Study of RYZ101 Compared With SOC in Pts w Inoperable SSTR+ Well-differentiated GEP-NET That Has Progressed Following 177Lu-SSA Therapy

Summary

This study aims to determine the safety, pharmacokinetics (PK) and recommended Phase 3 dose (RP3D) of RYZ101 in Part 1, and the safety, efficacy, and PK of RYZ101 compared with investigator-selected standard of care (SoC) therapy in Part 2 in subjects with inoperable, advanced, well-differentiated, somatostatin receptor expressing (SSTR+) gastroenteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following treatment with Lutetium 177-labelled somatostatin analogue (177Lu-SSA) therapy, such as 177Lu-DOTATATE or 177Lu-DOTATOC (177Lu-DOTATATE/TOC), or 177Lu-high affinity \[HA\]-DOTATATE.

Interventions

• RYZ101 · DRUG

  RP3D as determined in Phase 1b

• Everolimus · DRUG

  Everolimus

• Sunitinib · DRUG

  Sunitinib

• Octreotide · DRUG

  High-dose octreotide

• Lanreotide · DRUG

  Lanreotide

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Inclusion:

* Histologically proven, Grade 1-2 well differentiated, inoperable, advanced GEP-NETs (Ki67 ≤20%) Eastern Cooperative Oncology Group (ECOG) status 0-2. Ki67% \<20% is not required for the ad hoc subcohort of the PK/ECG substudy.
* Progressive, SSTR-PET positive (i.e., Krenning score 3 or 4) GEP-NET (GI or pancreas) following 2-4 cycles of treatment with 177Lu-labeled SSA. Must have achieved disease control for at least 6 months following Lu-177 SSA (archival tissue is not required for the ad hoc subcohort of the PK/ECG substudy). No time limit is defined between 177Lu-SSA treatment and randomization. There must be at least 1 SSTR-PET imaging-positive measurable site of disease (according to RECIST v1.1) and no RECIST v1.1 measurable metastatic lesions that are SSTR imaging-negative.
* Adequate renal function, as evidenced by estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 (calculated using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\]) (Levey et al. 2009)
* Adequate hematologic function, defined by the following laboratory results:
* Part 2: Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); ANC ≥1000 cells/µL (≥1000 cells/mm3); platelets ≥75 x 109/L (75 x 103/mm3).
* Total bilirubin ≤3 x upper limit normal (ULN)
* Serum albumin ≥3.0 g/dL unless prothrombin time is within the normal range

Exclusion:

* Prior radioembolization
* Significant cardiovascular disease, such as New York Heart Association (NYHA) Class ≥II heart failure, left ventricular ejection fraction (LVEF) \<40% or QT interval corrected for heart rate using Fridericia's formula (QTcF) \>450 ms for males and \>470 ms for females.
* Resistant hypertension, defined as uncontrolled blood pressure (BP) \>140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic (Whelton et al. 2018)
* Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8%
* PRRT other than Lu-177 SSA (not applicable for ad hoc subcohort of the PK/ECG substudy)
* Any condition requiring systemic treatment with high-dose glucocorticoids within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study. Inhaled or topical steroids are permitted.
* Prior history of liver cirrhosis or liver transplantation

Sites (54)

• Research Facility, Phoenix, Arizona · ACTIVE_NOT_RECRUITING
• Research Facility, Duarte, California · COMPLETED
• Research Facility, Irvine, California · RECRUITING
• Research Facility, Los Angeles, California · ACTIVE_NOT_RECRUITING
• Research Facility, Palo Alto, California · ACTIVE_NOT_RECRUITING
• Research Facility, San Francisco, California · ACTIVE_NOT_RECRUITING
• Research Facility, New Haven, Connecticut · ACTIVE_NOT_RECRUITING
• Research Facility, Washington D.C., District of Columbia · ACTIVE_NOT_RECRUITING
• Research Facility, Jacksonville, Florida · ACTIVE_NOT_RECRUITING
• Research Facility, Miami, Florida · RECRUITING
• Research Facility, Tampa, Florida · RECRUITING
• Research Facility, Atlanta, Georgia · ACTIVE_NOT_RECRUITING
• Research Facility, Iowa City, Iowa · RECRUITING
• Research Facility, Lexington, Kentucky · RECRUITING
• Research Facility, Glen Burnie, Maryland · RECRUITING
• Research Facility, Boston, Massachusetts · ACTIVE_NOT_RECRUITING
• Research Facility, Boston, Massachusetts · ACTIVE_NOT_RECRUITING
• Research Facility, Troy, Michigan · COMPLETED
• Research Facility, Rochester, Minnesota · ACTIVE_NOT_RECRUITING
• Research Facility, St Louis, Missouri · RECRUITING
• Research Facility, Omaha, Nebraska · RECRUITING
• Research Facility, New York, New York · ACTIVE_NOT_RECRUITING
• Research Facility, New York, New York · RECRUITING
• Research Facility, Cleveland, Ohio · ACTIVE_NOT_RECRUITING
• Research Facility, Columbus, Ohio · RECRUITING
• Research Facility, Portland, Oregon · ACTIVE_NOT_RECRUITING
• Research Facility, Philadelphia, Pennsylvania · ACTIVE_NOT_RECRUITING
• Research Facility, Pittsburgh, Pennsylvania · RECRUITING
• Research Facility, Nashville, Tennessee · ACTIVE_NOT_RECRUITING
• Research Facility, Houston, Texas · ACTIVE_NOT_RECRUITING
• Research Facility, Salt Lake City, Utah · RECRUITING
• Research Facility, Seattle, Washington · RECRUITING
• Research Facility, Brussels, Belgium · RECRUITING
• Research Facility, Leuven, Belgium · ACTIVE_NOT_RECRUITING
• Research Facility, Roeselare, Belgium · ACTIVE_NOT_RECRUITING
• Research Facility, Brasília, Brazil · ACTIVE_NOT_RECRUITING
• Research Facility, Rio de Janeiro, Brazil · COMPLETED
• Research Facility, São Paulo, Brazil · ACTIVE_NOT_RECRUITING
• Research Facility, London, Ontario, Canada · ACTIVE_NOT_RECRUITING
• Research Facility, Toronto, Ontario, Canada · ACTIVE_NOT_RECRUITING
• Research Facility, Montreal, Quebec, Canada · ACTIVE_NOT_RECRUITING
• Research Facility, Clichy, France · RECRUITING
• Research Facility, Lille, France · RECRUITING
• Research Facility, Montpellier, France · ACTIVE_NOT_RECRUITING
• Research Facility, Nantes, France · ACTIVE_NOT_RECRUITING
• Research Facility, Vandœuvre-lès-Nancy, France · RECRUITING
• Research Facility, Villejuif, France · ACTIVE_NOT_RECRUITING
• Research Facility, Amsterdam, Netherlands · RECRUITING
• Research Facility, Maastricht, Netherlands · ACTIVE_NOT_RECRUITING
• Research Facility, Utrecht, Netherlands · RECRUITING
• Research Facility, Seoul, South Korea · ACTIVE_NOT_RECRUITING
• Research Facility, Barcelona, Spain · RECRUITING
• Research Facility, Madrid, Spain · RECRUITING
• Research Facility, Zaragoza, Spain · COMPLETED