Phase 1b/2 Study of Nadunolimab with Gemcitabine and Carboplatin in Advanced Triple Negative Breast Cancer Patients
- Trial ID
- 2024-512052-38-00
- Protocol
- CAN04CLIN005
- Sponsor
- Cantargia AB
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **safety** and **tolerability** of **nadunolimab** in combination with **gemcitabine** and **carboplatin** in patients with advanced **triple negative breast cancer** during Phase Ib. This phase aims to establish the maximum tolerated dose (MTD) of the combination therapy. In Phase II, the study seeks to assess the efficacy of the combination treatment by determining the objective response rate (ORR) according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1, as evaluated by investigators. These objectives are clinically relevant as they aim to determine the potential of nadunolimab, in combination with established chemotherapeutic agents, to improve treatment outcomes in a challenging cancer subtype with limited therapeutic options.
Participants
The clinical trial involves participants diagnosed with **advanced triple negative breast cancer**. The study population includes both female and male patients aged 18 years and older. Participants are required to have a histologically confirmed diagnosis of triple negative breast cancer that is either locally recurrent, inoperable, or metastatic. The trial does not exclude patients based on their BRCA1/2 mutational status. Participants must have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. The trial population was selected based on their eligibility to receive gemcitabine and carboplatin as a line of therapy, with no more than one previous line of systemic therapy for advanced disease. Adequate organ and bone marrow function is required, and participants must have at least one measurable lesion suitable for repeated assessment. The sponsor has not provided information regarding the total number of participants in the study.
Plans and Procedures
The clinical trial is designed as a **randomized**, non-comparative, open-label, phase 1b/2 study to evaluate the combination of **nadunolimab** with **gemcitabine hydrochloride** and **carboplatin** in patients with advanced **triple negative breast cancer**. The primary objective in Phase Ib is to assess the safety and tolerability of the combination and to establish the maximum tolerated dose (MTD). In Phase II, the efficacy of the combination will be evaluated in terms of overall response rate (ORR) according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1.
The trial is expected to run until August 31, 2026, with recruitment having started on January 11, 2022. Participants will be involved in the study for the duration of their treatment cycles, with the possibility of early termination if they experience dose-limiting toxicity or if their disease progresses. The study includes several key visits: an initial screening visit to confirm eligibility, regular follow-up visits to monitor safety and efficacy, and an end-of-study visit to assess final outcomes.
Participants will be required to attend scheduled visits, adhere to the treatment plan, and undergo laboratory tests and other study procedures. The inclusion criteria specify that participants must be adults aged 18 or older with histologically confirmed triple negative breast cancer that is either locally recurrent, inoperable, or metastatic. They must have documented progressive disease and be eligible to receive gemcitabine and carboplatin as the next line of therapy. Adequate organ and bone marrow function is also required, along with a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) scale.
Participants may be excluded from the study if they do not meet the inclusion criteria or if they experience significant adverse effects that necessitate withdrawal. The trial aims to provide valuable data on the safety and efficacy of the treatment combination, contributing to the development of new therapeutic options for patients with advanced triple negative breast cancer.
Treatment
The clinical trial involves the administration of three primary substances: **Nadunolimab**, **Carboplatin**, and **Gemcitabine Hydrochloride**. Nadunolimab, also known as CAN04 or Nidanilimab, is a protein-based investigational drug provided in a **solution for infusion** form. It is administered via **intravenous administration**. The dosing schedule and frequency are determined based on the phase of the trial, with compliance monitored through standard clinical trial procedures.
**Carboplatin** is a chemotherapeutic agent classified under the ATC code L01XA02. It is provided in a pharmaceutical form designated as PHF00230MIG and is administered through **intravenous infusion**. The dosage and frequency are aligned with the trial protocol, ensuring adherence to safety and efficacy standards. Participant compliance is monitored through regular assessments and documentation.
**Gemcitabine Hydrochloride**, a nucleoside analog chemotherapeutic agent, is also provided in the PHF00230MIG form. It is administered via **intravenous infusion**. The administration schedule is consistent with the trial's design, and participant adherence is tracked through systematic monitoring. This agent is identified by the ATC code L01BC05, and its administration is carefully coordinated with the other investigational treatments to evaluate the combined therapeutic effect.
Throughout the trial, the combination of Nadunolimab with Gemcitabine and Carboplatin is evaluated for safety, tolerability, and efficacy in patients with advanced triple-negative breast cancer. The trial is structured to assess the maximum tolerated dose (MTD) and overall response rate (ORR) according to RECIST version 1.1 criteria. Compliance with dosing schedules and administration protocols is rigorously monitored to ensure the integrity of the trial data.
Efficacy
The efficacy of the investigational treatment in this clinical trial will be assessed during Phase II by evaluating the **Objective Response Rate (ORR)**. The ORR is defined as the rate of Complete Response (CR) plus Partial Response (PR) according to the Response Evaluation Criteria for Solid Tumors (RECIST) version 1.1. This assessment will be conducted on patients who receive at least one dose of the treatment and have measurable disease. The results will be compared against the ORR in the control arm to determine the efficacy of the combination of nadunolimab with gemcitabine and carboplatin in patients with advanced triple-negative breast cancer.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed informed consent form before conducting any specific procedure for the study.
