AAA603 / Novartis - LARVOL DELTA

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

NeoRay: [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake (clinicaltrials.gov) - P1/2 | N=51 | Active, not recruiting | Sponsor: Advanced Accelerator Applications | Recruiting ➔ Active, not recruiting

Enrollment closed • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • HER-2

Phase I/II study of the novel radioligand therapy [177Lu]Lu-NeoB plus capecitabine in patients w/ ER+/HER2- advanced breast cancer (ABC) w/GRPR expression after progression on prior endocrine therapy (ET) plus a CDK4/6 inhibitor (CDK4/6i) for ABC (SABCS 2024) - P1/2 | "For patients with HER2-low disease, prior treatment with trastuzumab deruxtecan is allowed. Planned enrollment is approximately 58 patients across both phases. Patient enrollment is currently open."

Clinical • Metastases • P1/2 data • Breast Cancer • Estrogen Receptor Positive Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Breast Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • ER • HER-2

Phase Ib dose-finding study of [177Lu]Lu-NeoB + ribociclib + fulvestrant in patients w/ ER+/HER2- advanced breast cancer (ABC) w/ GRPR expression w/ early relapse from (neo)adjuvant endocrine therapy (ET) or progression on ET + CDK4/6i for ABC (SABCS 2024) - P1 | "Pre/perimenopausal pts will also receive goserelin (3.6 mg on d1 of a 28-d cycle). Pt enrollment is currently open. Clinical trial ID: NCT05870579."

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

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: Jun 2026 ➔ Aug 2031

Combination therapy • Trial completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

Comparative Evaluation of [161Tb]Tb-NeoB and [177Lu] Lu-NeoB for GRPR-mediated Targeted Radionuclide Therapy (EANM 2024) - "Our studies demonstrate that the binding affinity and specific cellular uptake of [161Tb]Tb-NeoB is slightly lower but still within the same range as that of [177Lu]Lu-NeoB. We have previously observed similar slightly lower specific uptake of terbium-161 labelled compounds directed to different targets, with a yet unknown underlying cause. Further assessment of the cytotoxic effects of [161Tb]Tb-NeoB in comparison to [177Lu]Lu-NeoB are currently ongoing."

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

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=36 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • Solid Tumor

[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 | Trial primary completion date: Dec 2031 ➔ Dec 2026

Combination therapy • Metastases • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

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=58 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor

[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 | Trial completion date: Jan 2030 ➔ Dec 2031 | Trial primary completion date: Jan 2030 ➔ Dec 2031

Combination therapy • Metastases • Trial completion date • Trial primary completion date • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor • ER • HER-2

Gallium-68-NeoB PET in Breast Cancer Patients: First results from a Prospective Observational Trial (SNMMI 2024) - "Patients with ER+/HER2- breast cancer showed the highest rate of NeoB-positive disease. In these patients, global uptake was larger than liver uptake in about 2/3 of patients with 1/3 of patients showing global high or very high uptake. Future evaluations are warranted to identify candidates for 177Lu-NeoB radionuclide therapy in a theranostic approach."

Clinical • Observational data • Breast Cancer • Hepatology • HER2 Breast Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • ER • GRP-10 • HER-2

NeoRay: [177Lu]-NeoB in Patients With Advanced Solid Tumors and With [68Ga]-NeoB Lesion Uptake (clinicaltrials.gov) - P1/2 | N=51 | Recruiting | Sponsor: Advanced Accelerator Applications | N=86 ➔ 51 | Trial completion date: Oct 2025 ➔ Dec 2026

Enrollment change • Metastases • Trial completion date • Breast Cancer • HER2 Breast Cancer • Hormone Receptor Breast Cancer • Lung Cancer • Oncology • Solid Tumor • BRCA1 • BRCA2 • CDK4 • HER-2

Dose Finding Study of [177Lu]Lu-NeoB in Newly Diagnosed Glioblastoma and in Recurrent Glioblastoma (clinicaltrials.gov) - P1 | N=48 | Recruiting | Sponsor: Novartis Pharmaceuticals | Not yet recruiting ➔ Recruiting | Trial completion date: Nov 2025 ➔ Jun 2026 | Trial primary completion date: Oct 2025 ➔ May 2026

Combination therapy • Enrollment open • Trial completion date • Trial primary completion date • Brain Cancer • CNS Tumor • Glioblastoma • Oncology • Solid Tumor

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=36 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

Metastases • New P1 trial • Genito-urinary Cancer • Neuroendocrine Tumor • Oncology • Prostate Cancer • 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 • Metastases • Brain Cancer • Breast Cancer • CNS Tumor • Gastrointestinal Cancer • Gastrointestinal Stromal Tumor • Genito-urinary Cancer • Glioblastoma • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Prostate Cancer • Sarcoma • Solid Tumor • GRP-10 • HER-2

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=58 | Not yet recruiting | Sponsor: Novartis Pharmaceuticals

New P1/2 trial • Breast Cancer • HER2 Breast Cancer • HER2 Negative Breast Cancer • Hormone Receptor Breast Cancer • Hormone Receptor Positive Breast Cancer • Oncology • Solid Tumor