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Neuroendocrine Tumors

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Adenoma, Islet Cell

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Neuroectodermal Tumors, Primitive

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Gastrointestinal Diseases

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Endocrine System Diseases

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Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Hematinics

All Drugs and Chemicals

Gastrointestinal Agents

Liver Extracts

Lutetium Lu 177 dotatate

Pancrelipase

Pancreatin

Radiopharmaceuticals

Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Participants in this arm will not receive peptide receptor radionuclide therapy (PRRT).

Arm 2 will undergo four cycles of peptide receptor radionuclide therapy (PRRT) before cytoreductive surgery.

Cytoreductive surgery is an operation to remove as much tumor tissue as possible.

cytoreductive surgery

PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera). Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through blood.

Lutathera - a small molecule used in Peptide Receptor Radionuclide Therapy (PRRT)

PRRT is a molecular targeted therapy used to treat neuroendocrine tumors (NET). Molecular targeted therapies use drugs or other substances to identify and attack cancer cells while reducing harm to healthy tissue. PRRT delivers high doses of radiation to tumors in the body to destroy or slow their growth and reduce disease side effects.

Peptide receptor radionuclide therapy (PRRT)

Xavier Keutgen, MD

Cancer Clinical Trials Office

Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental.

Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.

Doctors and researchers leading this study hope to learn more about peptide receptor radionuclide therapy (PRRT) in combination with cytoreduction (surgically removing tumors). They hope to learn if combining PRRT in combination with cytoreduction would be more effective than cytoreduction alone. PRRT itself is approved by the U.S. Food and Drug Administration (FDA) for people with PanNETs however the combination with cytoreduction is considered experimental.

Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.

PRRT is a form of targeted treatment (think of a "lock and key") done by the use of a small molecule (Lutathera) Lutathera acts as a "key" to "lock" onto certain areas your tumor cells called receptors when injected into a vein and travels through the bloodstream. Lutetium-177 is the radionuclide in Lutathera which is a chemical that delivers strong radiation directly into your tumor cells and works by causing death of the cancerous tissues.

PRRT can only be done on patients who have tumors that have the somatostatin receptors. Before being given PRRT, your treating doctor will run imaging tests to make sure your tumors have these targeted receptors. Your participation in this research will last about 2 years. The purpose of this research is to gather information on the safety and effectiveness of PRRT.

Participants will be randomized (like the flip of a coin) to one of two arms. Arm 1 is the control arm, which will undergo standard of care cytoreductive surgery (for the tumor). Arm 2 will undergo four cycles of PRRT before cytoreductive surgery.

Preoperative PRRT Versus Surgical Cytoreduction in Metastatic Pancreatic Neuroendocrine Tumors to the Liver

Preoperative PRRT Versus Surgical Cytoreduction Alone in Metastatic Pancreatic Neuroendocrine Tumors to the Liver: A Phase II Multi-institutional Trial

To determine whether preoperative peptide receptor radionuclide therapy (PRRT) prior to hepatic cytoreduction increases progression free survival (PFS1) (when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver

To determine whether preoperative peptide receptor radionuclide therapy (PRRT) prior to hepatic cytoreduction increases overall survival.

(when compared to cytoreduction alone) in patients with metastatic PanNETs to the liver

To determine whether preoperative peptide receptor radionuclide therapy (PRRT) induces a significant objective response rate (according to RECIST) in the primary tumor (if available) and hepatic metastases of patients with metastatic PanNETs to the liver, thus facilitating surgical resection.

To determine whether PRRT plus cytoreductive surgery increases PFS when compared to a historical cohort of patients undergoing PRRT only for metastatic PanNETs.

To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves progression-free survival (PFS2)

To determine whether PRRT plus cytoreduction compared to cytoreduction alone followed by PRRT once progression has occurred improves Overall Survival.

To determine differences in imaging characteristics (e.g. tumor size), biochemical and molecular signatures of patients having received surgery + PRRT or surgery alone.

University of Chicago

Gastro-enteropancreatic Neuroendocrine Tumor

Pharmaceutical Solutions

Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GBq (200 mCi) (±5%) each, given 12 weeks (±1 week) apart, injected intravenously simultaneously with nephroprotective perfusion of an amino acid solution.

Intravenous injection of 177Lu-octreotate

Patrick Flamen, M.D., Ph.D.

