[177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake

Phase 1

Active, not recruiting

• Conditions: Neoplasms
• Interventions: Drug: [177Lu]-NeoB; Drug: [68Ga]-NeoB; Drug: LCZ696

• Registration Number: NCT03872778
• Lead Sponsor: Advanced Accelerator Applications

Brief Summary

The purpose of this first-in-human (FIH) study of \[177Lu\]-NeoB is to characterize the safety, tolerability, pharmacokinetics (PK) as well as the distribution and radiation dosimetry, and anti-tumor activity of \[177Lu\]-NeoB in patients with advanced solid tumors known to overexpress Gastrin-Releasing Peptide Receptor (GRPR) and with \[68Ga\]-NeoB lesion uptake.

Detailed Description

This is a Phase I/IIa study which consists of a dose escalation (Phase I) and an expansion part (Phase IIa).

Dose escalation (Phase I):

Phase I study will be conducted in adult patients (age \>= 18 years old) with any of the following selected advanced or metastatic solid tumors: breast cancer, lung cancer, prostate cancer, gastro intestinal stromal tumor (GIST), and glioblastoma (GBM) for whom no standard therapy is available, tolerated or appropriate, and with \[68Ga\]-NeoB lesion uptake as defined in the inclusion criteria.

In Phase I, every effort must be made to include at least one patient of each gender (male/female) in each Dose level to obtain dosimetry data for each gender at all Dose levels tested. However, if it is not feasible, at least 3 patients of each gender must be included in the study before reaching the \[177Lu\]-NeoB Dose level of 100% estimated cumulative dose (ECD) (Dose level 4) or the maximum tolerated dose (MTD) / recommended phase two dose (RP2D), whichever is lower.

Expansion part (Phase IIa):

The Phase IIa study will be conducted in adult patients (age \>= 18 years old) with:

* For Cohorts A, B, C respectively: Any of the following selected advanced or metastatic solid tumors: breast cancer (human receptor (HR)-positive, human epidermal growth factor receptor-2 (HER-2) negative including HER 2 low), prostate cancer, and GIST all showing \[68Ga\]-NeoB lesion uptake.

* For Cohort D: Patients affected by any advanced/metastatic solid tumor type known to overexpress GRPR, including recurrent GBM, and with moderate impaired renal function defined as creatinine clearance (calculated using the Cockcroft-Gault formula, or measured) ≥ 30mL/min and \< 60mL/min.

* For Cohort E (US and UK only): Patients eligible for enrollment in any of the three advanced/metastatic tumor types (as defined for Cohorts A, B, C) who will receive the first cycle of \[177Lu\]-NeoB upon co-administration with LCZ696

* Enrollment in cohort D will no longer be allowed with implementation of protocol version 07. \*\*

Study Timeline

• Study First Submitted: 2019-03-11
• Study First Submitted QC: 2019-03-11
• Study First Posted: 2019-03-13
• Study Start: 2019-07-24
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-23
• Primary Completion: 2025-11-24
• Study Completion: 2026-12-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 51

Inclusion Criteria

1. Signed informed consent must be obtained prior to participation in the study.

2. Adult patients (age ≥ 18 years old) with any of the following advanced or metastatic solid tumors:

   • For Phase I: breast cancer, lung cancer, prostate cancer, GIST, GBM

   • For Phase IIa:

     1. Cohort A: Breast cancer with histology as follows: HR positive with ER > 10% of nuclei stain, HER-2 negative including HER-2 low based on current practice and medical history

     2. Cohort B: Prostate cancer

     3. Cohort C: GIST

     4. Cohort D: Patients affected by any advanced/metastatic solid tumor type known to overexpress GRPR including recurrent GBM, and with moderate impaired renal function defined as creatinine clearance (calculated using the Cockcroft-Gault formula, or measured) ≥ 30 mL/min and < 60 mL/min

        ** Enrollment in cohort D will no longer be allowed with implementation of protocol version 07. **

     5. Cohort E: Breast cancer with histology as follows: HR positive with ER > 10% of nuclei stain, HER-2 negative including HER-2 low as assessed on the primary diagnosis, or prostate cancer, or GIST

3. At least one measurable lesion as per RECIST 1.1, RANO (applicable for GBM only) criteria detected on the low-dose CT or on the MRI (for GBM MRI only) acquired together with the [68Ga]-NeoB PET.

   The same identified measurable lesion shows [68Ga]-NeoB uptake on PET/CT or PET/MRI. If the only matching lesion is located in the bone, the patient will still be eligible.

