None listed
Conditions
Brief summary
This study aims to assess the safety and tolerability of two new drugs in patients with extensive stage small cell lung cancer (ES SCLC). The first drug (68Ga-SSO120/68Ga-Satoreotide Trizoxetan) is used as a tumour imaging agent for patients who have tumours with specific receptors, while the second drug (177Lu-SSO110) targets and damages cancer cells with these specific receptors. Who is it for? You may be eligible for this study if you are an adult aged 18 years or older, you have been diagnosed with extensive stage small cell lung cancer and if you are going to be receiving ICI maintenance therapy. All potential participants will be reviewed by the study investigators to ensure that they meet additional health criteria before enrolment. Study details All participants who choose to enrol in this study will undergo two screening scans using the new 68Ga-SSO120 imaging drug. The first scan will be to confirm eligibility to receive the 177Lu-SSO110 drug. If eligible, the first treatment dose with 177Lu-SSO110 will be scheduled at least 18 days after the 68Ga-SSO120 scan. The second scan with 68Ga-SSO120 will be taken at the end of treatment visit, which will be 6 weeks following the last dose of 177Lu-SSO110. For each scan, the 68Ga-SSO120 drug will be administered via an intravenous infusion 1 hour (40-90 minutes) before the PET/CT scan. The scans are anticipated to take 1-2 hours in total to complete. Participants who are confirmed to have somatostatin receptor 2 tumour cells based on the first screening scan will then be offered the opportunity to undergo treatment with the 177Lu-SSO110 drug. Participants who choose to enrol in the 177Lu-SSO110 arm of this study will have 177Lu-SSO110 administered via an intravenous infusion within 7 weeks after their last induction ICI therapy. Up to 3 additional 177Lu-SSO110 administration cycles will be given 6 to 9 weeks after the previous 177Lu-SSO110 administration. For participants with clinical benefit at the end of the 4 cycles the Investigator may request that the patient is provided with up to three additional treatments, which will be approved at the Sponsor’s discretion It is hoped this research will demonstrate that each of the study drugs, 68Ga-SSO120 and 177Lu-SSO110 are safe and well tolerated by patients with extensive stage small cell lung cancer. If the results of this initial study are positive, a larger trial involving a greater number of patients with extensive stage small cell lung cancer may be undertaken to further determine the potential benefits of the new drugs.
Interventions
This study involves the use of two investigational compounds in patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) receiving maintenance phase maintenance treatment with immune
checkpoint inhibition therapy (standard of care treatment for ES-SLSC).
The first is an investigational imaging product 68Ga-SSO120 (68Ga-Satoreotide Trizoxetan) which will be used for two screening scans that will be taken pre- and post- treatment dosing with 177Lu-SSO110. The first scan using 68Ga-SSO120
This study involves the use of two investigational compounds in patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) receiving maintenance phase maintenance treatment with immune checkpoint inhibition therapy (standard of care treatment for ES-SLSC). The first is an investigational imaging product 68Ga-SSO120 (68Ga-Satoreotide Trizoxetan) which will be used for two screening scans that will be taken pre- and post- treatment dosing with 177Lu-SSO110. The first scan using 68Ga-SSO120 will be at least 18 days prior to the planned first 177Lu-SSO110 dose. The second 68Ga-SSO120 scan will be performed at the end of treatment visit, which will be in the 6th week post the last dose of 177Lu-SSO110. All study participants (approx. 70) will undergo the screening with 68Ga-SSO120 as per the study eligibility screening criteria. 68Ga-Satoreotide Trizoxetan is an imaging agent for patients with somatostatin receptor 2 (SSR2) positive tumours. 68Ga-SSO120 will be administered intravenously 40-90 minutes before the PET/CT scan which will last approximately 15-30 minutes. To ensure adherence to the intervention a schedule of clinic and hospital visits will be given to the patients which encompasses their standard of care as well as their clinical trial treatment plan. To monitor patient adherence to the intervention, all patient visits (missed or attended) will be tracked in the site’s electronic medical record (EMR). All participants will receive up to 2 single doses of 68Ga-SSO120 (1 at screening and the other at the end of treatment visit), with 68Ga radioactivity of 150 MBq injected intravenously. The administered radiation dose will be 150 +/- 50 MBq, and the peptide mass dose up to 50 µg (prepared from a vial containing 50 µg of SSO120) infused by slow intravenous push and flushed with 10 mL of normal saline (0.9% sodium chloride solution), as appropriate. The second is an interventional radiopharmaceutical product 177Lu-SSO110 (177Lu-satoreotide tetraxetan) which is anticipated to be administered to approximately 30 of the 70 participants screened with 68Ga-SSO120. Four cycles of 177Lu-SSO110 therapy are planned per protocol each as a single intravenous infusion, with the first administered within 7 weeks of the last induction cycle of immune checkpoint inhibition therapy. The initial administered radiation dose of 177Lu-SSO110 will be 3.7 GBq with a potential dose escalation up to 5.2 GBq or de-escalation to 2.3 GBq. Dose escalation and de-escalation is for the purpose of establishing a