A Study to Assess Safety, Tolerability and Imaging Characteristics of [68Ga]Ga-DPI-4452 and to Assess Safety, Tolerability, and Efficacy of [177Lu]Lu-DPI-4452 in Participants With Unresectable Locally Advanced or Metastatic Solid Tumors

Exclusion Criteria

• •Any major surgery within 12 weeks before enrolment.
• •Inability to stay in the scanner bed with the arms resting out of the thoracic and abdominal fields (i.e., arms alongside the body or raised arm position) for the duration of the scan.
• •Part A:
• •Has known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
• •Bladder outflow obstruction or unmanageable urinary incontinence.
• •Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, and/or stable Grade 2 sensory neuropathy, according to National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI-CTCAE\]).
• •Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of \[68Ga\]Ga-DPI-4452.
• •Previous Carbonic anhydrase (CA) IX-targeting treatment.
• •Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow, as judged by the Investigator.
• •Part B and Part C:
• •Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
• •Bladder outflow obstruction or unmanageable urinary incontinence.
• •Participants who have not had resolution of clinically significant toxic effects of prior systemic cancer therapy, surgery, active clinically significant cardiac disease, or radiotherapy to Grade ≤1 (except for laboratory parameters specified above, Grade 2 alopecia, or stable Grade 2 sensory neuropathy, according to NCI-CTCAE).
• •Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months prior to injection of \[68Ga\]Ga-DPI-4452.
• •Any previous CA IX-targeting treatment for non-oncological indication within 3 months prior to the \[177Lu\]Lu-DPI-4452 infusion; any previous CA IX-targeting treatment for any oncological indication.
• •Participants who received any systemic antineoplastic therapy for the underlying disease and/or other investigational agents within a period which is ≤5 half-lives or ≤4 weeks (whichever is shorter).
• •Inflammatory bowel disease (e.g Crohn's disease, ulcerative colitis, etc).
• •Part D:
• •Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
• •Any previous CA IX-targeting treatment within 3 months prior to the \[68Ga\]Ga-DPI-4452 injection.
• •Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of \[68Ga\]Ga-DPI-4452.
• •Malignant disease, other than that being treated in this study. Exceptions include the following: malignancies that were treated curatively and have not recurred within 2 years prior to screening; treated basal cell or localized squamous skin carcinomas, localized or low grade (e.g., Gleason 3+3 or 3+4 with low prostate specific antigen) prostate cancer, superficial (non-muscle invasive) urothelial cancer, localized thyroid gland microcarcinoma, other in-situ carcinoma, or other malignancy for which participants are not on active antineoplastic therapy.
• •Ongoing treatment with sulfonamides and/or coumarin derivatives (e.g., acenocoumarol, warfarin, phenprocoumon) within 2 weeks (or 5 half-lives, whichever is longer) prior to the \[68Ga\]Ga-DPI-4452 injection.
• •Part E:
• •Known hypersensitivity to the active substance, to any of the excipients of the DPI-4452, or to radiographic contrast agents.
• •Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of \[68Ga\]Ga-DPI-4452.
• •Any previous CA IX-targeting treatment within 3 months prior to \[68Ga\]Ga-DPI-4452 injection.
• •EBRT to more than 25% of the bone marrow, as judged by the Investigator.
• •Malignant disease, other than that being treated in this study. Exceptions include the following: malignancies that were treated curatively and have not recurred within 2 years prior to screening; treated basal cell or localized squamous skin carcinomas, localized or low grade (e.g., Gleason 3+3 or 3+4 with low prostate specific antigen) prostate cancer, superficial (non-muscle invasive) urothelial cancer, localized thyroid gland microcarcinoma, other in-situ carcinoma, or other malignancy for which participants are not on active antineoplastic therapy.