AAA603 / Novartis - LARVOL DELTA

Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Nov 2028 ➔ Aug 2027 | Trial primary completion date: Nov 2028 ➔ Aug 2027

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Enhancing Prostate Cancer Care Through Tandem PSMA- and GRPR-targeted Radionuclide Treatment (EANM 2026) - "Secondly, the binding affinity, uptake, retention, and therapeutic effect of [161Tb]Tb-NeoB vs. [177Lu]Lu-NeoB was determined in PCa cell line PC-3 (GRPR+/PSMA-) and PCa tissues to select the best radionuclide for GRPR-TRT... The first steps towards a tandem PSMA/GRPR-TRT strategy, i.e. (1) simultaneous detection of terbium-161 and lutetium-177 labelled radiopharmaceuticals for future patient selection and dosimetry, (2) selection of suitable radionuclides for TRT, and (3) assessing the biological effect of co-incubation on uptake, were successfully taken. Next, efficacy studies in homo- and heterotypic spheroids, the latter representing target heterogeneity, will be performed to determine the best treatment schedule for tandem PSMA-/GRPR-TRT."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • GRP-10

CAAA603D12101: 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. (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Sep 2031 ➔ Apr 2027 | Trial primary completion date: Sep 2031 ➔ Apr 2027

Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2

Targeted radionuclide-drug conjugates: Current status and perspectives. (PubMed, Eur J Med Chem) - "These platforms include 68Ga/177Lu-PSMA systems, 68Ga/177Lu-DOTATATE or OPS202/OPS201 pairs, 68Ga/177Lu-NeoBOMB1, and 18F/177Lu-fibroblast activation protein inhibitor (FAPI) systems. Despite their potential to improve patient stratification and therapeutic efficacy while reducing systemic toxicity, RDCs face substantial challenges, including tumor heterogeneity, radiochemical instability, renal toxicity, and constraints on the large-scale production of radionuclides. Future advances will depend on the development of multitargeting strategies, novel radionuclides, and artificial intelligence (AI)-assisted rational design."

Journal • Review • Oncology • CCKBR • GRP-10 • SSTR

CAAA603B12101: [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=22 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=48 ➔ 22

Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

CAAA603D12101: 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. (clinicaltrials.gov) - P1/2 | N=20 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting | N=58 ➔ 20

Enrollment change • Enrollment closed • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2

CAAA603B12101: [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting

Enrollment open • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

NeoRay phase IIa results: A study of [177Lu]Lu-NeoB (177Lu-NeoB) in pts with advanced solid tumors overexpressing gastrin-releasing peptide receptor (GRPR). (ASCO 2026) - P1/2 | " This Ph IIa, open-label, multicenter, dosage expansion study enrolled 5 adult cohorts with confirmed [68Ga]Ga-NeoB tumor uptake: A) HR+/HER2- breast cancer; B) prostate cancer (PCa); C) gastrointestinal stromal tumor (GIST); D) impaired renal function; and E) pts eligible for Cohorts A–C who also received sacubitril/valsartan (49/51 mg) at Cycle 1 to assess drug-drug interaction (DDI). NeoRay Ph IIa data at the 177Lu-NeoB RP2D (9.25 GBq) reinforce Ph I dosimetry and safety results and support further clinical evaluation. Most AEs were mild/moderate and no new safety signals were identified. Despite the limited sample size, preliminary signs of antitumor activity were observed."

Clinical • First-in-human • Metastases • P2a data • Breast Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Liver Failure • Musculoskeletal Pain • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • GRP-10 • HER-2

CAAA603B12101: [177Lu]Lu-NeoB in Combination With Ribociclib and Fulvestrant in Participants With ER+, HER2- and GRPR+ Advanced Breast Cancer (clinicaltrials.gov) - P1 | N=48 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2 • PGR

Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=42 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jul 2032 ➔ Nov 2028 | Trial primary completion date: Dec 2026 ➔ Nov 2028