Recommended Phase 2 Dose (RP2D). In this study the dose will be determined by the Safety Review Committee (SRC) who will be closely monitoring all patients for the incidence of dose limiting toxicities (DLTs) to determine the maximum tolerated dose of 177Lu-SSO110. Prior to participant dosing the SRC will review the incidence of any DLTs and will follow the protocol dose escalation guide (following a Bayesian Optimal Interval/BOIN) design) to provide the most appropriate dosing decision. Subsequent 177Lu-SSO110 administrations will be given 6 to 9 weeks after the preceding 177Lu-SSO110 administration. In the case of resolving toxicity, an extension of up to 12 weeks after the preceding 177Lu-SSO110 administration may be granted with subsequent 177Lu-SSO110 administration(s) also delayed accordingly. For participants with clinical benefit at the end of the 4 cycles the Investigator may request that the patient is provided with up to three additional treatments provided they meet all the criteria in in Section 9.6.5. of the protocol. 177Lu-SSO110 will be administered by intravenous infusion over up to 30 minutes using the hospital’s standard practice for peptide receptor radionuclide therapy - the preferred method for administration is the gravity method. Infusion rate can be modified (up or down) per the Investigator’s judgement and may be temporarily halted or further slowed down if the participant does not tolerate the infusion. The overall infusion duration should not exceed 60 minutes. Concomitant renal protection via amino acid infusion will be administered starting 30 minutes prior to 177Lu-SSO110 infusion and continuing for 4 hours as per the joint International Atomic Energy Agency (IAEA), European Association of Nuclear Medicine (EANM), and Society of Nuclear Medicine and Molecular Imaging (SNMMI) practical guidance on PRRT in NETs (Section 9.1.5 of the protocol). The duration and method of administration will be recorded in the case report form (CRF). All administration of treatment on the study will be conducted in a hospital setting and therefore adherence to their intervention schedule will be monitored in the clinic’s EMR.
Sponsors
Ariceum Therapeutics Australia Pty Ltd
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Aged at least 18 years (inclusive at the time of informed consent). 2. Must be able and willing to provide written informed consent prior to start of any study procedures and assessments and must be willing to comply with all study procedures. 3. Confirmation of SCLC by histology or cytology. Confirmation of extensive stage SCLC by imaging. 4. Adequate organ and marrow function within 7 days prior to the first dose of 177LuSSO110 as defined below: a. absolute neutrophil count >1,000/µL; b. platelets of >=100,000/µL; c. total bilirubin >=1.5 × upper limit of normal (ULN) or >=3.0 × ULN for participants with hereditary benign hyperbilirubinemia; d. AST (aspartate aminotransferase or serum glutamic oxaloacetic transaminase, SGOT) and ALT (alanine aminotransferase or serum glutamic pyruvic transaminase, SGPT) <=3 × ULN (or <=5 × ULN if liver metastases are present); e. serum creatinine <=1.5 × ULN; f. estimated glomerular filtration rate >=45 mL/min/1.73 m2 ; g. serum albumin >=30 g/L. 5. Life expectancy of >18 weeks at confirmation of eligibility, in the opinion of the Investigator. 6. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic gonadotropin test within 72 hours before the first dose of study drug and must not be breastfeeding. WOCBP are defined as those who are not surgically sterile or post-menopausal. Female participants will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. Female participants <50 years old who meet the criteria for post-menopausal status without previous surgical sterilization should be considered for further investigation with luteinising hormone and follicle stimulating hormone levels to confirm serological post-menopausal status. 7. WOCBP must agree to use a highly effective method of contraception during the study and for 90 days after the last dose of study drug. 8. Male participants who are able to father a child must agree to avoid impregnating a partner and to adhere to a highly effective method of contraception during the study and for 90 days after the last dose of study drug. All male participants must agree to not donate sperm during the study and for 90 days after the last dose of study drug. 9. Positive 68Ga-SSO120 scan at screening is mandatory (positive being at least one lesion concordant with a known lesion based on CT or FDGPET/CT with uptake visually assessed as greater than the liver on 68Ga-SSO120 scan). In case there are no visible lesions on CT (complete response) or a 68Ga-SSO120 scan cannot be performed due to technical reasons, a positive test for SST2 from archival tissue or cytology (e.g., Fine Needle Aspiration (FNA)) (positive being a H-score >50) is required. 10. To receive the first dose of 177Lu-SSO110, participants must have completed induction therapy with cisplatin/carboplatin, etoposide and ICI, and be eligible for maintenance therapy with an ICI. 11. Participants with brain metastases are eligible to participate if: a. they are clinically and radiologically stable disease (no evidence of progression by imaging; same imaging modality [magnetic resonance imaging or CT scan]) must be used for each assessment) for at least 28 days prior to the first dose of study drug; b. any neurologic symptoms returned to baseline; c. no longer on steroids. Note: Participants with a history of leptomeningeal disease may not participate even if stable clinically.