Amélie Deleporte, MD

Alain Hendlisz, MD

Ioannis Karfis, MD

The purpose of this study is to determine if 68Gallium-octreotate and 18Fluorodesoxyglucose uptake, apparent diffusion coefficient and post 177Lu-octreotate SPECT/CT dosimetry are reliable predictors for lesion-by-lesion treatment outcome.

This is a feasibility study evaluating the use of 177Lutetium-octreotate in the treatment of advanced refractory Neuroendocrine Tumors.

Objectives of the study:

1. Primary (on a lesion basis): To assess the value of the following parameters (obtained through functional and molecular imaging) for predicting the lesion-by-lesion PRRT treatment outcome:

   * 18FDG uptake on 18FDG PET/CT
   * 68Ga-octreotate uptake on 68Ga-octreotate PET/CT
   * Apparent diffusion coefficient on diffusion weighted MRI (for these 3 parameters, absolute values at baseline)
   * Tumor dosimetry on post 177Lu-octreotate SPECT/CT after each cycle.
2. Secondary (on a patient basis): To generate a patient-based response model based on the previously defined parameters.
3. Exploratory (on a lesion basis): To assess the value of the parameters mentioned in the primary objective for predicting the lesion-by-lesion PRRT treatment outcome:

   * absolute values of the three imaging parameters and their relative changes after each cycle;
   * serial tumor dosimetry on post-177Lu-octreotate SPECT/CT after each cycle.

Treatment will consist of 177Lu-octreotate injections in fixed activities of 7,4 GigaBecqurel each, given 11-13 weeks apart, injected intravenously with simultaneous infusion of an amino acid solution. (Before amino acid nephroprotection, ondansetron, methylprednisolone and metoclopramid, are given intravenously in order to prevent nausea or vomiting). Approximately 30 min after the beginning of the amino acid solution, 177Lu-octreotate is co-infused over 15-30 minutes. The amino acid infusion is continued at the same rate for 3-5 more hours (total infusion lasts 4-6 hours).

In total, 4 cycles (= injections of 177Lu-octreotate) are planned. However, the total number of administered cycles will be limited by critical organ (kidneys and bone marrow) threshold toxicities.

Treatment efficacy will be assessed:

* on a lesion-basis (change of longest transversal diameter).
* on a patient-basis using Response Evaluation Criteria In Solid Tumors (RECIST) 1.1.

177Lutetium-octreotate Treatment Prediction Using Multimodality Imaging in Refractory NETs

The LuMEn Study: 177Lu-octreotate Treatment Outcome Prediction Using Multimodality Imaging in Refractory Neuroendocrine Tumours.

TTP is defined as the time between treatment initiation and objective tumor progression with censoring of patients who die as a result of any cause.

PFS is defined as the time between treatment initiation and the first of the following events: disease progression (clinical or radiological) or death resulting from any cause.

Jules Bordet Institute

Antineoplastic Agents

Somatostatin

Octreotide

Chelating Agents

Edotreotide

Edotreotide lutetium LU-177

The first test injection will be with 161Tb-DOTA-LM3; the second one will be with 177Lu-DOTATOC. The \~ 3 therapy cycles will be performed with 177Lu-DOTATOC.

Test injection 1: 0.5 - 1 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Test injection 2 (Cross over): 0.5 - 1 GBq \~ 200 μg 177Lu-DOTATOC with renal protection Not more than 6 weeks later patients will receive \~ 3 treatment cycles with 5.6 - 7.4 GBq 177Lu-DOTATOC in an interval of about 8 weeks (clinically established amount of activity). This is standard of care and not part of the study.

The first test injection will be with 177Lu-DOTATOC; the second one will be with 161Tb-DOTA-LM3. The \~ 3 therapy cycles will be performed with 177Lu-DOTATOC.

Test injection 1: Group 2: 0.5 - 1 GBq \~ 200 μg 177Lu-DOTATOC with renal protection Test injection 2 (Cross over): 0.5 - 1 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 3 treatment cycles with 5.6 - 7.4 GBq 177Lu-DOTATOC in an interval of about 8 weeks (clinically established amount of activity). This is standard of care and not part of the study.

Both test injections will be with 161Tb-DOTA-LM3 (with different peptide amounts). The \~ 2 therapy cycles will be performed with 161Tb-DOTA-LM3.