4. Patients for whom no standard therapy is available, tolerated or appropriate in both Phase I and Phase IIa. Specifically in the Phase IIa breast cancer Cohort A, patients need to have completed at least one prior treatment of endocrine therapy (including CDk4/6i) and at least one prior chemotherapy (unless contraindicated) in the metastatic setting. Patients with prior treatment with trastuzumab deruxtecan, alpelisib or elascestrant are also eligible. In case of confirmed presence of deleterious or suspected deleterious germline BRCA1 or BRCA2 mutation, the patient must also have already received a PARP inhibitor-based therapy.

5. Patient Eastern Cooperative Oncology Group (ECOG) performance status:

   • For Phase I: =< 2
   • For Phase IIa: =< 1

Exclusion Criteria

1. Patients who have not had resolution, except where otherwise stated in the inclusion/ exclusion criteria, of all clinically significant toxic effects of prior systemic cancer therapy, surgery, or radiotherapy to Grade =< 1 (except for alopecia)*.

2. Creatinine clearance (calculated using Cockcroft-Gault formula, or measured)

   1. For Phase I and Phase IIa (Cohort A, B, C, and E): < 60 mL/min or serum creatinine > 1.5 x ULN*
   2. For Phase IIa (Cohort D): < 30 mL/min or >= 60 mL/min

3. Platelet count of < 75 x 109/L*†

4. Absolute neutrophil count (ANC) < 1.0 x 109/L*†

5. Hemoglobin < 9 g/dL*†

6. 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*

7. Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert's syndrome who are eligible if total bilirubin ≤ 3 x ULN*

8. Serum amylase and/or lipase > 1.5 x ULN*

9. Known or expected hypersensitivity to [177Lu]-NeoB, [68Ga]-NeoB or any of their excipients.

10. Impaired cardiac function or clinically significant cardiac disease, including any of the following:

    • Clinically significant and/or uncontrolled heart disease such as congestive heart failure requiring treatment (NYHA grade >= 2), uncontrolled arterial hypertension or clinically significant arrhythmia
    • LVEF < 50% as determined by echocardiogram (ECHO)*
    • QTcF >470 msec for females and QTcF >450 msec for males on screening electrocardiogram (ECG) or congenital long QT syndrome
    • Acute myocardial infarction or unstable angina pectoris < 3 months prior to [177Lu]-NeoB (IMP1) administration

11. Patients with diabetes mellitus not stable under current treatment as judged by the investigator or with hyperglycemia ≥ CTCAE version 5.0 Grade 2*.

12. Patients with history of or ongoing acute or chronic pancreatitis.

13. Concurrent bladder outflow obstruction or unmanageable urinary incontinence.

14. Administration of a radiopharmaceutical with therapeutic intent within a period corresponding to 10 half-lives of the radionuclide used prior to injection of [68Ga]-NeoB (IMP2).

15. Prior External Beam Radiation Therapy (EBRT) to more than 25% of the bone marrow.

16. [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).

17. [Removed]

18. 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 ≤ 14 days (whichever is shorter) prior to starting [177Lu]-NeoB treatment

19. History of somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study.

20. 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.

21. Pregnant or breast-feeding women

22. 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 7 months after study drug discontinuation. Highly effective contraception methods include:

    • True abstinence, when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods), declaration of abstinence for the duration of exposure to IMPs, and withdrawal are not acceptable methods of contraception.

    • Male or female sterilization. Vasectomised partner is a highly effective birth control method if the partner is the sole sexual partner of the study participant and the vasectomised partner has received medical assessment of the surgical success.

    • Women tubal ligation is an acceptable highly effective contraception method, but surgical sterility is defined as bilateral salpingectomy (or bilateral oophorectomy or hysterectomy).

    • Combination of any two of the following (a+b or a+c or b+c):

      1. Use of oral, injected, or implanted hormonal methods of contraception. In case of use of oral contraception, women should be stable on the same pill for a minimum of 3 months before taking [177Lu]-NeoB treatment. This is not applicable for patients with breast cancer.
      2. Placement of an intrauterine device (IUD) or intrauterine system (IUS). IUS is not applicable for patients with breast cancer.
      3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository Post-menopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months of spontaneous amenorrhea with serum Follicle-Stimulating Hormone (FSH) levels > 40 mIU/mL [for US only: and estradiol < 20 pg/mL] or have had surgical bilateral oophorectomy or bilateral salpingectomy or hysterectomy or tubal ligation at least six weeks prior to screening. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment is she considered not of childbearing potential.

    Sexually active males must use a condom during intercourse while taking the drug and for 4 months after stopping treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid. Female partners of childbearing potential should use highly effective contraceptive methods during and up to 4 months after stopping treatment.