Exclusion criteria
8.2. Exclusion Criteria A participant who meets any of the following exclusion criteria must be excluded from the study: 1. Any previous radioligand therapy (e.g., peptide receptor radionuclide therapy). 2. Any concurrent malignancy. Patients with a malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this study at the Investigator’s discretion. 3. Any condition that precludes the adequate performance of PET and/or CT scan. 4. History of clinically significant allergic reactions attributed to compounds of similar chemical composition to 68Ga, 177Lu, SSO110, SSO120, ICI, somatostatin analogue peptides or other agents used in the study. 5. Any Grade >3 immune-related adverse event (irAE) during prior or current therapy with any immunotherapy agent(s). Previous irAEs thought not to increase participant’s risk of an investigational medicinal product-related AE, may be approved at the Investigator’s discretion, if it is determined as unlikely to put the participant at an increased risk of treatment-related toxicity and/or impact the integrity of study outcome (e.g., hypothyroidism on stable thyroxine replacement, adrenal insufficiency on stable hormone replacement therapy, diabetes on stable insulin therapy). 6. Use of immunosuppressive medication >10 mg prednisolone per day or equivalent within 14 days prior to the first dose of 177Lu-SSO110. Note: Use of immunosuppressive medications as prophylaxis in participants with contrast allergies are acceptable. In addition, temporary uses of corticosteroids considered nonclinically relevant may be approved at the Investigator’s discretion. 7. Any unresolved AEs Grade >1 from prior anticancer therapy except for alopecia. Participants with residual AEs Grade >1 considered unlikely to put the participant at an increased risk of treatment-related toxicity and/or impact the integrity of study outcome may be permitted on a case-by-case basis at the Investigator’s discretion (e.g., thyroid disorders or cortisol insufficiency on stable hormone replacement therapy). 8. Any uncontrolled intercurrent illness or clinically significant uncontrolled condition(s); active bacterial, fungal, or viral infections requiring systemic therapy. 9. Live vaccine administration <=21 days prior to the first dose of study drug. 10. Active or previous autoimmune diseases, with the following exemptions: a. Hashimoto’s thyroiditis on stable thyroid replacement therapy; b. Type 1 diabetes mellitus on stable insulin therapy; c. Other autoimmune disorders not considered to put participant at a higher risk of irAE may be approved at the Investigator’s discretion. 11. History of primary immunodeficiency, bone marrow (BM) transplantation, or solid organ transplantation. 12. History of inflammatory bowel disease, interstitial lung disease (pneumonitis), myocarditis, Stevens-Johnson syndrome, or toxic epidermal necrolysis. 13. History of known alcohol or substance abuse and/or a known psychiatric illness/social situation that would limit compliance with study requirements. 14. Has had or is scheduled to have major surgery <28 days prior to the first dose of study drug. 15. Known active human immunodeficiency virus or known active hepatitis B or C virus. 16. Known history within 4 months prior to first dose of study treatment or current symptomatic heart failure as per New York Heart Association classes III-IV, unstable angina, myocardial infarction, serious/uncontrolled/unstable cardiac arrhythmia, cerebral vascular accident, coronary/peripheral artery bypass graft surgery, transient ischemic attack, or pulmonary embolism. 17. Known history of severe asthma and/or chronic obstructive airways disease requiring systemic steroid therapy within 6 months prior to first dose of study treatment. Baseline oxygen saturation reading at room air must be >90% by pulse oximetry. 18. Known history of severe eczema and other skin/pruritic conditions requiring systemic steroid therapy within 6 months prior to first dose of study treatment. 19. Any extensive radiotherapy <=3 months before first 177Lu-SSO110 administration, defined as external beam radiation (e.g., stereotactic ablative radiotherapy) to >25% of the BM or brachytherapy. 20. A known superscan indicating extensive bony metastatic disease. 21. Received anticancer therapy (other than ICIs), including chemotherapy (except for ESSCLC induction chemotherapy), immunotherapy, biologic, herbal therapy, or any investigational therapy or investigational device, within 18 days (or 5 half-lives for biologic/non-cytotoxic agents, whichever is shorter), prior to the first dose of the study drug. 22. High risk of bleeding due to uncontrolled coagulopathies or unstable vascular malformations.
Outcome results
None listed