E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Solid tumors known to overexpress GRPR and with [68Ga]-NeoB lesion uptake |
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E.1.1.1 | Medical condition in easily understood language |
Solid tumors expressing a specific target (GRPR) identified by [68Ga]-NeoB and for treatment with [177Lu]-NeoB |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Phase I: • To identify the maximum tolerated dose (MTD) and/or Recommended Phase II dose (RP2D) of [177Lu]-NeoB
Phase IIa: • To assess the Disease Control Rate (DCR) at week 20 of [177Lu]-NeoB at the RP2D
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E.2.2 | Secondary objectives of the trial |
Phase I: • To assess the PK as well as the distribution and radiation dosimetry of each dose level of [177Lu]-NeoB • To assess the preliminary anti-tumor activity of [177Lu]-NeoB
Phase IIa: • To assess quality of life of patients via EORTC QLQ-C30 Questionnaire • To further assess the anti-tumor activity of [177Lu]-NeoB Phase I and IIa: • To characterize the safety and tolerability of [177Lu]-NeoB • To further characterize the safety and tolerability of [68Ga]-NeoB
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study. 2. Adult patients with advanced solid tumors known to overexpress GRPR. 3. [68Ga]-NeoB tumor lesion uptake on PET/CT or PET/MRI scan during Selection phase (≥ 50% of lesions detectable with dose CT or MRI acquired together with the [68Ga]-NeoB PET have to be [68Ga]-NeoB positive) 4. At least one measurable lesion per RECIST 1.1/RANO with a [68Ga]-NeoB uptake. 5. Patients for whom no standard therapy is available, tolerated or appropriate. 6. Presence of at least one detacble tumor lesion confirmed with CT or MRI acquired together with the [68Ga]-NeoB PET. 7. Patient Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2. 8. Life expectancy more than 6 months.
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E.4 | Principal exclusion criteria |
1. Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60 mL/min or serum creatinine >1.5 x ULN. 2. Platelet count of < 75 x 109/L . 3. Absolute neutrophil count (ANC) < 1.0 x 109/L. 4. Hemoglobin < 9 g/dL. 5. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x upper limit of normal (ULN) if no demonstrable liver metastases or > 5 x ULN in the presence of liver metastases. 6. Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert’s syndrome who are eligible if total bilirubin ≤ 3 x ULN. 7. Serum amylase and/or lipase > 1.5 x ULN. 8. Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of their excipients. 9. Impaired cardiac function or clinically significant cardiac disease 10. Patients with diabetes mellitus requiring insulin treatment and/or with clinical signs or with fasting plasma glucose >160 mg/dL (8.9 mmol/L). 11. Patients with history of or ongoing acute or chronic pancreatitis. 12. Prior administration of a radiopharmaceutical with therapeutic intent within a period corresponding to 10 half-lives of the radionuclide used in such radiopharmaceutical. 13. Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow. 14. [223Ra]-therapy within the context of diffuse bone or bone-marrow involvement (i.e. “superscan” defined as bone scintigraphy in which there is excessive skeletal radioisotope uptake [>20 bone lesions] in relation to soft tissues along with absent or faint activity in the genitourinary tract due to diffuse bone/ bone marrow metastases. 15. Patients who have changed the dose of systemic steroid therapy within less than 2 weeks prior to [68Ga]-NeoB (IMP2) administration or patients for whom steroid dose increase is anticipated during the study. 16. Patients who have received prior systemic anti-cancer treatment within the following time frames: • Cyclical chemotherapy within a period that is shorter than the cycle length used for that treatment (e.g. 6 weeks for nitrosourea, mitomycin-C) prior to starting [177Lu]-NeoB treatment • Biologic therapy (e.g. antibodies), continuous or intermittent small molecule therapeutics, or any other investigational agents within a period which is ≤ 5 T1/2 or ≤ 4 weeks (whichever is shorter) prior to starting [177Lu]-NeoB treatment. 17. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study. 18. Malignant disease, other than that being treated in this study. Exceptions to this exclusion include the following: malignancies that were treated curatively and have not recurred within 2 years prior to [177Lu]-NeoB treatment; completely resected basal cell and squamous cell skin cancers; any malignancy considered to be indolent and that has never required therapy; and completely resected carcinoma in situ of any type. 19. Pregnant or breast-feeding women 20. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, are not allowed to participate in this study UNLESS they are using highly effective methods of contraception throughout the study and for 6 months after study drug discontinuation. 21. Concurrent bladder outflow obstruction or unmanageable urinary incontinence.
For more details, please refer to protocol |
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E.5 End points |
E.5.1 | Primary end point(s) |
Phase I • Incidence and nature of dose limiting toxicities (DLTs)
Phase IIa • DCR at week 20 as assessed by Response Evaluation Criteria In Solid Tumors (RECIST v1.1) for solid tumors or as per response assessment in Neuro-Oncology (RANO) Criteria for glioma indication.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Phase I • End of DLT period of last patient (each cohort)
Phase IIa • Week 20 |
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E.5.2 | Secondary end point(s) |
Phase I • Tissue Activity Curves (ACs) generated from the amount of radioactivity in one given tissue at a given moment over the amount of radioactivity present in the blood at that given moment • Time ACs, describing % of the activity amount injected vs. time will be derived. • Absorbed radiation doses of [177Lu]-NeoB in critical organs (e.g. kidneys, bone marrow, pancreas) • Urinary excretion of [177Lu]-NeoB • Half-life of [177Lu]-NeoB in blood • Residence times of [177Lu]-NeoB in organs and tumor lesions • DCR, Objective response rate (ORR), Duration of Response (DOR)
Phase IIa • Changes from baseline in EORTC QLQ-C30 • Objective response rate (ORR), Duration of Response (DOR), Progression Free Survival (PFS) as assessed by RECIST version 1.1 or RANO and OS Phase I and IIa: • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs • Dose interruptions and modifications • Adverse events, serious adverse events, changes in hematology and chemistry values, vital signs, ECGs
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Phase I • Last patient last visit
Phase IIa • Last patient last visit |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Yes |
E.7.1.1 | First administration to humans | Yes |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 4 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Austria |
Germany |
Netherlands |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The end of the clinical trial is defined as the last visit of the last patient. |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 35 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial months | 37 |