Test injection 1: \~ 2 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Test injection 2: \~ 2 GBq \~ 300 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 2 cycles with \~ 3 GBq 161Tb-DOTA-LM3 in an interval of about 8 weeks if \~2 GBq is well tolerated

Start with the other peptide amount of 161Tb-DOTA-LM3. The \~ 2 therapy cycles will be performed with 161Tb-DOTA-LM3.

Test injection 1: \~ 2 GBq \~ 300 μg 161Tb-DOTA-LM3 with renal protection Test injection 2: \~ 2 GBq ≤ 100 μg 161Tb-DOTA-LM3 with renal protection Not more than 6 weeks later patients will receive \~ 2 cycles with \~ 3 GBq 161Tb-DOTA-LM3 in an interval of about 8 weeks if \~2 GBq is well tolerated

161Tb-DOTA-LM3 is a therapeutic medicinal product with three main components, namely (a) Terbium-161 (161Tb), a beta minus-, gamma- and Auger-/conversion electron-emitting radionuclide with a half-life of 6.96 days; (b) DOTA, a chelator that allows stable complexation of 161Tb; and (c) LM3, an antagonistic SST analogue which binds to SST2 receptors (SST2 receptor antagonist).

All doses are presented as a sterile aqueous solution for i. v. infusion with renal protection.

161Tb-DOTA-LM3

177Lu-DOTATOC = 177Lu-edotreotide is a therapeutic medicinal product with three main components (a) Lutetium-177 (177Lu), a beta minus and gamma--emitting radionuclide with a half-life of 6.65 days; (b) DOTA, a chemical chelator that allows stable complexation of 177Lu; and (c) TOC (= \[Tyr\]3-octreotide) an agonistic somatostatin analogue which binds to SST2 and much less to SST5 receptors (SST2 receptor agonist).

All doses are presented as a sterile aqueous solution for i. v. infusion with renal protection.

177Lu-DOTATOC

Julia Fricke, Dr. med.

Emanuel Christ, Prof. Dr. med.

Damian Wild, Prof. Dr. med.

The goal of this phase 0 proof-of concept study is to measure the therapeutic index (tumour to dose-limiting-organ dose ratios) of 161Tb-DOTA-LM3 in comparison to the current standard 177Lu-DOTATOC in the same gastroenteropancreatic neuroendocrine tumour (GEP-NET) patients in a randomized, cross-over design, in all patients.

Population to be studied are patients with diagnosed and metastasized secreting and non-secreting GEP-NEN (grade 1 and 2). The number of participants will be limited to 4 - 8 patients (phase 0a) and 4 - 8 patients (phase 0b). All patients will get the same treatment in a balanced cross-over order. The study will be divided into a phase 0a and phase 0b. Beforehand the selected patients will be randomised into two groups. In phase 0a one test injection with 161Tb-DOTA-LM3 and 177Lu-DOTATOC will administered in both randomised groups in a different order followed by \~ 3 cycles PRRT with 177Lu-DOTATOC in both groups. In phase 0b two test injections with 161Tb-DOTA-LM3 (with different peptide amounts) will administered in both randomised groups in a different order followed by \~2 cycles PRRT with 161Tb-DOTA-LM3 in both groups.

Neuroendocrine neoplasia's (NENs) are a group of neoplasms arising from neuroendocrine cells and are most commonly found in the intestine, pancreas and lung. The overexpression of somatostatin receptor subtype 2 (SST2), is a characteristic of NENs and presents an important molecular target for the management of these tumours. Peptide receptor radionuclide therapy (PRRT) targets the SST2 through the administration of radiolabelled SST2 agonists such as 177Lu-DOTATOC and 177Lu-DOTATATE (Lutathera®). Although PRRT is one of the most efficient treatments for the management of NENs, it does only stabilize but not cure the disease. There is a need to improve PRRT with more effective radiopharmaceuticals. There is evidence that terbium-161 (161Tb) is more powerful that 177Lu not only in combination with SST2 agonists but particularly with SST2 antagonists.

