ANZCTR - Registration

Registration number

ACTRN12623000185662

Ethics application status

Approved

Date submitted

30/01/2023

Date registered

22/02/2023

Date last updated

4/08/2023

Date data sharing statement initially provided

22/02/2023

Type of registration

Prospectively registered

Titles & IDs

Public title

Satoreotide Theranostic Pilot study in Extensive Stage in Small Cell Lung Cancer (ES-SCLC)

Scientific title

A multicentre, open-label, Phase I study investigating the safety, tolerability, and efficacy of 177Lu-SSO110 with 68Ga-SSO120 companion imaging in participants with extensive stage small cell lung cancer (ES-SCLC) who are on maintenance treatment with atezolizumab

Secondary ID [1]

SSO110-01

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Extensive Stage Small Cell Lung Cancer

Condition category

Condition code

Cancer

Lung - Small cell

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

This study involves the use of two investigational compounds in patients with Extensive Stage Small Cell Lung Cancer (ES-SCLC) receiving maintenance phase atezolizumab 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 the 7 days after the first or second atezolizumab maintenance 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 (again within 7 days following an atezolizumab therapy). 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.

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

There is no comparator group for this study. Approximately 70 participants will undergo screening with 68Ga-SSO120. It is anticipated that approximately 30 of the 70 screened patients may respond positively to the 68Ga-SSO120 scan and therefore demonstrate SST2 expression. These patients will enter then be eligible to enter the treatment period and will be administered 177Lu-SSO110 therapy. Participants who demonstrate non-responsiveness to the 68Ga-SSO120 scan will be considered screen failures. Furthermore patients who do not undergo 68Ga-SSO120 will also be screen failures and therefore will not act as comparators.

One of the main objectives for this phase I study is to determine the Recommended Phase II Dose (RP2D) and therefore a comparator will not be required to be utilised.

Control group

Uncontrolled

Outcomes

Primary outcome [1]

Safety and tolerability of 177Lu-SSO110 as evaluated by:
• the incidence, properties, nature and severity of Drug-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
• abnormal laboratory parameters as assessed by safety blood tests
• vital signs (including body weight & height)
• ECG results
as reported and documented in the patient’s medical record and SAE reports.

Timepoint [1]

AEs & SAEs will be assessed continuously from the time of consent until the completion of the end of treatment visit (or end of study if earlier than end of treatment), defined as the date of the last visit of the last participant in the study or two years after the last patient was enrolled, whichever occurs first.

After the end of treatment visit, study drug related AEs will continue to be reviewed during long term follow up every 12 ± 4 weeks until withdrawal of consent, death, study completion, or study termination, whichever occurs earlier.

Laboratory tests and vital signs will be assessed at every study visit from the first screening visit with 68Ga-SSO120 until the until the end of treatment visit (6 + 1 weeks post final dose of 177Lu-SSO110), and at other times if deemed necessary by the Investigator.

12–lead ECGs will be performed at the Screening Visit, pre-dose at atezolizumab administration visits and at the end of treatment visit.

Primary outcome [2]

Safety and tolerability of 68Ga-SSO120 as evaluated by:
• the incidence, properties, nature and severity of Drug-related Adverse Events (AEs) and Serious Adverse Events (SAEs)
• abnormal laboratory parameters as assessed by safety blood tests
• vital signs (including body weight & height)
• ECG results
as reported and documented in the patient’s medical record and SAE reports.

Timepoint [2]

AEs & SAEs will be assessed continuously from the time of consent until the completion of the end of treatment visit (or end of study if earlier than end of treatment), defined as the date of the last visit of the last participant in the study or two years after the last patient was enrolled, whichever occurs first.

After the end of treatment visit, study drug related AEs will continue to be reviewed during long term follow up every 12 ± 4 weeks until withdrawal of consent, death, study completion, or study termination, whichever occurs earlier.

Laboratory tests and vital signs will be assessed at every study visit from the first screening visit with 68Ga-SSO120 until the until the end of treatment visit (6 + 1 weeks post final dose of 177Lu-SSO110), and at other times if deemed necessary by the Investigator.

12–lead ECGs will be performed at the Screening Visit, pre-dose at atezolizumab administration visits and at the end of treatment visit.

Primary outcome [3]

Incidence of dose limiting toxicities (DLTs) as evaluated by:
• blood samples and electrocardiogram (ECG) results
• incidence of AEs considered related to study drug(s) that occur during the observation period. E.g. Haematological AE (e.g. grade 4 neutropenia =7 consecutive days)

Timepoint [3]

The DLT observation period is from the first dose of 177Lu-SSO110 until end of treatment visit, whether it is due to completion of administration or discontinuation of study drugs due to toxicity or confirmed disease progression.

Secondary outcome [1]

Antitumour activity of 177Lu-SSO110 in participants on maintenance atezolizumab therapy as assessed by Overall Survival (OS)

Overall Survival (OS) as assessed by reports of:
- participant death and Progression Free Survival (PFS),
- Overall Response Rate (ORR),
- Duration of Response (DoR) and
- Disease Control Rate (DCR)
as assessed by the Investigator using RECIST criteria v1.1.

Timepoint [1]

Assessed continuously from first therapeutic intervention until either complete response, partial response, disease progression or death.

Secondary outcome [2]

Percent concordance between lesions visible on 68Ga-SSO120 scan versus lesions visible on native contrast enhanced computed tomography (ceCT) and/or fluorodeoxyglucose (FDG) PET/CT on a lesion level (by participant and overall)

Timepoint [2]

Assessed continuously from first therapeutic intervention until either complete response, partial response, disease progression or death.

