68GA-DPI-4452 for Clear cell renal cell carcinoma | Pancreatic ductal adenocarcinoma | Colorectal cancer | Urothelial carcinoma | Indeterminate renal mass | Head and neck cancer | Triple Negative breast cancer | Squamous non-small cell lung cancer

Inclusion criteria

• {"criterion_text":"- 1_Part A: Histologically or cytologically confirmed, unresectable locally advanced or metastatic solid tumors of: -ccRCC; - PDAC; - CRC.\n- 3_Part A: Patient ECOG performance status 0-2\n- 4_Part A: Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at Screening\n- 5_Part A: Adequate blood counts: - Hemoglobin ≥8 g/dL - Absolute neutrophil count (ANC) ≥1.0 × 109/L - Platelets ≥50 × 109/L\n- 6_Part A: Adequate hepatic function: - Aspartate or alanine aminotransferase or alkaline phosphatase (AST, ALT, ALP) ≤ 3.0 × upper limit of normal (ULN) (≤ 5.0 ×ULN if patient has liver metastases) - Bilirubin ≤ 1.5 × ULN (a. up to 2.0 × ULN is allowed if the direct bilirubin level is normal, and the elevation is limited to indirect bilirubin b. Up to 5.0 x ULN in case of Gilbert’s Syndrome)\n- 7_Part A: Adequate renal function: - For PDAC and CRC patients: estimated glomerular filtration rate (eGFR) >50 mL/min/1.73 m² (as determined by the Chronic Kidney Disease - Epidemiology Collaboration - creatinine [CKD-EPIcr] formula) - For ccRCC patients: eGFR > 40 mL/min/1.73 m²(CKD-EPIcr)\n- 8_Parts B, C: Histologically or cytologically confirmed progressive, unresectable locally advanced or metastatic solid tumors of: -ccRCC; - PDAC; -UC.\n- 9_Parts B, C: Measurable disease per RECIST v1.1\n- 17_PART B, C: Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging (CT/MRI) documented after or during the last anticancer therapy and within 64 weeks preceding the planned [177Lu]Lu-DPI-4452 [68Ga]Ga-DPI-4452 administration (for scan dated more than 6 weeks prior to C1D1, the Sponsor should be contacted to assess conventional imaging suitability)\n- 18_Part B and C: ≥75% of the lesions detected by standard imaging (CT scan, MRI) assessed locally by the Investigator (for Part B) or assessed by central reading (Part C) must be positive by [68Ga]GaDPI-4452 PET. Upon agreement between the Sponsor and Investigator, patients with PDAC and patients with UC with <75% lesion positivity may be eligible if their primary tumor or their biggest tumor lesion as detected by standard imaging (CT scan, MRI) is positive by [68 Ga]Ga- DPI-4452 PET as per local assessment.\n- 19_Part B and C: Patients with known central nervous system (CNS) metastasies will be eligible if they are clinically stable, and asymptomatic. Patients must have completed primary CNS therapy more than 4 weeks before treatment start (such as whole brain radiotherapy, stereotactic radiosurgery, or complete surgical resection). Low doses of steroids for the purposes of maintaining neurological integrity (not exceeding of prednisolone 10 mg/day or equivalent) are allowed. For patients with CNS metastasies (or a history of CNS metastasies), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast).\n- 10_Parts B, C: Patient ECOG performance status 0-1\n- 20_Part D: Patients with Imaging evidence of a single indeterminate renal mass of ≤ 7 cm in largest diameter (tumor stage cT1) on any conventional diagnostic imaging technique, suspicious for ccRCC and planned for total or partial nephrectomy, or interventional diagnostic (cystoscopy and retrograde pyelography or biopsy) within 90 days from planned [68Ga]Ga-DPI-4452 administration;\n- 21_Part D, E: Adequate renal function: Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 (as determined by the Chronic Kidney Disease – Epidemiology Collaboration - creatinine [CKDEPIcr] formula)\n- 22_Part A, B, C, D, E: WOCBP (defined as sexually mature women who have not undergone bilateral tubal ligation, bilateral oophorectomy or hysterectomy or who have not been postmenopausal) must have a negative serum pregnancy test at screening and must not be breastfeeding. Additionally, they must agree to use highly effective methods of contraception from informed consent form (ICF) signature for 6 months after the [68Ga]Ga-DPI-4452 injection (all cohorts) and for 8 months after the last 177 [Lu]Lu-DPI-4452 infusion (part B and C only). Sexual abstinence is acceptable only if it is consistent with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of birth control : •A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A FSH level at screening (>40 IU/L) in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, women will be considered of childbearing potential • Permanently sterile. Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and bilateral oophorectomy at least 6 months prior to first dosing or documented congenital sterility • Highly effective methods of contraception include combined (estrogen- and progestogen-containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion/ligation procedures, vasectomized partner, and sexual abstinence during the entire study duration if in adequation with the patient usual lifestyle. Periodic abstinence (e.g., calendar, symptothermal, post-ovulation methods) and withdrawal are not considered as a highly effective method and are not acceptable\n- 23_Part A, B, C, D, E: Sexually active men must agree to use a condom during intercourse, refrain from fathering a child during treatment period, and donate sperm for 3 months after the [68Ga]GaDPI-4452 injection (all cohorts) and for 5 months after the last [177Lu]Lu-DPI-4452 infusion (part B and C only) Female partners of childbearing potential must agree to practice sexual abstinence or be under highly effective birth control method for the above mentioned duration.\n- Part E: Regardless of lines of treatment, patients with histologically or cytologically confirmed progressive, unresectable locally advanced or metastatic solid tumors of • UC, including MIBC • HNSCC • TNBC • Squamous NSCLC • Any other indication with confirmed CA IX expression, excluding ccRCC, PDAC and CRC, upon Sponsor agreement\n- 25_Part E: Presence of at least 1 non-irradiated tumor lesion detected at conventional imaging (CT/MRI) documented within 4 weeks prior to the [68Ga]Ga-DPI-4452 administration (for scans dated more than 4 weeks prior to D1, the Sponsor should be contacted to assess conventional imaging suitability)\n- 11_Parts B, C: Life expectancy >6 months\n- 12_Parts B, C: Adequate bone marrow reserve and organ function as demonstrated by complete blood count, and biochemistry in blood and urine at Screening\n- 13_Parts B, C: Adequate blood counts: - Hemoglobin ≥9 g/dL - ANC ≥1.5 × 109/L - Platelets ≥100 × 109/L\n- 14_Parts B, C: Adequate hepatic function: - AST, ALT, ALP ≤3.0×ULN (≤5.0×ULN if patient has liver metastases) - Bilirubin ≤1.5 × ULN (a. up to 2.0 × ULN is allowed if the direct bilirubin level is normal, and the elevation is limited to indirect bilirubin b. Up to 5.0 x ULN in case of Gilbert’s Syndrome)\n- 15_Parts B, C: Adequate renal function: - For PDAC, UC patients: eGFR ≥50 mL/min/1.73 m2 (CKD-EPI) - For ccRCC patients: eGFR >40 mL/min/1.73 m2 (CKD-EPI\n- 16_Parts B, C: Adequate coagulation: - International normalization ratio or prothrombin time ≤1.5xULN and no history of major thrombotic or clinically relevant major bleeding event in the past 6 months putting the subject at high risk of bleeding during the study as assessed by the Investigator\n- 2_Part A, E: Measurable disease as per RECIST v1.1"}

