A single arm, open-label Phase 1b dose-escalation and expansion study of treatment of ES-SCLC with RYZ101 in combination with standard of care (SoC) carboplatin + etoposide + atezolizumab
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)
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Clinical Trial Information
Trial Contact: Simoni, Christine; Caldwell, Chloe M; Rodriguez Saavedra, Carlis M; Frankos, Marie
Trial Phone: 321.841.7293 ; (321)841.1107 ; 321.841.6764 ; 321.841.7303
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IRB No: Pro00065591
Protocol Abbrev: RYZ101-101
Principal Investigator: Justin Mathew Rineer, MD
Phase: Drug: Phase I
Age Group: Adult
ClinicalTrials.gov ID: NCT05595460
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Objective
To determine the RP2D of RYZ101 in combination with SoC carboplatin + etoposide + atezolizumab in subjects with untreated SSTR+ ES-SCLC
To assess the safety and tolerability of RYZ101 in combination with SoC in subjects with untreated SSTR+ ES-SCLC -
Key Eligibility
Inclusion Criteria
Subjects must meet all the following criteria for enrollment in the study:
1. Age of at least 18 years at the time of signing the informed consent.
2. Cytologically or histologically confirmed proven ES-SCLC (Stage IV [T any, N any, M
1a/b/c] or T 3-4 due to multiple lung nodules or tumor/nodal volume that is not amenable to a tolerable radiation plan) (NCCN v 1.2022, American Joint Committee on Cancer [AJCC] 8th edition) and is untreated or received ≤1 cycle of platinum-etoposide and PD-L1 inhibitor therapy (including SoC administered during screening, if applicable). It is acceptable to omit the first dose of PD-L1 inhibitor therapy due to logistical reasons if receiving SOC during the screening period.
3. If available, submit an archival tumor tissue sample that was obtained prior to administration of any systemic anti-ES-SCLC treatment, accompanied by the pathology report.
4. Subject is a candidate for therapy with SoC which includes:
a. Carboplatin for a maximum of 4 cycles
b. Etoposide for a maximum of 4 cycles
c. Atezolizumab
5. Eastern Cooperative Oncology Group (ECOG) PS 0-1.
6. Life expectancy of at least 12 weeks.
7. There must be at least 1 SSTR-positron emission tomography (PET) imaging-positive (using a regulatory agency-approved imaging method, e.g., Gallium-68 [68Ga], Copper-64 [64Cu]), not previously irradiated, measurable site of disease (according to RECIST v1.1) and ≥50% of RECIST v1.1 measurable metastatic lesions must be regulatory agency-approved SSTR imaging positive (SSTR imaging-positive is defined as uptake greater than the liver uptake observed on regulatory agency-approved SSTR PET imaging, i.e., Krenning score 3 or 4)
(Hope et al. 2019).
a. Computed tomography (CT)/magnetic resonance imaging (MRI) scans should be completed within 4 weeks prior to first dose of RYZ101 or first dose of SoC therapy, whichever is administered first, and regulatory agency approved SSTR PET imaging scans should be completed within 6 weeks prior to first dose of RYZ101.
b. For subjects who will receive the first cycle of SoC therapy during screening, the baseline CT/MRI is to be obtained before initiation of SoC therapy and the SSTR-PET should preferably be obtained before initiation of SoC therapy.
8. Sufficient renal function, as evidenced by creatinine clearance (CrCl) ≥60 mL/min (calculated using the Cockcroft-Gault formula) (Cockcroft and Gaul, 1976) (Appendix 5).
9. Subjects should have ionized calcium ≤1.5 mmol/L, calcium ≤12 mg/dL, or corrected calcium lower than the upper limit of normal (ULN).
10. Adequate hematologic function, defined by the following laboratory results:
a. Hemoglobin concentration ≥5.0 mmol/L (≥8.0 g/dL); absolute neutrophil count (ANC) ≥1000 cells/μL (≥1000 cells/mm3); platelets ≥70 × 109/L (70 × 103/mm3). Transfusion and/or use of hematopoietic factor therapies are not permitted within 14 days prior to date of screening laboratory tests unless clinically indicated following initiation of first cycle of SoC therapy.
11. Adequate hepatic function, defined by the following laboratory results:
a. Total bilirubin ≤1.5 × ULN (for patients with documented Gilbert syndrome, direct bilirubin must be ≤1.5 × ULN and enrollment requires approval by the medical monitor).
b. Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤2.5 × ULN (AST and ALT ≤5 × ULN in the presence of hepatic metastases).
12. For women of childbearing potential (WOCBP):
a. Negative serum pregnancy test within 48 hours prior to the first dose of study drug.
b. Agreement to use barrier contraception and a second form of highly effective contraception (Clinical Trials Facilitation Group [CTFG] 2014) while receiving study drug and for 6 months following their last dose of RYZ101/SoC. 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. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.
c. A woman is considered to be of childbearing potential if she is post-monarchal, has not reached a postmenopausal state (≥12 continuous months of amenorrhea [no menstrual bleeding of any kind, including menstrual period, irregular bleeding, spotting, etc.] 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 drug).
13. Sexually active male subjects must use a condom during intercourse while receiving study drug and for 3 months after the last dose of the study drug 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 (CTFG 2014) while receiving study drug and for 3 months following their last dose of RYZ101/SoC. 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.
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.
14. Able to read and/or understand the details of the study and provide written informed consent prior to any study-specific assessments and procedures commence. Note: for subjects who plan to receive SoC treatment during the screening period, written informed consent is not required before the start of SoC chemotherapy or the start of standard procedures to evaluate the subject’s appropriateness for SoC therapy.
