Trial Review

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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT06305962




Registration number
NCT06305962
Ethics application status
Date submitted
22/02/2024
Date registered
12/03/2024
Date last updated
22/05/2024

Titles & IDs
Public title
177Lu-anti-PD-L1 sdAb in Metastatic Non-small Cell Lung Cancer
Scientific title
Phase 0/1 Study of the Safety and Tolerability of 177Lu-RAD204, a Lutetium-177 Radiolabelled Single Domain Antibody Against Programmed Cell Death-Ligand 1 in Patients With Metastatic Non-small Cell Lung Cancer
Secondary ID [1] 0 0
177Lu-RAD204.2023.0001
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
PDL1 Gene Mutation 0 0
Non Small Cell Lung Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma
Cancer 0 0 0 0
Lung - Non small cell
Cancer 0 0 0 0
Lung - Small cell

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - 177Lu-RAD204

Experimental: 177Lu-RAD204 - Single-arm, open-label study of 177Lu-RAD204 consisting of a Phase 0 Imaging Period (Im) and a Phase 1 Treatment Period (Tr).


Treatment: Drugs: 177Lu-RAD204
177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Time Activity Curves (TACs)
Timepoint [1] 0 0
72 hours
Primary outcome [2] 0 0
Radiation dosimetry of Lu177-RAD204im
Timepoint [2] 0 0
72 hours
Primary outcome [3] 0 0
Pharmacokinetics of 177Lu-RAD204im
Timepoint [3] 0 0
72 hours
Primary outcome [4] 0 0
Biokinetics of 177Lu-RAD204im
Timepoint [4] 0 0
72 hours
Primary outcome [5] 0 0
Safety and tolerability of 177Lu-RAD204tr
Timepoint [5] 0 0
6 weeks
Primary outcome [6] 0 0
Recommended dose(s) of 177Lu-RAD204tr for future exploration
Timepoint [6] 0 0
6 weeks
Secondary outcome [1] 0 0
Safety and tolerability of a single dose of 177Lu-RAD204im
Timepoint [1] 0 0
6 weeks
Secondary outcome [2] 0 0
Recommended dose(s) of 177Lu-RAD204im for future exploration
Timepoint [2] 0 0
2 weeks
Secondary outcome [3] 0 0
Preliminary antitumor activity of 177Lu-RAD204tr
Timepoint [3] 0 0
Up to 30 weeks
Secondary outcome [4] 0 0
Radiation dosimetry of 177Lu-RAD204tr
Timepoint [4] 0 0
72 hours

Eligibility
Key inclusion criteria
1. Willing and able to provide informed consent prior to start of any study procedures
and assessments and must be willing to comply with all study procedures.

2. Adult participants = 18 years of age.

3. Participants with a documented history of histopathological confirmed metastatic NSCLC
that is unresectable, progressive and for which standard treatment measures are no
longer effective.

4. Participants with a documented history of PD-L1 positive NSCLC. Any number of prior
treatment lines are allowed in this study, however at least one of the treatment
line(s) must include an anti-PD(L)-1 antibody. Participants with any documented PD-L1
positivity by immunohistochemistry (IHC) without prior treatment with anti-PD(L)-1
antibody may be allowed on a case-by-case basis in discussion with study Sponsor, if
it is determined not to put the participant at an increased risk of adverse drug
effects and/or interfere with the integrity of study outcome.

5. Eastern Cooperative Oncology Group (ECOG) performance status = 2.

6. Participants must have a life expectancy of >4 months in the opinion of the
Investigator.

7. Women of childbearing potential (WOCBP) must have a negative beta-human chorionic
gonadotropin (ß-hCG) test and must not be breastfeeding. WOCBP are defined as those
who are not surgically sterile or post-menopausal. Female subjects will be considered
post-menopausal if they have been amenorrheic for 12 months without an alternative
medical cause. Female subjects < 50 years old who meet the criteria for
post-menopausal status without previous surgical sterilization should be considered
for further investigation with luteinizing hormone (LH) and follicle stimulating
hormone (FSH) levels to confirm serological post-menopausal status.