Exclusion criteria

• {"criterion_text":"- 1_Part A, D, E: Known hypersensitivity to the active substance, to any of the excipients of the DPI 4452, or to radiographic contrast agents\n- 19_Part D E: Administration of a radiopharmaceutical with therapeutic intent within a period 6 months prior to injection of [68 Ga Ga DPI-4452]\n- 7_Parts B, C: Known hypersensitivity to the active substance, to any of the excipients of the DPI 4452, or to radiographic contrast agents\n- 20_Part D,E: Patients who received any systemic antineoplastic therapy for the underlying disease and/or any other investigational study within 28 days or 5 half-life periods (whichever is shorter) prior to injection of [ 68 Ga]Ga-DPI-4452\n- 21_Part D, E: 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 patients are not on active antineoplastic therapy.\n- 8_Parts B, C: Bladder outflow obstruction or unmanageable urinary incontinence\n- 9_Parts B, C: Administration of a radiopharmaceutical with therapeutic intent within a period of 6 months prior to injection of [68Ga]Ga-DPI-4452\n- 13_Parts B and C: History of active stomach or duodenum ulcer in the last 2 years, history of gastroesophageal reflux disease (GERD) Grade ≥3 according to NCI-CTCAE and/or known active gastro-intestinal infection, any unresolved prior radiation-induced gastrointestinal injury. History of gastro-intestinal toxicities from prior systemic cancer therapy not responding to medical treatment.\n- 11_Parts B, C: ongoing treatment with sulfonamides and/or coumarin derivatives (e.g., acenocoumarol, warfarin, phenprocoumon) or any previous CA IX-targeting treatment within 2 weeks (or 5 halflives, whichever is longer) prior to the [68Ga]Ga-DPI-4452 injection and [177Lu]Lu DPI 4452 infusion. Patients on stable therapeutic anticoagulation with low molecular weight heparin or direct acting oral anticoagulants without evidence of previous bleeding complications may be eligible upon agreement between Investigator and Sponsor\n- 12_Parts B, C: Prior EBRT to more than 25% of the bone marrow as judged by the Investigator\n- 2_Part A: Bladder outflow obstruction or unmanageable urinary incontinence\n- 3_Part A, E: Administration of a radiopharmaceutical within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]Ga-DPI-4452\n- 22_Part D,E: Prior EBRT to more than 25% of the bone marrow, as judged by the Investigator\n- 23_Part D,E: 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\n- 4_Part A: Previous CA IX-targeting treatment\n- 5_Part A: 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\n- 6_part A, E: Prior external beam radiation therapy (EBRT) to more than 25% of the bone marrow, as judged by the Investigator\n- 14_Part B,C: For patients included in cohorts with acetazolamide, any contra-indication to acetazolamide according to the local product label, including hypersensitivity to acetazolamide or any of its excipients or any other sulfonamides\n- 15_Part D: Renal mass known to be malignant\n- 16_Part D: Uncontrolled intercurrent illness or condition, including but not limited to ongoing or active infection, spinal cord compression, uncontrolled psychiatric disorders, or any clinically significant abnormalities detected during screening laboratory tests, ECG test or physical exams that, in the opinion of the Investigator, would adversely affect the participant's ability to participate in the study\n- 17_Part D, E: Ongoing treatment with sulfonamides and/or coumarin derivatives (e.g., acenocoumarol, warfarin, phenprocoumon) or any previous CA IX-targeting treatment within 2 weeks (or 5 half-lives, whichever is longer) prior to the [68Ga]GaDPI4452 injection"}

Primary endpoints

• {"endpoint_text":"- 1_Part A: Incidence and severity of treatment-emergent adverse events (TEAEs), serious TEAE and laboratory abnormalities graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCICTCAE) v5.0 criteria\n- 2_Part A: Change in vital signs and electrocardiogram (ECG)\n- 3_Part B: Incidence of dose-limiting toxicities (DLTs), cumulative safety, and available data including but not limited to PK data, dosimetry, changes in laboratory values, vital signs, and ECG\n- 4_Part C: Objective Response Rate (ORR) defined as the percentage of patients who achieve a partial response or complete response as measured by RECIST v1.1\n- 5_Part D: Diagnostic concordance between [68Ga]Ga-DPI-4452 uptake by PET imaging in the renal mass and assessment of the histological characteristics of the IDRM\n- 6_Part E: Radiotracer uptake at lesion level, identified via PET/CT imaging\n- 7_Part E: TBR SUVmax/SUVmean of lesion versus reference region","definition_or_measurement_approach":"Part A safety endpoints: graded according to NCI-CTCAE v5.0; vital signs and ECG changes per standard clinical measurements. Part B DLT incidence and cumulative safety including PK and dosimetry assessments. Part C ORR: defined as percentage of patients achieving partial or complete response measured by RECIST v1.1. Part D diagnostic concordance: comparison of PET uptake with histopathology of IDRM. Part E imaging endpoints: lesion-level radiotracer uptake measured by PET/CT and tumour-to-background ratio (TBR) using SUVmax and SUVmean versus a reference region."}