The efficacy of PRRT can be enhanced by using a potent SST2 antagonist (DOTA-LM3) labelled with 161Tb. 161Tb-DOTA-LM3 has the following advantages compared to 177Lu-DOTATOC and 177Lu-DOTATATE: 1) SST2 antagonists bind to many more SST2-binding sites and accumulate mainly on the cellular membrane. 2) The Auger electrons of 161Tb deposit their high energy over a short distance (1-1000 nm) resulting in a high relative biological effectiveness mainly to the cell membrane which seems to be more radiosensitive than the cytoplasm. 161Tb-DOTA-LM3 does, therefore, not only deliver dose by β- radiation, but also through the emission of conversion and Auger electrons which leads to a 3 - 4 fold increased dose to single cancer cells compared to 177Lu-DOTA-LM3.

The goal of this phase 0 proof-of concept study is to measure the therapeutic index (tumour to dose-limiting-organ dose ratios) of 161Tb-DOTA-LM3 in comparison to the current standard 177Lu-DOTATOC in the same gastroenteropancreatic neuroendocrine tumour (GEP-NET) patients.

A randomized, cross-over, prospective, single-centre, open label phase 0 study, comparing the dosimetry of 177Lu-DOTATOC and 161Tb-DOTA-LM3 in the same patients.

Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)

Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3): Beta Plus Study

Assessment and comparison of the tumour-to-bone marrow dose ratio of 161Tb-DOTA-LM3 vs 177Lu-DOTATOC. In order to get kinetic information of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of abdomen are performed at different time points post injection 161Tb-DOTA-LM3 or 177Lu-DOTATOC: \~ 3, \~ 24, \~ 72 and \~ 168 hours.

Assessment and comparison of the tumour-to-kidney dose ratio of 161Tb-DOTA-LM3 vs 177Lu-DOTATOC. In order to get kinetic information of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for this task total body scintigraphy and SPECT/CT of abdomen are performed at different time points post injection 161Tb-DOTA-LM3 or 177Lu-DOTATOC: \~ 3, \~ 24, \~ 72 and \~ 168 hours.

Assessment of the median tumour dose per GBq injected activity (Median of the mean of 2 - 6 tumours per patient which can be identified with both compounds.). Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at \~ 3, \~ 24, \~ 72 and \~ 168 hours.

Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at \~ 3, \~ 24, \~ 72 and \~ 168 hours.

Assessment of bone marrow toxicity after test injection of 177Lu-DOTATOC and 161Tb-DOTA-LM3 using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Assessment of the median dose per GBq injected activity in other organs than bone marrow and kidneys. Kinetic information of the biodistribution of 161Tb-DOTA-LM3 and 177Lu-DOTATOC for dosimetry calculations will be generated by performing sequential SPECT/CT scans for example at \~ 3, \~ 24, \~ 72 and \~ 168 hours.

Swiss National Science Foundation

Paul Scherrer Institute (PSI)

University Hospital, Basel, Switzerland

Up to 192 participants treated with \[177Lu\]Lu-FAP-2286 in tumor-specific participant groups in monotherapy and in combination with chemotherapy.

68Ga-FAP-2286 IV administered as imaging agent for PET scan.

68Ga-FAP-2286

Phase 1:

Patients with positive uptake of 68Ga-FAP- 2286 will receive a fixed dose of 177Lu-FAP-2286 IV administered every 6 weeks for a maximum of 6 doses. Doses range between 3.7 and 9.25 GBq (100-250 mCi).

Phase 2:

Monotherapy: Patients with positive uptake of 68Ga FAP 2286 will receive a fixed dose of 177Lu FAP 2286 IV administered at the RP2D determined in Phase 1 dose escalation in every 4 weeks.

Combination therapy: Patients with positive uptake of 68Ga FAP 2286 will receive 177Lu-FAP-2286 based on dose escalation (starting with dose level 1) followed by dose expansion at selected dose.

177Lu-FAP-2286

Novartis Pharmaceuticals

Fibroblast activation protein (FAP) is a cell surface protein that is highly expressed on the surface of cancer-associated fibroblasts (CAFs) present in the tumor microenvironment of most epithelial cancers, whereas limited expression of FAP is observed in normal tissues. In some cancers of mesenchymal origin, notably sarcoma and mesothelioma, FAP expression has also been observed on the tumor cells themselves. Given the restricted expression profile, FAP is a promising target for peptide-targeted radionuclide imaging and therapeutic agents.

Phase 1 of this study is designed to evaluate the safety and establish the recommended intravenous (IV) Phase 2 dose (RP2D) for \[177Lu\]Lu FAP 2286 monotherapy in participants with FAP expressing solid tumors.

