Study of [177Lu]Lu-DWJ155 and [68Ga]Ga-DWJ155 in Patients With Solid Tumors

A Phase I Open-label, Multi-center Study to Evaluate the Safety, Tolerability, Dosimetry, and Preliminary Activity of [177Lu]Lu-DWJ155 and Safety and Imaging Properties of [68Ga]Ga-DWJ155 in Patients With Solid Tumors

The purpose of this phase I study is to evaluate the safety, tolerability, dosimetry, and preliminary anti-tumor activity of [177Lu]Lu-DWJ155 and the safety and imaging properties of [68Ga]Ga-DWJ155 in patients with histologically or cytologically confirmed advanced HER2+, HR+/HER2-negative, or triple negative breast cancer (TNBC), non-small cell lung cancer (NSCLC), HER2-3+ or 2+ (ISH positive or negative) gastric/gastroesophageal junction (GEJ) cancer, and bladder cancer.

The study will be done in two parts. The first part is called "escalation" and the second part is called "expansion". In both parts of the study, patients will initially be imaged with a [68Ga]Ga-DWJ155 positron emission tomography (PET)/computed tomography (CT) or PET/magnetic resonance imaging (MRI) scan. In the escalation part, different doses of [177Lu]Lu-DWJ155 will then be tested to identify recommended dose(s) (RD(s)) for further evaluation. The expansion part of the study will examine the safety and preliminary efficacy of [177Lu]Lu-DWJ155 at the RD(s) determined during the escalation part.

In both parts, there will be a safety follow-up period after the last [177Lu]Lu-DWJ155 administration.

Inclusion Criteria:

• Male or female patients age ≥ 18 years.

• Patients with one of the following histologically or cytologically confirmed and documented malignancies who have progressed on or been intolerant to standard of care therapy, and are not considered appropriate for any standard therapy with proven benefit, in the investigator's judgment:

• Dose Escalation:

  • Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
  • Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
  • Advanced NSCLC without actionable genetic alterations (AGAs) with disease progression after prior therapy in the advanced setting
  • Advanced NSCLC with AGAs who have received prior treatment
  • Measurable disease as determined by RECIST version 1.1.

• Dose Expansion:

  • Advanced HER2+ breast cancer with disease progression after at least two prior lines of systemic therapy in the advanced setting
  • Advanced HR+/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
  • Advanced HR+/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
  • Advanced HR-/HER2-low breast cancer with disease progression after prior therapy in the advanced setting
  • Advanced HR-/HER2 0 breast cancer with disease progression after prior therapy in the advanced setting
  • Advanced NSCLC with AGAs, who have received prior treatment
  • Advanced NSCLC without known AGAs who have received prior treatment.
  • Advanced gastric/GEJ cancer with HER2 IHC 3+ or 2+ (ISH + or -), following disease progression after prior therapy in the advanced setting
  • Advanced bladder cancer following disease progression after prior therapy in the advanced setting
  • Measurable disease as determined by RECIST version 1.1.

Exclusion Criteria:

• Out-of-range laboratory values defined as:

  • Creatinine clearance < 60 mL/min (calculated using CKD-EPI 2021 formula, or measured)
  • Total bilirubin > 1.5 x ULN (except for patients with Gilbert's syndrome who are excluded if total bilirubin >3.0 x ULN) or direct bilirubin > 1.5 x ULN
  • Alanine aminotransferase (ALT) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if ALT > 5 x ULN
  • Aspartate aminotransferase (AST) > 3 x ULN, except for patients with tumor involvement of the liver who are excluded if AST > 5 x ULN
  • Lipase > 1.5 x ULN
  • Absolute neutrophil count (ANC) < 1.5 x 109/L
  • Hemoglobin < 9 g/dL
  • Platelet count < 100 x 109/L

• Initiation of hematopoietic colony stimulating factors, thrombopoietin mimetics, or erythroid stimulating agents initiated ≤ 2 weeks prior to imaging agent administration.

• Use of transfusion support ≤4 weeks prior to imaging agent administration.

• Impaired cardiac function or clinically significant cardiac disease.

• Unmanageable urinary tract obstruction or urinary incontinence.

• Any serious uncontrolled infection (acute or chronic).

• Pregnant or breastfeeding women.

• Treatment with any of the following anti-cancer therapies prior to imaging agent administration within the stated timeframes:

  • Prior treatment with any therapeutic radiopharmaceutical
  • < 10 half-lives for any imaging radiopharmaceutical
  • ≤ 4 weeks for external beam radiation therapy (EBRT) or brachytherapy
  • ≤ 6 months for lung-directed external beam radiotherapy

• Patients with non-tumor uptake of [68Ga]Ga-DWJ155 in tissues or organs that, in the opinion of the investigator, increases the risk associated with [177Lu]Lu-DWJ155 treatment.

Other protocol-defined inclusion/exclusion criteria may apply.