SCLC,Extensive Stage
Conditions
Keywords
actinium, alpha-emitter, SSTR+ ES-SCLC, SCLC, ES-SCLC, RYZ101, 225Ac, 225Ac-DOTATATE, targeted radiotherapy, atezolizumab, carboplatin, etoposide, radiopharmaceutical
Brief summary
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.
Interventions
DRUGRYZ101 Dose Level 1
Dose Level 1
DRUGRYZ101 Dose Level 2
Dose Level 2
DRUGRYZ101 Dose Level 3
Dose Level 3
DRUGRYZ101 Dose Level -1
Dose Level -1
DRUGAtezolizumab
Atezolizumab
DRUGCarboplatin
Carboplatin
DRUGEtoposide
Etoposide
Sponsors
RayzeBio, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| RP2D | 42 days of study treatment | RP2D as determined by incidence rate of DLTs |
| Safety and tolerability of RYZ101 in combination with SoC | Up to 50 months | 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 |
Countries
Puerto Rico, United States
Contacts
STUDY_DIRECTORPetrus De Jong, MD
RayzeBio, Inc.
Outcome results
None listed