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Phase 1b/3 global, randomized, controlled, open-label trial comparing treatment with RYZ101 to standard of care (SoC) therapy in subjects with inoperable, advanced, somatostatin receptor expressing (SSTR+), well-differentiated gastro-enteropancreatic neuroendocrine tumors (GEP-NETs) that have progressed following prior 177Lu-labelled somatostatin analogue (177Lu-SSA) therapy (ACTION-1)
EU CTIS ID: 2023-509334-19-00
What this study is testing
Part 1: - To determine the RP3D of RYZ101 - To assess the safety and tolerability of RYZ101 in subjects with SSTR+ GEP-NET that has progressed following treatment with 177Lu-SSA Part 2: - To determine if treatment with RYZ101, compared to SoC therapy, improves centrally confirmed PFS in study subjects.
- Therapeutic confirmatory (Phase III)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- Part 2: Subject is a candidate for therapy with 1 of the following SoC options: a. Everolimus 10 mg daily by mouth b. Sunitinib 37.5 mg daily by mouth c. High-dose octreotide LAR 60 mg Q4W by intramuscular (i.m.) injection d. High dose frequency lanreotide 120 mg every 2 weeks (Q2W) by deep subcutaneous (s.c.) injection.
- Adequate renal function, as evidenced by eGFR ≥60 mL/min (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) (Levey et al. 2009) multiplied by individual subject’s BSA and divided by 1.73 m2 (KDIGO 2024 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease) (refer to Appendix 7) )
- 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 >100x 109/L (100 x 103/mm3).
- Total bilirubin ≤3 x upper limit normal (ULN)
- Serum albumin ≥3.0 g/dL unless prothrombin time (PT) is within the normal range
- For women of childbearing potential (WOCBP): a. Negative serum pregnancy test within 48 hours prior to the first dose of study treatment b. Agreement to use barrier contraception and a second form of highly effective contraception while receiving study treatment and for 7 months following their last dose of study treatment. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. c. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study treatment).
You likely can't join if
- Subjects with a GEP-NET deemed nonresponsive to PRRT, defined as no disease control (PR, CR, or SD) achieved for at least 6 months following the last dose of prior 177Lu-DOTATATE/TOC or 177Lu-HA- DOTATATE treatment.
- PRRT other than 177Lu-DOTATATE/TOC or 177Lu-HA-DOTATATE as described in Inclusion Criterion #7
- Any condition requiring systemic treatment with high-dose glucocorticoids (≥20 mg prednisone per day or equivalent) within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study (unless solely for the purpose of adrenal replacement). Inhaled or topical steroids and single dose of steroids as pre-medication for CT scans with contrast are permitted.
- Known hypersensitivity to 225Actinium, 68Gallium, 64Copper, octreotate, or any of the excipients of DOTATATE imaging agents
- Prior history of liver cirrhosis or liver transplantation.
- Part 1: Prior treatment with alkylating agents
See the full eligibility criteria
Who can join
- Part 2: Subject is a candidate for therapy with 1 of the following SoC options: a. Everolimus 10 mg daily by mouth b. Sunitinib 37.5 mg daily by mouth c. High-dose octreotide LAR 60 mg Q4W by intramuscular (i.m.) injection d. High dose frequency lanreotide 120 mg every 2 weeks (Q2W) by deep subcutaneous (s.c.) injection.
- Adequate renal function, as evidenced by eGFR ≥60 mL/min (calculated using the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] equation) (Levey et al. 2009) multiplied by individual subject’s BSA and divided by 1.73 m2 (KDIGO 2024 Clinical Practice Guidelines for the Evaluation and Management of Chronic Kidney Disease) (refer to Appendix 7) )
- 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 >100x 109/L (100 x 103/mm3).
- Total bilirubin ≤3 x upper limit normal (ULN)
- Serum albumin ≥3.0 g/dL unless prothrombin time (PT) is within the normal range
- For women of childbearing potential (WOCBP): a. Negative serum pregnancy test within 48 hours prior to the first dose of study treatment b. Agreement to use barrier contraception and a second form of highly effective contraception while receiving study treatment and for 7 months following their last dose of study treatment. Alternatively, total abstinence is also considered a highly effective contraception method when this is in line with the preferred and usual lifestyle of the subject. c. A woman is considered to be of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (total hysterectomy, or bilateral tubal ligation or bilateral oophorectomy at least 6 weeks before taking study treatment).
- Sexually active male subjects must use a condom during intercourse while receiving study treatment and for 4 months after the last dose of the study treatment and should not father a child during this period. a. Male study participants whose sexual partners are WOCBP must also agree to use a second form of highly effective contraception while receiving study treatment and for 4 months following their last dose of RYZ101. Alternatively, total abstinence is also considered a highly effective contraception method. b. A condom is required to be used also by vasectomized men as well as during intercourse with a male partner to prevent delivery of the drug via seminal fluid.
