Study of RYZ101 in Combination With SoC in Subjects With SSTR+ ES-SCLC

Phase 1b Single Arm, Open-label Trial of RYZ101 in Combination With Carboplatin + Etoposide + Atezolizumab in Subjects With Somatostatin Receptor Expressing (SSTR+) Extensive Stage Small Cell Lung Cancer (ES-SCLC)

This study aims to determine the safety, preliminary antitumor activity, and pharmacokinetics (PK) of RYZ101 in combination with standard of care (SoC) therapy consisting of carboplatin + etoposide + atezolizumab in untreated subjects with somatostatin receptor expressing (SSTR+) ES-SCLC.

Study Overview

• Status: Active, not recruiting
• Conditions: SCLC,Extensive Stage
• Intervention / Treatment: Drug: Etoposide; Drug: Carboplatin; Drug: Atezolizumab; Drug: RYZ101 Dose Level 1; Drug: RYZ101 Dose Level 2; Drug: RYZ101 Dose Level 3; Drug: RYZ101 Dose Level -1

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Puerto Rico
  • Puerto Rico
    • San Juan, Puerto Rico, Puerto Rico, 00935
      • Research Facility
• United States
  • California
    • Los Angeles, California, United States, 90024
      • Research Facility
    • San Francisco, California, United States, 94158
      • Research Facility
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Research Facility
    • Miami, Florida, United States, 33136
      • Research Facility
    • Orlando, Florida, United States, 32806
      • Research Facility
  • Iowa
    • Iowa City, Iowa, United States, 52242
      • Research Facility
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Reserach Facility
  • Michigan
    • Grand Rapids, Michigan, United States, 49503
      • Research Facility
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Research Facility
  • Missouri
    • St Louis, Missouri, United States, 63130
      • Research Facility
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Facility
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Research Facility

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

INCLUSION CRITERIA

• Age of at least 18 years at the time of signing the informed consent.
• Cytologically or histologically confirmed ES-SCLC (American Joint Committee on Cancer [AJCC] 8th edition) and is untreated or received ≤1 cycle of platinum-etoposide and PD-L1 inhibitor therapy. It is acceptable to omit the first dose of PD-L1 inhibitor therapy due to logistical reasons if receiving SoC during or prior to the start of the screening period.

• Subject is a candidate for therapy with SoC which includes:

  • Carboplatin for a maximum of 4 cycles
  • Etoposide for a maximum of 4 cycles
  • Atezolizumab
• At least 1SSTR-PET imaging-positive measurable site of disease (according to RECIST v1.1) and ≥50% of RECIST v1.1 measurable metastatic lesions must be SSTR-imaging positive.
• Adequate hematologic, renal and hepatic function

EXCLUSION CRITERIA

• Prior exposure to immune-mediated therapy,
• Known active or suspected autoimmune disease or any condition requiring systemic treatment with immunosuppressive medications within 14 days prior to first dose of study drug
• History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis. Note: History of radiation pneumonitis is permitted.
• Severe infection within 4 weeks and/or treatment with therapeutic oral or i.v. antibiotics within 2 weeks prior to initiation of study treatment.
• Prior allogeneic stem cell or solid organ transplantation.
• Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.
• Radiotherapy to the chest prior to systemic therapy or planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed >2 weeks prior to first dose of study drug.
• Significant cardiovascular disease and/or resistant hypertension
• Subjects with previously treated central nervous system (CNS) metastases who have not recovered from acute side effects of radiotherapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RYZ101 + SoC	Drug: Etoposide; Etoposide; Drug: Carboplatin; Carboplatin; Drug: Atezolizumab; Atezolizumab; Drug: RYZ101 Dose Level 1; Dose Level 1; Drug: RYZ101 Dose Level 2; Dose Level 2; Drug: RYZ101 Dose Level 3; Dose Level 3; Drug: RYZ101 Dose Level -1; Dose Level -1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
RP2D	RP2D as determined by incidence rate of DLTs	42 days of study treatment
Safety and tolerability of RYZ101 in combination with SoC	Safety and tolerability of RYZ101 in combination with SoC as measured by incidence and severity of AEs including SAEs, laboratory changes and other safety findings	Up to 50 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Durable ORR	Durable ORR defined as the proportion of subjects with measurable disease at baseline who achieve confirmed CR or PR according to RECIST v1.1 lasting at least 4 months	Up to 50 months
ORR	ORR as assessed by the Investigator according to RECIST v1.1	Up to 50 months
DOR	Only for subjects with a RECIST v.1.1 response, assessed by the Investigator according to RECIST v1.1	Up to 50 months
OS	OS as defined from the time of first dose of RYZ101 or first dose of SoC therapy to the date of death due to any cause	Up to 50 months
BOR	BOR as assessed by the Investigator according to RECIST v1.1	Up to 50 months
Disease Control Rate	Disease control rate (PR + CR + SD) as assessed by the Investigator according to RECIST v1.1	Up to 50 months
PFS	PFS as defined from date of first dose of RYZ101 or first dose of SoC therapy to the date of progression as assessed by the Investigator according to RECIST v1.1	Up to 50 months
PK parameter: Maximum observed concentration (Cmax) of RYZ101 in combination with SoC		Up to 8 days
PK parameter: Time to maximum observed concentration (Tmax) of RYZ101 in combination with SoC		Up to 8 days
PK parameter: Area under the concentration-time curve (AUC) of RYZ101 in combination with SoC		Up to 8 days
PK parameter: Volume of distribution (V) of RYZ101 in combination with SoC		Up to 8 days
PK parameter: Terminal half life (T1/2) of RYZ101 in combination with SoC		Up to 8 days
PK parameter: Clearance of RYZ101 in combination with SoC		Up to 8 days

Collaborators and Investigators

• Sponsor: RayzeBio, Inc.
• Investigators: Study Director: Petrus De Jong, MD, RayzeBio, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2022
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: October 24, 2022
• First Posted (Actual): October 27, 2022

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: carboplatin; atezolizumab; ES-SCLC; etoposide; SCLC; radiopharmaceutical; targeted radiotherapy; actinium; alpha-emitter; SSTR+ ES-SCLC; RYZ101; 225Ac; 225Ac-DOTATATE
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Small Cell Lung Carcinoma; Organic Chemicals; Hydrocarbons; Hydrocarbons, Cyclic; Carbohydrates; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Glucosides; Glycosides; Coordination Complexes; Etoposide; Carboplatin; atezolizumab
• Other Study ID Numbers: RYZ101-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No