Phase 2 is designed to evaluate the safety and efficacy of \[177Lu\]Lu FAP 2286 as monotherapy in participants with pancreatic ductal adenocarcinoma (PDAC), non-small cell lung cancer (NSCLC), and breast cancer (BC) and in combination with chemotherapy in participants with untreated PDAC or relapsed NSCLC.

Participants in both Phase 1 and 2 will be selected for treatment with \[177Lu\]Lu FAP 2286 based on \[68Ga\]Ga FAP 2286 imaging for determining tumor FAP expression.

Screening Period:

All participants will undergo screening assessments including disease assessments per CT or MRI per RECIST v1.1 criteria prior to administration of \[68Ga\]Ga FAP 2286. Each participant must provide informed consent and agree to provide an archival tumor tissue sample, if available, and blood samples for biomarker assessment. Participants must meet all entry criteria as specified in the protocol.

In Phase 1 only, participants will also undergo FDG-PET imaging. In the Phase 2 part, \[177Lu\]Lu FAP 2286 will be investigated in monotherapy and in combination with chemotherapy. All participants in the combination group may begin chemotherapy prior to \[177Lu\]Lu FAP 2286.

Participants meeting entry criteria will be enrolled and participants who have not had prior PET/CT imaging with \[68Ga\]Ga FAP 2286 in the previous 3 months (applicable only to Phase 1) will undergo PET imaging with \[68Ga\]Ga FAP prior to initiating treatment with \[177Lu\]Lu FAP 2286. Participants must have a positive \[68Ga\]Ga FAP PET/CT scan, as described in the criteria for continuation to \[177Lu\]Lu FAP 2286 therapy, in order to be treated with \[177Lu\]Lu FAP 2286.

Treatment Period:

A single IV dose of \[177Lu\]Lu FAP 2286 will be initially administered every 6 weeks (window of - 1 to + 7 days) up to a maximum of 6 doses in Phase 1. In Phase 2, \[177Lu\]Lu FAP 2286 will be administered every 4 weeks (28 days ± 3 days).

All participants will be monitored for safety throughout the Treatment Period. All participants will be assessed for disease status per RECIST v1.1 every 6 weeks (42 days). Participants will receive \[177Lu\]Lu FAP 2286 until the maximum doses allowed are administered, confirmed radiographic disease progression assessed by investigator based on RECIST v1.1 criteria, unequivocal clinical disease progression, unacceptable toxicity or inability to tolerate further treatment, loss to follow-up, or withdrawal of consent.

Safety data will be periodically reviewed by the DCRC during dose escalation and by a Data Monitoring Committee (DMC) during dose expansion.

End of Treatment (EOT) Visit:

In Phase 1, participants will have an EOT Visit 6 to 8 weeks after the last dose of \[177Lu\]Lu FAP 2286 except in cases of participant death, loss to follow up, or withdrawal of consent for further follow up. Participants in Phase 2 will have an EOT visit within 28 days from the last dose of study treatment except in case of participant death, loss to follow-up, or withdrawal of consent for further follow-up.

Post treatment safety follow-up:

In Phase 2, after discontinuation of study treatment for any reason, all participants will have safety follow-up for 6 weeks (+/- 1 week) after their last study treatment administration, except in case of death, loss to follow-up or withdrawal of consent as per the schedule of assessments.

Long-term Follow-up (LFTU) Period:

Upon completion of the EOT Visit, participants will enter the LTFU Period. The LTFU Period will include safety, disease, and survival assessments, as applicable.

* Safety assessments will be performed every 12 weeks (+/- 1 week) for 2 years, then every 6 months until 5 years.
* Disease assessments will be performed for all participants who complete the EOT for a reason other than radiographic disease progression. Participants should continue to have tumor scans performed until radiographic disease progression, death, loss to follow-up, withdrawal from study, study closure or initiation of subsequent anticancer treatment.
* Survival assessments will be performed for all participants.

A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE)

LuMIERE: A Phase 1/2, Multicenter, Open-label, Non-randomized Study to Investigate Safety and Tolerability, Pharmacokinetics, Dosimetry, and Preliminary Activity of 177Lu-FAP-2286 in Patients With an Advanced Solid Tumor

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D

Objective response is defined as a best confirmed response of CR or PR by RECIST v1.1 as assessed by the investigator. A confirmed CR or PR is a response that is maintained and documented on a subsequent tumor assessment no less than 28 days after the initial response. For Phase 2, ORR defined as the frequency and percentage of participants with a best confirmed response of CR or PR will be analyzed.