- Female or male BC patients of ≥ 18 years of age.
- Histologically confirmed TNBC that is either locally recurrent, inoperable and cannot be treated with curative intent or is metastatic: a. Documented Hormone Receptor (HR) negative BC based on local laboratory determination on the most recent tumor biopsy; b. Documented Human Epidermal Growth Factor Receptor 2 (HER2) negative BC based on local laboratory determination on the most recent tumor biopsy; c. Patients are eligible for the study irrespectively of BRCA1/2 mutational status.
- Patients should be eligible to receive gemcitabine and carboplatin as the following line of therapy. No more than 1 previous line of systemic therapy for the advanced disease is allowed.
- Documented progressive disease (i.e. biopsy sample, pathology or imaging report) from the last treatment.
- Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 1.
- Patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT scan, MRI, plan X-ray or physical examination.
- Adequate organ and bone marrow function defined as follows: a. ANC ≥ 1.500/mm3 (1.5x109/L), without previous G-CSF within 2 weeks prior to the study treatment; b. Platelets ≥ 100.000/mm3 (100x109/L), without previous transfusion within 2 weeks prior to the study treatment; c. Hemoglobin ≥ 9 g/dL (90 g/L), without previous transfusion within 28 days before starting with the study treatment; d. Serum creatinine ≤ 1.5 x ULN or estimated creatinine clearance ≥ 60 mL/min as calculated using the Cockcroft-Gault formula; e. Total serum bilirubin ≤ 1.5 x ULN (≤ 3.0 x ULN if Gilbert´s disease); f. AST and/or ALT ≤ 3.0 x ULN (≤ 5.0 x ULN if liver metastases present); g. Alkaline phosphatase ≤ 2.5 x ULN (≤ 5.0 x ULN if bone or liver metastases present).
- Resolution of all acute toxic effects of prior anti-cancer therapy or surgical procedures to NCI CTCAE v5.0 Grade ≤ 1
- Patients testing positive for human immunodeficiency virus (HIV) are NOT excluded from this study, but HIV-positive patients must meet ALL the following criteria: a. Have CD4+ T-cell (CD4+) counts ≥ 350 cells/µL; b. Have not had an opportunistic infection within the past 12 months. Patients on prophylactic antimicrobials can be included in the study; c. Should be on stable antiretroviral therapy for at least 4 weeks; d. Have an HIV viral load less than 400 copies/mL prior to enrolment.
- Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures.
- Negative serum pregnancy test within 7 days prior to enrolment for premenopausal women, and for women who have experienced menopause onset < 12 month prior to first dose of therapy. • For premenopausal women: agreement to remain abstinent or use single or combined non-hormonal contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 7 months after the last dose of study treatment. • For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and to refrain from donating sperm during the same period, as defined below with female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for at least 6 months after the last dose of carboplatin/gemcitabine to avoid exposing the embryo.
Exclusion Criteria
- Patient has received extended field radiotherapy ≤ 4 weeks before the start of treatment (≤ 2 weeks for limited field radiation for palliation), and who has not recovered to ≤ Grade 1, according to NCI CTCAE v5.0, from related AEs of such therapy (except for alopecia).
- Treatment with systemic anticancer treatments, investigational products, or major surgery within 4 weeks before the first dose of study drug or 5 half-lives, whichever is shorter.
- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina, known left ventricular ejection fraction (LVEF) < 50%.
- Presence of an abnormal ECG that is clinically significant in the investigator’s opinion.
- Patients with uncontrolled brain metastases.
- Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for > 2 weeks prior to enrolment.
- Severe (Grade 3) infection requiring oral or IV antibiotics within 4 weeks prior to enrolment.
- Positive hepatitis B surface antigen (HBsAg) test at screening. Total hepatitis B core antibody (HBcAb) test at screening must be negative.
- Positive hepatitis C virus (HCV) antibody test at screening: if positive, HCV antibody test followed by a negative HCV RNA test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test.
- Pregnant or lactating or intending to become pregnant during or within 6 months after the last dose of study treatment.
- Known hypersensitivity or allergy to any component of the nadunolimab, carboplatin or gemcitabine drug formulations, and known hypersensitivity to platinum-containing compounds.
- Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications.
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Spain | Not Recruiting | 11 Jan 2022 | 117 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
CAN04 | Test | SOLUTION FOR INFUSION | INTRAVENOUS ADMINISTRATION | — | — | PRD4950545 |
CARBOPLATIN | Other | PHF00230MIG | INTRAVENOUS INFUSION | — | — | SCP10337134 |
GEMCITABINE | Other | PHF00230MIG | INTRAVENIOUS INFUSION | — | — | SCP1128788 |