A Phase I/II, Dose Finding and Optimization Study of [177Lu]Lu-NeoB in Combination With Capecitabine in Patients With GRPR+, ER+, HER2- Metastatic Breast Cancer After Progression on Previous Endocrine Therapy in Combination With a CDK4/6 Inhibitor.

Inclusion Criteria:

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

2. Participant is female or male adult ≥ 18 years old at the time of informedconsent(s).

3. Participant has a histologically and/or cytologically documented diagnosis of ER+breast cancer (ER expression >10% of tumor cell nuclei stain (regardless of PgRexpression) (based on the most recently analyzed tissue sample tested by a locallaboratory).

4. Participant has HER2-negative (as per ASCO-CAP guidelines Wolff et al 2018) breastcancer defined as a negative in situ hybridization test (ISH) or an IHC status of 0, 1+ or 2+. If IHC is 2+, a negative ISH (e.g., FISH, CISH, or SISH) (based on themost recently analyzed tissue sample tested by a local laboratory) is required.

5a. Participant received no more than three prior endocrine therapies (single agent or in combination with targeted therapy) regimen/s in the metastatic setting of which at least one included endocrine therapy in combination with a CDK4/6i. In addition:

• in case of confirmed presence of deleterious or suspected deleterious germline BRCA1or BRCA2 mutation, the participant may also have received a PARP inhibitor-basedtherapy.

• In case of HER2-low breast cancer (IHC 1+ or IHC 2+ with ISH negative as perASCO-CAP guidelines Wolff et al 2023), the participant may also have receivedtrastuzumab deruxtecan [Enhertu®]).

6. Participant has metastatic breast cancer with radiologically confirmedprogression of disease after the most recent therapy 7. Participant must havemeasurable disease, i.e., at least one measurable lesion as per RECIST 1.1. (alesion at a previously irradiated site may only be counted as a target lesionif there is a clear sign of progression since the irradiation) as per localassessment.

Note: If only lytic bone lesions are present, they must have at least one lesion with a soft tissue component that can be evaluated by CT or MRI and meets the definition of measurability as per RECIST 1.1 criteria (participants with only one predominantly lytic bone lesion that has been previously irradiated are eligible if there is documented evidence of disease progression of the bone lesion after irradiation).

8a. Participant has at least one target lesion [as per RECIST 1.1 and based on the baseline stand-alone contrast-enhanced CT (or MRI)] with [68Ga]Ga-NeoB uptake greater than the physiological uptake of the liver at PET/CT or PET/MRI, as per local reading. In addition:

• Participants with liver or lung disease involvement must show [68Ga]Ga-NeoB uptake greater than the physiological uptake of the liver as follows:

• If there is liver disease involvement (in the absence of lung involvement), in ≥ 50%of all CT measurable liver lesions (RECIST 1.1)

• If there is lung disease involvement (in the absence of liver involvement), in ≥ 50%of all CT measurable lung lesions (RECIST 1.1)

• Participants with both liver and lung disease involvement must show [68Ga]Ga-NeoBuptake above the liver in ≥ 50% of all CT measurable lesions either in liver or lung (RECIST 1.1) and in at least one measurable lesion in the remaining organ (lung orliver) 9a. Participants with central nervous system (CNS) involvement are eligibleprovided that they meet ALL the following criteria:

• At least 2 weeks from prior therapy completion (including radiation and/or surgery)to initiation of the study treatment

• Clinically stable CNS tumor at the time of screening

• Participant is not receiving steroids and/or anti-epileptic medications for brainmetastases at the time of initiation of the radioligand study treatment 10.Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of 0or 1.

11. Participant has adequate bone marrow and organ function as defined by thefollowing laboratory values (as assessed by local laboratory):

• Absolute neutrophil count ≥ 1.5 × 109/L

• Platelets ≥ 100 × 109/L

• Hemoglobin ≥ 9.0 g/dL

• International Normalized Ratio (INR) ≤1.5

• Creatinine Clearance ≥60 mL/min using the Chronic Kidney Disease EpidemiologyCollaboration (CKD-EPI) equation

• Total bilirubin (TBIL) < 1.5 × ULN (any elevated bilirubin should be asymptomatic atenrollment) except for participants with Gilbert's syndrome who may only be includedif the total bilirubin is ≤ 3.0 × ULN or direct bilirubin ≤ 1.5 × ULN

• In absence of liver metastases, alanine aminotransferase (ALT) and aspartateaminotransferase (AST) < 2.5 × ULN. If the participant has liver metastases, theparticipant will be eligible for the study if ALT and AST < 5 X ULN.