To evaluate the safety and tolerability of \[177Lu\]Lu FAP 2286 and determine the RP2D in combination with mFOLFIRNOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC (Phase 2 dose escalation for combination therapy)

To measure the radiation dosimetry of \[177Lu\]Lu FAP 2286

To determine tumor uptake using \[68Ga\]Ga FAP 2286

To evaluate tumor uptake of \[68Ga\]Ga FAP 2286 as compared to FDG

To evaluate the PK of \[177Lu\]Lu FAP 2286

Objective response is defined as a best confirmed response of CR or PR by RECIST v1.1 as assessed by the investigator. A confirmed CR or PR is a response that is maintained and documented on a subsequent tumor assessment no less than 28 days after the initial response.

To evaluate the safety and tolerability of \[68Ga\]Ga FAP 2286.

Duration of Response (DOR) was defined as the duration between the date of first documented Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) and the date of first documented radiographic progression or death due to any cause as assessed by investigator according to RECIST v1.1.

Disease Control Rate (DCR) is defined as the frequency and percentage of participants with stable disease (SD) of at least 12 weeks (2 consecutive scans with Best Overall Response (BOR) of SD) or a best confirmed response of CR or PR.

Progression-free survival (PFS) is defined as the time from the date of randomization to the date of first evidence of radiographic progression or death due to any cause, whichever occurred first.

The distribution of adverse events of \[177Lu\]Lu FAP 2286 at the RP2D for monotherapy, the RP2D in combination with mFOLFIRNOX in PDAC and the RP2D in combination with nab-paclitaxel in NSCLC 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.

The distribution of adverse events for \[68Ga\]Ga FAP 2286 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.

Mouth and Tooth Diseases

Ear, Nose, and Throat Diseases

Carcinoma

Nasopharyngeal Carcinoma

Nasopharyngeal Neoplasms

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Head and Neck Neoplasms

Nasopharyngeal Diseases

Pharyngeal Diseases

Stomatognathic Diseases

Otorhinolaryngologic Diseases

Treatment with 177Lu-DOTATATE consist of a cumulative dose of 23.68 - 29.6 GBq (640 - 800 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Four administrations of 5.92 - 7.4 GBq (160 - 200 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Concomitant amino acids will be given with each administration for kidney protection; 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity.

Treatment will consist of a cumulative dose of 23.68 - 29.6 GBq (640 - 800 mCi) 177Lu-DOTA0 -Tyr3-Octreotate; Four administrations of 5.92 - 7.4 GBq (160 - 200 mCi) 177Lu-DOTA0-Tyr3-Octreotate; Concomitant amino acids will be given with each administration for kidney protection; 177Lu-DOTA0-Tyr3-Octreotate will be administered at 8±1-week intervals, which can be extended up to 16 weeks to accommodate resolving acute toxicity.

77 Lu-DOTA0-Tyr3-Octreotate

Daniel Tan, BSc, MBBS, PhD

Wen-Long Nei

Wen-Long Nei, MBBS, FRCR

Kelvin Loke, MBBS, MRCP(UK), FAMS

This study is the first phase II study of 177Lu-DOTA0-Tyr3-Octreotate in metastatic NPC. Patients whom have failed 2 or more lines of therapy or exhausted standard therapy and are avid on 68Ga-DOTATATE imaging will be eligible to receive up to 4 cycles of 177Lu-DOTA0-Tyr3-Octreotate. The primary outcome will be progression free survival at 6 months.

This would be an open label, single arm, single centre, phase II study designed to evaluate the efficacy of 177Lu-DOTA0-Tyr3-Octreotate in Metastatic NPC.

Patients will first need to go for a 68Ga-DOTATATE scan to determine if they are suitable for 177Lu-DOTA0-Tyr3-Octreotate therapy. A'Hern single stage phase II design (A'Hern, 2001) will be used for conducting the trial. The null hypothesis that the true PFS rate at 6 months is 10% will be tested against the alternate hypothesis of 25%. A total number of 25 patients will be recruited. If there are 5 or more patients who are alive and progression free among these 25 patients at 6 months, we reject the null hypothesis and claim that the treatment is promising.