Secondary outcome [3]

Exploratory – predictive factors for toxicity following treatment with 177Lu-SSO110 as assessed by investigations that may include but are not limited to blood samples for anti-drug antibodies (atezolizumab), tumour profiling (e.g. next-generation sequencing), activity kinetics of SSO110 assessed by dosimetry and lean body mass as calculated from CT scans.

Timepoint [3]

Anti-atezolizumab antibodies will be assessed on day 1 and at the end of treatment visit and End of Treatment Visit

Tumour profiling if conducted as standard practice at the study site

Activity kinetics assessed by dosimetry at each dosing visit of 177Lu-SSO110

Lean body mass will be assessed centrally, post-hoc from CT images obtained at screening and the end of treatment visits

Secondary outcome [4]

Exploratory – predictive factors for efficacy

Timepoint [4]

Anti-atezolizumab antibodies will be assessed on day 1 and at the end of treatment visit and End of Treatment Visit

Tumour profiling if conducted as standard practice at the study site
Activity kinetics assessed by dosimetry at each dosing visit of 177Lu-SSO110

Secondary outcome [5]

Exploratory – anti-tumour activity of 177Lu-SSO110 compared with historical controls of study derived endpoints of tumour activity (Overall Survival, Progression Free Survival, Overall Response Rate and Duration of Response), and historical controls available from trials of atezolizumab used with platinum based therapies and etoposide.

Timepoint [5]

Assessed at the end of study using study derived endpoints

Secondary outcome [6]

Exploratory – tumour response over time as assessed by comparison of study derived endpoints of tumour activity and historical controls available from trials of atezolizumab used with platinum based therapies and etoposide.

Also assessed using study related CT, MRI, SPECT and PET scans.

Timepoint [6]

Assessed during data analysis following the end of the study, defined as the date of the last visit of the last participant in the study or two years after the last patient was enrolled, whichever occurs first.

Eligibility

Key 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. Histologically or cytologically confirmed ES-SCLC.
4. Adequate organ and marrow function within 7 days of first dose of 177Lu-SSO110 as defined below:
a. absolute neutrophil count greater than or equal to 1,000/µL;
b. platelets of greater than or equal to 100,000/µL;
c. total bilirubin less than or equal to 1.5 × upper limit of normal (ULN) or less than or equal to 3.0 × ULN for participants with hereditary benign hyperbilirubinaemia;
d. AST (aspartate aminotransferase or serum glutamic oxaloacetic transaminase, SGOT) and ALT (alanine aminotransferase or serum glutamic pyruvic transaminase, SGPT) less than or equal to 3 × ULN (or less than or equal to 5 × ULN if liver metastases are present);
e. serum creatinine less than or equal to 1.5 × ULN;
f. estimated glomerular filtration rate greater than or equal to 45 mL/min/1.73 m2;
g. serum albumin greater than or equal to 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 amenorrhoeic 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. Either positive 68Ga-SSO120 scan at screening (positive being a lesion concordant with a known lesion based on CT or FDG-PET/CT with uptake visually assessed as greater than the liver on 68Ga-SSO120 scan) or at the Investigator’s discretion, in the case of no/insufficient visible lesions at screening, a positive test for SST2 from archival tissue or histology report (positive being a H-score >50).
10. To receive the first dose of 177Lu-SSO110, participants must have received at least 1 and no more than 2 doses of maintenance atezolizumab after induction therapy consisting of a platinum-based agent (e.g., cisplatin/carboplatin), etoposide and atezolizumab.
11. Participants with previously treated 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.

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key 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 and participants with a prior malignancy that have shown evidence of complete remission 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, atezolizumab, 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 non-clinically 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 less than or equal to 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 less than or equal to 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 atezolizumab), including 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.

Study design

Statistical methods / analysis

Recruitment

Recruitment status

Recruiting

Date of first participant enrolment

Anticipated

30/03/2023

Actual

30/06/2023

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

70

Accrual to date

3

Final

Recruitment in Australia

Recruitment state(s)

NSW,QLD,WA,VIC

Funding & Sponsors

Funding source category [1]

Commercial sector/Industry

Name [1]

Ariceum Therapeutics Australia Pty Ltd

Country [1]

Australia

Primary sponsor type

Commercial sector/Industry

Name

Ariceum Therapeutics Australia Pty Ltd

Country

Australia

Secondary sponsor category [1]

Commercial sector/Industry

Name [1]

GenesisCare Clinical CRO Pty Ltd

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Bellberry Human Research Ethics Committee

Ethics committee address [1]

123 Glen Osmond Road Eastwood Adelaide
South Australia 5063

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

14/12/2022

Approval date [1]

09/02/2023

Ethics approval number [1]

2022-12-1368

Summary

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 atezolizumab 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 7 days after their first or second atezolizumab maintenance therapy. Up to 3 additional 177Lu-SSO110 administration cycles will be given 6 to 9 weeks after the previous 177Lu-SSO110 administration (each within 7 days following an atezolizumab therapy). 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.

Trial website

Public notes

Contacts

Principal investigator

Name

Prof Joe Cardaci

Address

Diagnostic Nuclear Imaging, Hollywood Private Hospital, 101 Monash Avenue Nedlands 6009 WA

Country

Australia

Phone

+61412556901

Email

jcardaci@dni.com.au

Contact person for public queries

Name

Mr Ben Wyse

Address

GenesisCare Clinical CRO
Building 7, The Mill, 41-43 Bourke Road
Alexandria NSW 2015

Country

Australia

Phone

+61 491 819 717

Email

Ben.Wyse@genesiscare.com

Contact person for scientific queries

Name

Prof Joe Cardaci

Address

Diagnostic Nuclear Imaging, Hollywood Private Hospital, 101 Monash Avenue Nedlands 6009 WA

Country

Australia

Phone

+61 08 9366 1111

Email

jcardaci@dni.com.au

Trial Review

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