• Serum lipase ≤ 1.5 × ULN Note: no platelet transfusion, packed red blood celltransfusion, or G-CSF will be allowed during the screening phase after ICF signature

• Participant must have the following laboratory values within normal limits orcorrected to within normal limits with supplements before the first dose of studymedication:

• Potassium

• Magnesium

• Total Calcium (corrected for serum albumin) 12. Participant must be able to swallowcapecitabine tablets. 13. Participant must be able to communicate with theinvestigator and comply with the requirements of the study procedures.

14a. For Phase I part only Female participant must be in postmenopausal status atthe time of starting study treatment.

Postmenopausal status is defined by any of the following (NCCN 2024):

• Prior surgical bilateral oophorectomy (with or without hysterectomy)

• Age ≥ 60 years

• Age < 60 years and ≥ 12 months of natural (spontaneous) amenorrhea in the absence ofchemotherapy, tamoxifen, toremifene, or ovarian suppression with serumFollicle-Stimulating Hormone (FSH) and estradiol in the postmenopausal range perlocal normal range.

• Aged < 60 years: chemotherapy-induced amenorrhea for ≥ 12 months with serialmeasurements of FSH and estradiol in post-menopausal ranges (NCCN V4 2023).

• Aged < 60 years: on tamoxifen with serial measurements of FSH and estradiol inpost-menopausal ranges Note: Ovarian radiation or treatment with a gonadotropinreleasing hormone agonist (GnRHas e.g. goserelin acetate) is not permitted forinduction of ovarian suppression in the Phase I part.

Male participants, provided that they do not require continued GnRHas while on study treatment 15a. For Phase II part only

• Female participant is post-menopausal as per criteria above at the time of starting study treatment.

OR • Female participant is pre/peri-menopausal at the time of starting study treatment

Pre-menopausal status is defined as either:

• Patient had last menstrual period within the last 12 months OR

• If on tamoxifen or toremifene within the past 14 days, FSH and estradiol inpre-menopausal ranges on serial measurements OR

• In case of therapy induced amenorrhea, FSH and estradiol in pre-menopausal ranges onserial measurements Note: Peri-menopausal status is defined as neitherpre-menopausal nor post-menopausal (see definition above)

• Male participants, regardless of their need of GnRHas while on study treatment.

Exclusion Criteria:

1. Participant with symptomatic visceral disease or any disease burden that are at riskof life-threatening complications as per the investigator's judgment.

2a. Participant has received >1 prior treatment with chemotherapy and/or Antibody Drug-Conjugates (ADCs) in the metastatic setting. Chemotherapy in neoadjuvant/ adjuvant setting is not considered a line of therapy, unless progression or recurrence occurred during or within 12 months after completion of adjuvant chemotherapy.

3. Participant has received prior treatment with capecitabine. 4. History ofhypersensitivity or contraindication to any of the study treatments or theirexcipients or to drugs of similar chemical classes.

4. Participant has inflammatory breast cancer at screening. 6. Participant has hadmajor surgery within 14 days prior to starting study treatment or has not recoveredfrom major side effects.

5. Participant has received any prior treatment with a therapeutic radiopharmaceutical.

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

7. Participant has a concurrent malignancy or malignancy within 3 years of start ofstudy treatment, with the exception of adequately treated, basal or squamous cellcarcinoma, non-melanomatous skin cancer, or curatively resected cervical cancer.

8. Participant has impairment of gastrointestinal (GI) function or GI disease that maysignificantly alter the absorption of the study drugs (e.g., uncontrolled ulcerativediseases, uncontrolled nausea, vomiting, diarrhoea, malabsorption syndrome, or smallbowel resection) based on investigator's discretion.

9. Participant has any other concurrent severe and/or uncontrolled medical conditionthat would, in the investigator's judgment, cause unacceptable safety risks,contraindicate participant participation in the clinical study or compromisecompliance with the protocol (e.g., chronic pancreatitis, chronic active hepatitis,active untreated or uncontrolled fungal, bacterial or viral infections, interstitiallung disease (ILD)/ pneumonitis etc.).

