent Adverse Events (TEAEs)

  Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  18 months

Secondary Outcomes (3)

• 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

Study Arms (1)

Dose Escalation and Expansion

EXPERIMENTAL

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.

Drug: CAM-H2

Interventions

CAM-H2 DRUG

All patients will receive at least 1 cycle of CAM-H2. Patients with CB may receive 4 cycles of CAM-H2, each cycle given as 2 IV administrations, 4 weeks apart.

Dose Escalation and Expansion

Eligibility Criteria

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

You may qualify if:

• 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;
• Neutrophil count \>1500 cells/mm3 without growth factor support (14 days after last PEGylated granulocyte colony stimulating factor or 7 days after regular granulocyte colony stimulating factor);
• Platelet count \>100,000 cells/mm3 without platelet transfusion in the last 2 weeks;
• Hemoglobin \>9.0 g/dL without blood transfusion in the last 2 weeks; and
• Adequate coagulation defined as an international normalized ratio (INR) ≤1.5 and activated partial thromboplastin time \<1.5 x the upper limit of the institutional normal range;
• Baseline left ventricular ejection fraction ≥ 50% as measured by echocardiography or multigated acquisition scan.

You may not qualify if:

• 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-H2.
• 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);
• Ongoing peripheral neuropathy of Grade \> 2 according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0;
• Severe and/or uncontrolled medical conditions or other conditions that could affect participation in the study such as:
• Symptomatic congestive heart failure of New York Heart Association Class III or IV;
• Unstable angina pectoris, symptomatic congestive heart failure, myocardial infarction within 6 months of start of study drug, serious uncontrolled cardiac arrhythmia, or any other clinically significant cardiac disease; or
• Liver disease, including cirrhosis and severe hepatic impairment;

Sponsors & Collaborators

• Precirix: lead

Study Sites (12)

City of Hope

Duarte, California, 91010, United States

Location

Stanford University Medical Center

Stanford, California, 94305, United States

Location

Georgetown University Medical Center

Washington D.C., District of Columbia, 20057, United States

Location

Loyola University Medical Center

Maywood, Illinois, 60153, United States

Location

University of Iowa

Iowa City, Iowa, 52242, United States

Location

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Advanced Molecular Imaging & Therapy

Glen Burnie, Maryland, 21061, United States

Location

Washington University School of Medicine in St. Louis

St Louis, Missouri, 63110, United States

Location

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, 10021, United States

Location

Princess Margaret Hospital

Toronto, Ontario, Canada

Location

Hospital Notre Dame du CHUM

Montreal, Quebec, Canada

Location

McGill University Faculty of Medicine - Royal Victoria Hospital

Montreal, Quebec, Canada

Location

Related Publications (1)

• D'Huyvetter M, Vos J, Caveliers V, Vaneycken I, Heemskerk J, Duhoux FP, Fontaine C, Vanhoeij M, Windhorst AD, Aa FV, Hendrikse NH, Eersels JLE, Everaert H, Gykiere P, Devoogdt N, Raes G, Lahoutte T, Keyaerts M. Phase I Trial of 131I-GMIB-Anti-HER2-VHH1, a New Promising Candidate for HER2-Targeted Radionuclide Therapy in Breast Cancer Patients. J Nucl Med. 2021 Aug 1;62(8):1097-1105. doi: 10.2967/jnumed.120.255679. Epub 2020 Dec 4.

  PMID: 33277400 DERIVED

Results Point of Contact

• Title: Jonathan Delara, Clinical Trial Manager
• Organization: Precirix

jonathan.delara@precirix.com

+1 (512) 589-2114

Study Officials

• Jonathan Delara

  Precirix

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

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

Model Details: This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to evaluate safety, tolerability, dosimetry, 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. The study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per cycle) of study drug, and a Long Term Follow Up Period. The study will be comprised of the following: * Dose Escalation Phase Followed by a Long Term Follow Up (LTFU) period * Dose Expansion Phase Followed by a LTFU period In the dose expansion phase of the study, the patients will be given the recommended dose for Phase 2 (RDP2) determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.

Study Record Dates

• First Submitted: June 10, 2020
• First Posted: July 13, 2020
• Study Start: September 14, 2021
• Primary Completion: December 11, 2023
• Study Completion: December 11, 2023
• Last Updated: May 6, 2025
• Results First Posted: May 6, 2025

Record last verified: 2025-04

Locations

CA (3); US (9)