Secondary endpoints

• {"endpoint_text":"- 1_Part A: PK parameters of radioactivity in blood and urine\n- 2_Part A: Radioactivity uptake in normal organs and tumor lesions\n- 3_Part A: Time-Activity Curves from PET/CT images in normal organs and tumor lesions\n- 4_Part A: Whole-body radiation effective dose\n- 5_Part A: Residence time and absorbed and effective doses per organ and tumor lesion\n- 6_Part A: Radioligand [68Ga]Ga-DPI-4452 PET scan time window for optimal imaging\n- 7_Part A: Radiotracer uptake at lesion level, identified via PET/CT imaging\n- 8_Part A: TBR SUVmax/ SUVmean of lesion versus reference region\n- 9_Part A: Number and location of tumor lesions positive detected by [68Ga]Ga- DPI-4452 PET in comparison with the lesions identified by conventional imaging at baseline\n- 10_Part B: Incidence and severity of TEAEs, serious TEAEs, and laboratory abnormalities\n- 11_Part B: Incidence of treatment discontinuations and treatment modifications due to TEAEs and laboratory abnormalities\n- 12_Part B: PK parameters of radioactivity in blood and plasma and in urine\n- 13_Part B: Radioactivity absorption in normal organs and tumor lesions\n- 14_Part B: Residence time and radiation doses absorbed in organs and tumor lesions; identification of dose limiting organ(s)\n- 15_Part B: ORR as measured by RECIST v1.1\n- 16_Part B: OS for patients at the RP2D\n- 17_Part B: Semi-quantitative assessment of radiotracer absorption at lesion level, identified via whole body planar images and/or S SPECT/CT imaging in Cycle 1\n- 18_Part B: Comparison of tumor absorption versus absorption by reference region\n- 19_Part B: 68Ga SUV (max, mean) versus 177Lu absorption in tumoral lesions overall, the lesion with the highest uptake\n- 20_Part B: Concordance between [68Ga]Ga-DPI-4452 uptake by PET imaging (SUVmax, SUVmean) of the hottest lesion(s) and CA IX expression by IHC measured as H score in the available tumor biopsyy/cytological samples, and % of lesions with uptake concordant with the hottest lesion\n- 21_Part B: Radioactivity uptake in normal organs and tumor lesions estimated as radiation absorbed dose (Gy/GBq) and as SUV (max, mean)\n- 22_Part B: Time-Activity Curves from from whole body planar images and/or SPECT/CT images in normal organs and tumor lesions\n- 23_Part B: Residence time and radiation doses absorbed in organs and tumor lesions\n- 24_Part B: Number and location of tumor lesions positive detected by [68Ga]Ga- DPI-4452 PET in comparison with the standard imaging\n- 25_Part B: Incidence and severity of TEAEs, serious TEAEs, and laboratory abnormalities\n- 26_Part C: Incidence and severity of TEAEs, serious TEAEs, and laboratory abnormalities\n- 27_Part C: Incidence of treatment discontinuations and treatment modifications due to TEAEs and laboratory abnormalities\n- 28_Part C: OS\n- 29_Part C: Number and location of PET positive tumor lesions compared with the lesions identified at standard imaging (by RECIST v1.1)\n- 30_Part C: In a subset of patients: PK parameters of radioactivity in blood, plasma and in urine\n- 31_Part C: In a subset of patients: Radioactivity absorption in normal organs and tumor lesions\n- 32_Part C: In a subset of patients: Time-Activity Curves from whole body planar images and/or SPECT/CT images in normal organs and tumor lesions\n- 33_Part C: In a subset of patients: Residence time and radiation doses absorbed in organs and tumor lesions; identification of dose limiting organ(s)\n- 34_In a subset of patients: Semi-quantitative assessment of radiotracer uptake at lesion level, identified via whole body planar images and/or SPECT/CT imaging\n- 35_In a subset of patients: Comparison of tumor absorption versus absorption by reference region\n- 36_In a subset of patients: 68Ga SUV (max, mean) versus 177Lu absorption in tumoral lesions\n- 37_Part C Concordance between [68Ga]Ga-DPI-4452 uptake by PET imaging (SUVmax, SUVmean) of the hottest lesion(s) and CA IX expression by IHC measured as H score in the available tumor biopsyy/cytological samples, and % of lesions with uptake concordant with the hottest lesion\n- 38_Incidence and severity of TEAEs, serious TEAEs, and laboratory abnormalities\n- 39_Parts B, C: Change in vital signs and ECG\n- 40_Parts B, C: PFS rate at 6 months, PFS, DoR and DCR\n- 41_Part D: Sensitivity, specificity, Positive Predictive Value (PPV) and Negative Predicitive Value (NPV) of [68Ga]GaDPI-4452 PET/CT imaging compared to histology\n- 42_Part D: Incidence and severity of TEAEs, serious TEAEs graded according to NCI-CTCAE v5.0 criteria\n- 43_Part E: Number and location of tumor lesions positive detected by [68Ga]Ga-DPI-4452 PET in comparison with the lesions identified by conventional imaging at baseline\n- 44_Part E: Incidence and severity of TEAEs, serious TEAEs graded according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0 criteria","definition_or_measurement_approach":"Secondary endpoints include PK parameters (blood, plasma, urine), radiotracer uptake measures (SUVmax, SUVmean), time-activity curves from PET/CT or planar/SPECT imaging, dosimetry metrics (residence time, absorbed dose Gy/GBq), safety outcomes graded per NCI-CTCAE v5.0, imaging concordance with histology/CA IX IHC (H-score), RECIST v1.1-based tumour response assessments (ORR, PFS, DoR, DCR), overall survival (OS), and diagnostic accuracy metrics (sensitivity, specificity, PPV, NPV) where specified. Many endpoints specify measurement methods (e.g., RECIST v1.1 for ORR; SUV metrics and dosimetry calculations for imaging endpoints; NCI-CTCAE v5.0 for safety grading)."}