10. Participant has a history of or ongoing acute pancreatitis within 1 year ofscreening.

11. History or current diagnosis of impaired cardiac function, clinically significantcardiac disease or ECG abnormalities indicating significant risk of safety forparticipants in the study such as:

• Documented myocardial infarction (MI), angina pectoris, cardiomyopathy, symptomaticpericarditis, or coronary artery bypass graft (CABG) within 6 months prior to studyentry

• Clinically significant cardiac arrhythmias (e.g., ventricular tachycardia), completeleft bundle branch block, high-grade atrioventricular (AV) block (e.g., bifascicularblock, Mobitz type II and third-degree AV block)

• Long QT syndrome or family history of idiopathic sudden death or congenital long QTsyndrome, or any of the following:

• Risk factors for TdP including uncorrected hypocalcemia, hypokalemia orhypomagnesemia, history of cardiac failure, or history of clinicallysignificant/symptomatic bradycardia

• Inability to determine the Fridericia QT correction formula (QTcF) interval

• Resting QTcF ≥450 msec (male) or ≥460 msec (female) at screening as per standard 12-lead ECG values defined as the mean of the triplicate ECGs and assessed locally

• Left Ventricular Ejection Fraction (LVEF) < 50% as determined by echocardiogram (ECHO) or MUGA.

• Uncontrolled hypertension defined by a Systolic Blood Pressure (SBP) ≥ 160 mmHgand/or Diastolic Blood Pressure (DBP) ≥ 100 mm Hg, with or without anti-hypertensivemedication.

14. Participant is currently receiving brivudine which cannot be discontinued atleast 4-week prior to start of capecitabine therapy.

15a. Participant is currently receiving NEP inhibitors (i.e., Entresto®,racecadotril) and images for dosimetry assessments cannot be acquired for thisparticipant as per Section 8.7.3.

16a. Participant with deficiency or family history of deficiency ofdihydropyrimidine dehydrogenase.

17. Participant participated in a prior investigational study within 30 days priorto start of study treatment, or within 5 half-lives of the investigationalproduct, whichever is longer; or as required by local regulations.

18. Sexually active male participants unwilling to:

• remain abstinent (refrain from sexual intercourse) or

• use a condom, while taking study treatment and for at least 4 months after the lastadministration of [177Lu]Lu-NeoB, or 3 months after the last dose of capecitabine (or as per locally prescribing information) whichever is longer, in addition to thehighly effective method used by the partner who is a female of child-bearingpotential.

Note: A condom is required for all sexually active male participants to prevent them from fathering a child and to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants must not donate sperm for the time period specified above.

19. Participants with legal incapacity to give informed consent, where required by localregulation (e.g. in EU).

20a. For Phase II part only

• Pregnant or breast-feeding women

• Women of childbearing potential, defined as all women physiologically capable ofbecoming pregnant, are not allowed to participate in this study UNLESS they areusing highly effective methods of contraception throughout the study and for up to 7months after the last administration of [177Lu]Lu-NeoB or 6 months after the lastdose of capecitabine (or as per locally prescribing information) whichever islonger. Highly effective contraception methods include:

• Total abstinence (when this is in line with the preferred and usual lifestyle of thesubject). Periodic abstinence (e.g., calendar, ovulation, symptothermal,post-ovulation methods) and withdrawal are not acceptable methods of contraception.

• Bilateral oophorectomy with or without hysterectomy, total hysterectomy, orbilateral salpingectomy at least six weeks before taking study treatment. In case ofoophorectomy alone, only when the reproductive status of the woman has beenconfirmed by follow up hormone level assessment are they not considered to be ofchildbearing potential.

• Bilateral tubal occlusion, Bilateral tubal ligation (at least six weeks beforetaking study treatment)..

• Sterilization (vasectomy) of male partner(s) of the female participant at least 6months prior to screening provided partner(s) has(have) received medical assessmentof the surgical success.

• Placement of an intrauterine device (IUD) and concurrent use of barrier methods ofcontraception: condom or occlusive cap (diaphragm or cervical/vault caps) withspermicidal foam/gel/film/cream/vaginal suppository.

If local regulations deviate from the recommendations provided above, local regulations apply and will be described in the ICF.

Women are considered not of child-bearing potential if they are post- menopausal or have had surgical bilateral oophorectomy (with or without hysterectomy), bilateral salpingectomy or total hysterectomy at least six weeks prior to enrollment on study. 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 to be not of child-bearing potential.

Note: Use of oral (estrogen and progesterone), injected or implanted hormonal methods of contraception or intrauterine system (IUS) or any other form of hormonal contraception for example hormone vaginal ring, or transdermal hormone contraception is not allowed in this study.

21.Participants taking prohibited therapies as listed in Section 6.8.2