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

Trial in progress: Evaluation of the safety, tolerability, whole-body distribution, radiation dosimetry and antitumor activity of 177Lu-NeoB in patients with advanced solid tumors expressing gastrin-releasing peptide receptor (GRPR) (AACR 2024) - P1/2 | "Patients will be treated with [177Lu]-NeoB at the recommended Phase II dose (9.25 GBq [250 mCi]) for a minimum of 2 treatment cycles, each lasting 6 weeks.The primary endpoints are assessment of the disease control rate with [177Lu]-NeoB in cohorts A, B and C, and evaluation of the pharmacokinetics (PK), biodistribution and radiation dosimetry in patients with impaired renal function (Cohort D). Secondary endpoints include assessment of the antitumor activity, PK, distribution, radiation dosimetry, and impact on the quality of life of patients in the [177Lu]-NeoB cohorts (A, B and C) as well as the safety and tolerability of both [177Lu]-NeoB and [68Ga]-NeoB across all cohorts."

Clinical • First-in-human • Metastases • Brain Cancer • Breast Cancer • CNS Tumor • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Glioblastoma • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • GRP-10 • HER-2

NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer. (clinicaltrials.gov) - P1 | N=31 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Jun 2027 ➔ Aug 2026 | Trial primary completion date: Jun 2027 ➔ Aug 2026

Trial completion date • Trial primary completion date • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CHGA • PTEN • RB1 • SSTR2 • SYP • TP53

NEPC Study: An Exploratory Safety and Efficacy Study With PSMA, SSTR2 and GRPR Targeted Radioligand Therapy in Metastatic Neuroendocrine Prostate Cancer. (clinicaltrials.gov) - P1 | N=28 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor • CHGA • PTEN • RB1 • SSTR2 • SYP • TP53

Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=40 | Active, not recruiting | Sponsor: Novartis Pharmaceuticals | Recruiting ➔ Active, not recruiting

Enrollment closed • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

NeoRay: [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake (clinicaltrials.gov) - P1/2 | N=35 | Completed | Sponsor: Advanced Accelerator Applications | N=71 ➔ 35

Enrollment change • First-in-human • Breast Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor

NeoRay: [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-neoB Lesion Uptake (clinicaltrials.gov) - P1/2 | N=71 | Completed | Sponsor: Advanced Accelerator Applications | Active, not recruiting ➔ Completed | N=51 ➔ 71 | Trial completion date: Dec 2026 ➔ Nov 2025 | Trial primary completion date: Nov 2025 ➔ Jan 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Breast Cancer • Lung Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • HER-2

Phase 1 Study of [177Lu]Lu-NeoB in Patients with Advanced Solid Tumors Overexpressing Gastrin-Releasing Peptide Receptor: Preliminary Safety and Dosimetry Results. (PubMed, J Nucl Med) - " 177Lu-NeoB has a favorable organ dosimetry profile in patients with advanced solid tumors expressing GRPR, with a large safety margin compared with accepted external beam radiation therapy thresholds for organ toxicity. The maximum tolerated dose of 177Lu-NeoB was identified as 9.25 GBq, and the recommended phase 2 dose for the phase 2a dose expansion is 9.25 GBq."

Journal • P1 data • Brain Cancer • Breast Cancer • CNS Disorders • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Glioblastoma • Hematological Disorders • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • GRP-10

Trial in progress: A Phase Ib dose-finding study and evaluation of [177Lu]Lu-NeoB plus radiotherapy and temozolomide for newly diagnosed glioblastoma and as a single agent for recurrent glioblastoma (SNO 2025) - P1 | "The primary endpoint is the incidence and nature of DLTs with the aim to identify the recommended doses of [177Lu]Lu-NeoB for newly diagnosed and recurrent glioblastoma. Secondary endpoints include safety, dosimetry, and pharmacokinetics of [177Lu]Lu-NeoB (in combination and as a single agent), progression-free survival (modified RANO criteria), and overall survival."