23. Use of other investigational drugs within 30 days prior to informed consent signature.

24. Cohorts A, B, and C: Patient currently receiving NEP inhibitors (e.g., Entresto, racecadotril) and for whom images for dosimetry assessments cannot be acquired.

25. Cohort E only: Patient meeting at least one of the following conditions

    • Currently receiving NEP inhibitors (e.g., Entresto, racecadotril)

    • Known history of angioedema related to previous angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) therapy or hereditary or idiopathic angioedema

    • Hypersensitivity to the LCZ696 active substances or to any of the excipients

    • Diabetes mellitus and receiving aliskiren-containing medicinal products

    • Receiving ACE inhibitors or has discontinued ACE inhibitor therapy within 36 hours before receiving the first dose of LCZ696 in the study

    • Systolic blood pressure < 100 mmHg¥

    • Serum potassium level > 5.5 mEq/L¥

      • To be considered as valid to determine the eligibility of a patient, exam results of exclusion criteria #2, #3, #4, #5, #6, #7, #8, #10 (except LVEF) and #11 must be collected on or after date of patient's informed consent and must be available in the source documents for monitoring. LVEF evaluation is permitted within 6 weeks prior to IMP1 administration, even if performed outside the screening period as part of standard routine clinical practice of care, before ICF signature.

        • No platelet transfusion, packed red cell transfusion, or G-CSF will be allowed during the selection phase after ICF signature. Transfusion for the sole purpose of making a patient eligible for the study inclusion is not allowed.

          • Blood pressure and serum potassium level must be evaluated at screening and again at time of LCZ696 collection, within 7 days prior to [177Lu]-NeoB first administration (C1D1).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Phase I: Cohort III	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 80% ECD for 3 cycles (q6w)
Phase I: Cohort IV	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 100% ECD for 3 cycles (q6w)
Phase I: Cohort V	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 120% ECD for 3 cycles (q6w)
Phase IIa: Cohort B	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase I: Cohort II	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 60% ECD for 3 cycles (q6w)
Phase IIa: Cohort C	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase IIa: Cohort D	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase IIa:Cohort E	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w LCZ696: co-administered with \[177Lu\]-NeoB
Phase IIa:Cohort E	LCZ696	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w LCZ696: co-administered with \[177Lu\]-NeoB
Phase I: Cohort I	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 50 mCi (1.85 GBq) cycle 1, 60% Estimated Cumulative Dose (ECD) for cycles 2-4, q6w
Phase IIa: Cohort A	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase IIa:Cohort E	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w LCZ696: co-administered with \[177Lu\]-NeoB
Phase IIa: Cohort C	[68Ga]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase I: Cohort V	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 120% ECD for 3 cycles (q6w)
Phase IIa: Cohort A	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase I: Cohort II	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 60% ECD for 3 cycles (q6w)
Phase I: Cohort III	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 80% ECD for 3 cycles (q6w)
Phase I: Cohort IV	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 100% ECD for 3 cycles (q6w)
Phase IIa: Cohort D	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase IIa: Cohort B	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: dose TBD based on Cohorts I-VI, 3 cycles q6w
Phase I: Cohort I	[177Lu]-NeoB	\[68 Ga\]-NeoB: 50 micrograms/dose at screening \[177Lu\]-NeoB: 50 mCi (1.85 GBq) cycle 1, 60% Estimated Cumulative Dose (ECD) for cycles 2-4, q6w

Primary Outcome Measures

Name	Time	Method
Phase I: Incidence of dose limiting toxicities (DLTs) of [177Lu]-NeoB	Within 42 days following the first administration of [177Lu]-NeoB	A dose-limiting toxicity (DLT) is defined as a clinically relevant adverse event or abnormal laboratory value not attributable to the disease or disease-related processes under investigation, considered possibly related to \[177Lu\]-NeoB that occurs within 42 days following the first administration of \[177Lu\]-NeoB (cycle 1) and meets any of the criteria listed in Table 6-4 (Criteria for defining dose-limiting toxicities).
Phase I: Determination of Maximum Tolerated Dose (MTD)/ Recommended phase two dose (RP2D) of [177Lu]-NeoB	Within 42 days following the first administration of [177Lu]-NeoB	The maximum tolerated dose (MTD) and/or the recommended phase II dose (RP2D) of \[177Lu\]-NeoB will be identified: 1. MTD is defined as the lowest single dose at which 25% or more of the patients experienced a DLT during the first cycle (6 weeks).; 2. RP2D is defined as the single dose level below the MTD. The number of cycles recommended for Phase II will be defined based on the cumulative dose toxicities reported during Phase I.
Phase IIa (Cohort E): Absorbed radiation doses of [177Lu]-NeoB in organs and tumor lesions	6 weeks	Absorbed radiation doses in organs and tumor lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
Phase IIa (Cohorts A, B and C): Individual clinical responses assessed by Response Evaluation Criteria In Solid Tumors (RECIST v1.1)	25 months	To assess the anti-tumor activity of \[177Lu\]-NeoB at the RP2D across different solid tumors
Phase IIa (Cohort E): Concentration of [177Lu]-NeoB in blood over time and derived PK parameters	6 weeks	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Concentration of \[177Lu\]-NeoB will be listed and summarized using descriptive statistics.