What rules you out
- Subjects with a GEP-NET deemed nonresponsive to PRRT, defined as no disease control (PR, CR, or SD) achieved for at least 6 months following the last dose of prior 177Lu-DOTATATE/TOC or 177Lu-HA- DOTATATE treatment.
- PRRT other than 177Lu-DOTATATE/TOC or 177Lu-HA-DOTATATE as described in Inclusion Criterion #7
- Any condition requiring systemic treatment with high-dose glucocorticoids (≥20 mg prednisone per day or equivalent) within 14 days prior to first dose of study treatment and/or which cannot be stopped while on study (unless solely for the purpose of adrenal replacement). Inhaled or topical steroids and single dose of steroids as pre-medication for CT scans with contrast are permitted.
- Known hypersensitivity to 225Actinium, 68Gallium, 64Copper, octreotate, or any of the excipients of DOTATATE imaging agents
- Prior history of liver cirrhosis or liver transplantation.
- Part 1: Prior treatment with alkylating agents
- Prior radioembolization
- Any surgery, chemoembolization, and radiofrequency ablation within 12 weeks prior to first dose of study treatment
- Use of anticancer agents within the following intervals prior to the first dose of study treatment: a. PRRT: within < 6 months (177Lu-DOTATATE/TOC or 177Lu-HA- DOTATATE only, as described in Inclusion Criterion #7) b. Chemotherapy: within <6 weeks c. Small molecule inhibitors: within <4 weeks d. Biological agents: within 4 weeks
- Prior radiation therapy as defined below: a. Part 1: Any prior external beam radiation therapy, including stereotactic body radiation therapy (SBRT) b. Part 2: Any of the following: i. Radiation therapy within 6 weeks prior to the first dose of study treatment ii. Prior external beam radiation therapy to more than 25% of the bone marrow
- Prior participation in any interventional clinical study within 30 days prior to first dose of study treatment
- Significant cardiovascular disease, such as New York Heart Association (NYHA) Class ≥II heart failure a. Subjects with a known left ventricular ejection fraction (LVEF) <40% will be excluded. b. Subjects with known coronary artery disease, congestive heart failure not meeting the above criteria, or LVEF <50% must be on a stable medical regimen that is optimized in the opinion of the treating physician. c. QT interval corrected for heart rate using Fridericia's formula (QTcF) >470 ms for females and >450 ms for males, demonstrated by the average value of 3 consecutive ECGs
- Current somatic or psychiatric disease/condition that may interfere with the objectives and assessments of the study
- Pregnancy or breastfeeding
- Resistant hypertension, defined as persistent uncontrolled blood pressure (BP) >140/90 mmHg while on optimal doses of at least 3 antihypertensive medications with 1 being a diuretic. Patients with baseline hypertension may be eligible after initiation of antihypertensive therapy.
- Uncontrolled diabetes mellitus as defined by hemoglobin A1C (HgB A1C) ≥8%
- Have a history of primary malignancy within the past 3 years other than (1) GEP-NET, (2) adequately treated carcinoma in situ or non-melanoma carcinoma of the skin, (3) any other curatively treated malignancy that is not expected to require treatment for recurrence during participation in the study, or (4) an untreated cancer on active surveillance that may not affect the subject's survival status for ≥3 years based on clinician assessment/statement and with Medical Monitor approval.
- Known brain, meningeal or spinal cord metastases. In Part 2, subjects with previously treated brain metastases will be allowed if the following conditions are met: (a) there is no evidence of central nervous system (CNS) progression for at least 6 months as assessed by local MRI for brain metastasis during screening; (b) the subject has recovered from acute side effects of radiotherapy; and (c) the subject is receiving a stable or decreasing dose of steroids.
- For subjects with functional tumors that require treatment with SSAs for symptom control: a. Any subject receiving treatment with short acting octreotide, which cannot be interrupted for 24 hours before the administration of RYZ101. b. Any subject receiving treatment with octreotide LAR or lanreotide, which cannot be interrupted for at least 4 weeks before the administration of RYZ101.(Note: Long-acting SSAs can be transitioned to short-acting SSAs for these 4 weeks. Long-acting SSAs can be re-started as early as 4 hours after the end of a RYZ101 infusion.)
- Subject requires other treatment that in the opinion of the investigator would be more appropriate than the therapy offered in the study
- Unable or unwilling to comply with the requirements of the study protocol
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- Brazil
- United States
- Korea, Republic of
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; Brazil; United States; Korea, Republic of. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.