P1 data • Brain Cancer • Glioblastoma • Solid Tumor • GRP-10

Trial in progress: A Phase Ib dose-finding study and evaluation of [177Lu]Lu-NeoB plus radiotherapy and temozolomide for newly diagnosed glioblastoma and as a single agent for recurrent glioblastoma (WFNOS 2025) - P1 | "The primary endpoint is the incidence and nature of DLTs with the aim to identify the recommended doses of [177Lu]Lu-NeoB for newly diagnosed and recurrent glioblastoma. Secondary endpoints include safety, dosimetry, and pharmacokinetics of [177Lu]Lu-NeoB (in combination and as a single agent), progression-free survival (modified RANO criteria), and overall survival."

P1 data • Brain Cancer • Glioblastoma • Oncology • Solid Tumor • GRP-10

In vivo gastrin releasing peptide receptor expression in SDH deficient wild-type gastrointestinal stromal tumours (GIST): potential for theranostic applications. (PubMed, EJNMMI Res) - "The majority of wtGIST patients in this small cohort show lesions with intense [68Ga]NeoB uptake. Heterogeneity of uptake indicates GRPR has highly variable inter- and intralesional expression. NeoB has potential for theranostic application in wtGIST, with limited effective standard of care treatments available. Ongoing trials are investigating the therapeutic use of [177Lu]NeoB in this setting."

Journal • Preclinical • Gastrointestinal Cancer • Oncology • Sarcoma • GRP-10

Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Novartis Pharmaceuticals | Trial completion date: Aug 2031 ➔ Jul 2032 | Trial primary completion date: Feb 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Brain Cancer • Glioblastoma • Oncology • Solid Tumor

First Steps Towards Developing a Dual-Targeted Radionuclide Theranostic Strategy Combining PSMA- and GRPR-Targeting radiopharmaceuticals for Prostate Cancer Management. (EANM 2025) - "Uptake was expressed as percentage added dose / 150.000 cells (%AD/150.000 cells) and normalized to the control (incubation with only [ 161 Tb]Tb-PSMA-I&T or [ 177 Lu]Lu-NeoB)...So far, consecutive and simultaneous incubation of radiolabelled PSMA I&T and radiolabelled NeoB in PC3-PIP cells did not influence uptake of either radiopharmaceutical. Future studies include selecting complementary radionuclides for both PSMA-I&T and NeoB, as well as assessing the therapeutic effect of combined PSMA/GRPR-TRT, with the ultimate aim to develop an effective dual-targeted theranostic strategy for PCa."

Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • FOLH1 • GRP-10

Chemotherapy alters radiosensitivity and GRPR expression of prostate and breast cancer cells. (PubMed, EJNMMI Res) - "Our data demonstrated that chemotherapy alters mechanisms relevant for the success of GRPR-mediated radionuclide therapy in PCa and BC cells in-vitro. These finding were less prominent in-vivo and additional studies are needed to unravel this."

Journal • Breast Cancer • Genito-urinary Cancer • Oncology • Prostate Cancer • Solid Tumor • GRP-10

Phase 1/2 Study of the Novel Radioligand Therapy [177Lu] Lu-NeoB Plus Capecitabine in Patients With ER+/HER2− Advanced Breast Cancer (ABC) With GRPR Expression After Progression on Prior Endocrine Therapy Plus a CDK4/6 Inhibitor for ABC (MBCC 2025) - P1/2 | "For patients with HER2-low disease, prior treatment with trastuzumab deruxtecan is allowed. In phase 1, patients will receive 177Lu-NeoB at 150 millicurie (mCi) every 6 weeks (Q6W) plus capecitabine (1000 mg/m2 by mouth for 14 days, followed by 7 days off)...Enrollment is currently open. Status Currently enrolling."

Clinical • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • ER • HER-2

Phase Ib Dose-Finding Study of [177Lu]Lu-NeoB + Ribociclib + Fulvestrant in Patients With ER+/ HER2− Advanced Breast Cancer With GRPR Expression With Early Relapse FromAdjuvant Endocrine Therapy or Progression on ET + CDK4/6i for ABC (MBCC 2025) - P1 | "Planned enrollment is about 48 patients and is currently open. Status Currently enrolling."

Clinical • Metastases • P1 data • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • CDK4 • ER • HER-2