France

Earliest CTIS Part Ii Submission Date

02-02-2024

Latest Decision Or Authorization Date

25-03-2024

Processing Time Days

52

Number Of Sites

9

Number Of Participants

85

Belgium

Earliest CTIS Part Ii Submission Date

25-09-2024

Latest Decision Or Authorization Date

09-10-2024

Processing Time Days

14

Number Of Sites

2

Number Of Participants

12

Primary sponsor

Full Name

ITM Oncologics GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

Medpace Finland Oy

Responsibilities

sponsorDuties codes: ["1","10","12","13","2","4","5","7"]

Name

Icon Clinical Research Limited

Responsibilities

sponsorDuties codes: ["13"]

Name

4G Clinical B.V.

Responsibilities

sponsorDuties codes: ["3"]

Name

Almac Clinical Services Limited

Responsibilities

sponsorDuties codes: ["14"]

Third parties

• {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"sponsorDuties codes: [\"7\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United Kingdom (Northern Ireland)","full_name":"Almac Clinical Services Limited","duties_or_roles":"sponsorDuties codes: [\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Caris Mpi Inc.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Austria","full_name":"Seibersdorf Labor GmbH","duties_or_roles":"sponsorDuties codes: [\"14\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Radiopharmaceutical Imaging And Dosimetry LLC","duties_or_roles":"sponsorDuties codes: [\"13\",\"15\"] (value: dosimetry services)","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Asphalion S.L.","duties_or_roles":"sponsorDuties codes: [\"8\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Q2 Solutions LLC","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Netherlands","full_name":"4G Clinical B.V.","duties_or_roles":"sponsorDuties codes: [\"3\"]","organisation_type":"Non-Pharmaceutical company"}
• {"country":"Germany","full_name":"Azenta Germany GmbH","duties_or_roles":"sponsorDuties codes: [\"15\"] (value: long term samples storage)","organisation_type":"Pharmaceutical company"}
• {"country":"Finland","full_name":"Medpace Finland Oy","duties_or_roles":"sponsorDuties codes: [\"1\",\"10\",\"12\",\"13\",\"2\",\"4\",\"5\",\"7\"]","organisation_type":"Pharmaceutical company"}
• {"country":"Spain","full_name":"Anapharm Europe S.L.","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Mosaic Laboratories LLC","duties_or_roles":"sponsorDuties codes: [\"4\"]","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Creative Development Enterprises Inc.","duties_or_roles":"sponsorDuties codes: [\"13\",\"15\"] (value: Dosimetry services)","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [\"13\"]","organisation_type":"Pharmaceutical company"}