The design controls the type I error rate at 9.8% and yields a power of 78.6% when the true PFS rate at 6 months is 25%. The first 5 patients will receive 180mCi of 177Lu-DOTA0-Tyr3-Octreotate for the first cycle followed by 200mCi for the remaining 3 cycles if there are no \> Grade 2 toxicities after the first cycle. If there are \>G2 toxicities, the remaining cycles will proceed at 180mCi. A safety review will be done after the first 5 patients. If there are no significant toxicities, the remaining patients will receive 200mCi for 4 cycles. If there are significant toxicities in patients receiving 200mCi for the 2nd to 4th cycle, the remaining patients will receive 180mCi for 4 cycles. If there are significant toxicities in patients receiving 180mCi for the 2nd to 4th cycle, the remaining patients will receive 160mCi for 4 cycles. Dosimetry scans will be done after each cycle of 177Lu-DOTA0-Tyr3-Octreotate at 1h and 96h. Safety and tolerability of 177LuDOTA0-Tyr3-Octreotate will be assessed for the duration of study treatment.

FDG PET/CT scan and 68Ga-DOTATATE scan will be performed at baseline and after cycle 1 (week 4) and cycle 4 (week 28). CT scans will be done at week 12, 24, then 3-monthly starting from week 40. 177Lu-DOTA0-Tyr3-Octreotate treatment will be continued until progression of disease, unacceptable toxicity, or another discontinuation criterion is met. In the case of toxicity, dose adjustment is permitted. A treatment cycle is eight weeks (56 days) and will be repeated without therapy interruption for 4 cycles unless there is dose limiting toxicities.

Phase II 177Lu-DOTATATE Study in Metastatic NPC With a Safety Run-in

A Biomarker Enrichment, Phase II Study of 177Lu-DOTATATE in Metastatic Nasopharyngeal Cancer With a Safety Run-in

PFS is defined as the time from the date of initiating study treatment to the date of documented disease progression as determined by RECIST Criteria, Version 1.1 or death from any cause.

Point estimates for median PFS and PFS rate at 6 month, with corresponding 95% Confidence Intervals (CIs), will be estimated using the Kaplan-Meier method.

ORR is defined as the percentage of patients who had a partial response or complete response according to RECIST 1.1.

The ORR and 95% CI will be calculated.

TTP is defined as the time (number of days) from start of study treatment to objective tumour progression.

OS is defined as the time from the date of start of study treatment to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Preoperative PRRT Versus Surgical Cytoreduction in Metastatic Pancreatic Neuroendocrine Tumors to the Liver	NCT05610826	Pancreatic Neur... Pancreas Cancer	cytoreductive s... Lutathera - a s... Peptide recepto...	18 Years -	University of Chicago
177Lutetium-octreotate Treatment Prediction Using Multimodality Imaging in Refractory NETs	NCT01842165	Gastroenteropan...	Intravenous inj...	18 Years -	Jules Bordet Institute
Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)	NCT05359146	Neuroendocrine ... Gastroenteropan...	161Tb-DOTA-LM3 177Lu-DOTATOC	18 Years -	University Hospital, Basel, Switzerland
Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)	NCT05359146	Neuroendocrine ... Gastroenteropan...	161Tb-DOTA-LM3 177Lu-DOTATOC	18 Years -	University Hospital, Basel, Switzerland
A Study of 177Lu-FAP-2286 in Advanced Solid Tumors (LuMIERE)	NCT04939610	Solid Tumor	68Ga-FAP-2286 177Lu-FAP-2286	18 Years -	Novartis
Combined Beta- Plus Auger Electron Therapy Using a Novel Somatostatin Receptor Subtype 2 Antagonist Labelled With Terbium-161 (161Tb-DOTA-LM3)	NCT05359146	Neuroendocrine ... Gastroenteropan...	161Tb-DOTA-LM3 177Lu-DOTATOC	18 Years -	University Hospital, Basel, Switzerland
Phase II 177Lu-DOTATATE Study in Metastatic NPC With a Safety Run-in	NCT05198479	Metastatic Naso...	77 Lu-DOTA0-Tyr...	21 Years - 75 Years	National Cancer Centre, Singapore

Spots Global Cancer Trial Database for peptide receptor radionuclide therapy (prrt)