Secondary Outcome Measures

Name	Time	Method
Phase I: Absorbed radiation doses of [177Lu]-NeoB in critical organs	6 weeks	Absorbed radiation doses in critical organs (e.g. kidneys, bone marrow, pancreas) will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
Phase IIa (Cohorts A, B and C): Concentration of [177Lu]-NeoB in blood over time and derived PK parameters	6 weeks	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Concentration of \[177Lu\]-NeoB will be listed and summarized using descriptive statistics.
Phase IIa (Cohorts A, B and C): Changes from baseline in European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30)	15 months	The QLQ-C30 is composed of both multi-item scales and single-item measures. These include five functional scales, three symptom scales, a global health status / QoL scale, and six single items. Each of the multi-item scales includes a different set of items - no item occurs in more than one scale. All of the scales and single-item measures range in score from 0 to 100. A higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient).
Phase I: Tissue Activity Curves (ACs)	6 weeks	Tissue activity curves (ACs) will be 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.
Phase I and Phase IIa: Dose interruptions and modifications	25 months
Phase I: Time Activity Curves (ACs)	6 weeks	Time Activity Curves (ACs) describe the percentage of the activity injected versus time.
Phase I: Half-life of [177Lu]-NeoB in blood	6 weeks	Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics.
Phase IIa (Cohort E): Dose interruptions and modifications for [177Lu]-NeoB when co-administered with the NEPi LCZ696 in Cycle 1	Within 42 days following the first administration of [177Lu]-NeoB (Cycle 1)
Phase I: Residence time of [177Lu]-NeoB in organs and tumor lesions	6 weeks	Residence time in organs and tumors lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
Phase I: Individual objective response and Duration of Response (DOR)	25 months	DOR is defined as the duration of time between the date of first documented response (CR or PR) in soft tissue according to PCWG3 modified RECIST 1.1, and the date of first documented progression or death due to any cause.
Phase I and Phase IIa: Adverse Events for [177Lu]-NeoB	25 months	The distribution of adverse events for \[177Lu\]-NeoB as monotherapy will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Phase I: Urinary excretion of [177Lu]-NeoB	6 weeks	Urine samples will be collected over specified time intervals and analyzed for radioactivity using a gamma counter. The radioactivity excreted in urine will be summarized using descriptive statistics.
Phase IIa (Cohorts A, B and C): Absorbed radiation doses of [177Lu]-NeoB in organs and tumor lesions	6 weeks	Absorbed radiation doses in organs and tumor lesions will be summarized with descriptive statistics. Lesion number will be assigned by dosimetry expert.
Phase I and Phase IIa: Adverse Events for [68Ga]-NeoB	25 months	The distribution of adverse events for \[68Ga\]-NeoB will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
Phase IIa (Cohort E): Adverse Events for [177Lu]-NeoB when co-administered with the NEPi LCZ696 in Cycle 1	25 months	The distribution of adverse events for \[177Lu\]-NeoB when co-administered with the neprilysin inhibitor (NEPi) LCZ696 will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.

Trial Locations

Locations (11)

City of Hope; 🇺🇸 Duarte, California, United States

Stanford University; 🇺🇸 Stanford, California, United States

John Hopkins University; 🇺🇸 Baltimore, Maryland, United States

Oregon Health & Science University; 🇺🇸 Portland, Oregon, United States

Pittsburgh University; 🇺🇸 Pittsburgh, Pennsylvania, United States

MD Anderson Cancer Center; 🇺🇸 Houston, Texas, United States

Medical University of Innsbruck; 🇦🇹 Innsbruck, Austria

CHU de Grenoble; 🇫🇷 La Tronche, France

Erasmus MC; 🇳🇱 Rotterdam, Netherlands

Vall d'Hebron Institute of Oncology; 🇪🇸 Barcelona, Spain

Addenbroke's hospital; 🇬🇧 Cambridge, United Kingdom