8. WOCBP must agree to use a highly effective method of contraception during the study
and for 14 days after the last injection of 177Lu-RAD204im and/or 6 months after the
last dose of 177Lu-RAD204tr, whichever occurs later. Acceptable methods of
contraception are described the Protocol.

9. Male subjects 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 14 days after the last injection of 177Lu-RAD204im and/or 6 months after the
last dose of 177Lu-RAD204tr, whichever occurs later. All male subjects must agree to
not donate sperm during the study and for 14 days after the last injection of
177Lu-RAD204im and/or 4 months after the last dose of Lu-RAD204tr, whichever occurs
later. Acceptable methods of contraception are described in the Protocol.

10. Subjects with previously treated brain metastases are eligible to participate if: they
are clinically and radiologically stable (no evidence of progression by imaging; same
imaging modality [magnetic resonance imaging (MRI) or computed tomography (CT) scan]
must be used for each assessment) for at least 28 days prior to the first dose of
177Lu-RAD204; and any neurologic symptoms returned to baseline. Note: Subjects with a
history of leptomeningeal disease may not participate even if stable clinically.

11. For Phase I: Participants must have positive lesion(s) by 177Lu-RAD204im SPECT/CT as
described in Image Review Manual. Estimated total radiation dose to healthy organs
derived from phase 0 dosimetry must not exceed dose constraints according to the
American Association of Physicists in Medicine Quantitative Analysis of Normal Tissue
Effect in the Clinic (QUANTEC) and International Commission on Radiological Protection
(ICRP), in discussion with study Sponsor.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. History of prior organ transplant.

2. Any other known, active malignancy, except for treated cervical intraepithelial
neoplasia, or non-melanoma skin cancer. Patients with a history of malignancies of low
recurrence potential who have received curative-intent therapy may be approved on a
case-by-case basis in discussion with study Sponsor, if it is determined not to put
the patient at an increased risk of adverse drug effects and/or interfere with the
integrity of study outcome.

3. Have any medical condition that would, in the Investigator's judgment, prevent the
participant's full participation in the clinical study due to safety concerns or
compliance with clinical study procedures such as participants with severe
claustrophobia who are unresponsive to oral anxiolytics, participants with low back
pain who cannot lie comfortably on an imaging table, participants who are hyperactive
or hyperkinetic such that they cannot tolerate lying still for multiple time point
imaging procedures, etc.

4. Residual toxicity > Grade 1 from prior anti-cancer therapy (except alopecia).
Participants with > Grade 1 toxicity from prior anti-cancer therapy may be approved on
a case-by-case basis in discussion with study Sponsor, if it is determined not to put
the patient at an increased risk of adverse drug effects and/or interfere with the
integrity of study outcome.

5. History of uncontrolled allergic reactions and/or known or expected hypersensitivity
to protein therapeutics, 177Lu-RAD204 or any of its excipients.

6. Inadequate organ functions as reflected in laboratory parameters:

- Creatinine clearance (calculated using Cockcroft-Gault formula, or measured) < 60
mL/min or serum creatinine >1.5 x upper limit of normal (ULN)

- Platelet count of < 75 x 109/L

- Absolute neutrophil count (ANC) < 1.0 x 109/L

- Haemoglobin < 9 g/dL

- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3 x ULN, or
> 5 x ULN for patients with known liver metastases

- Total bilirubin > 1.5 x ULN, except for patients with documented Gilbert's
syndrome who are eligible if total bilirubin = 3 x ULN

- For participants not taking warfarin or other anticoagulants: international
normalized ratio (INR) =1.5 or prothrombin time (PT) =1.5 x ULN; and either
partial thromboplastin time or activated partial thromboplastin time (PTT or
aPTT) =1.5 x ULN. Participants taking warfarin must be on a stable dose that
results in a stable INR <3.5. Among participants receiving other anticoagulant
therapy, PT or aPTT must be within the intended therapeutic range of the
anticoagulant.

7. Patients requiring blood product transfusion within 4 weeks of first dose of
177Lu-RAD204tr are not eligible to participate.

8. Clinically significant cardiovascular disease including but not limited to:

- Unstable angina or acute myocardial infarction within 6 months prior to screening

- Clinically significant and/or uncontrolled heart disease such as congestive heart
failure requiring treatment (New York Heart Association (NYHA) grade = 2)

- Uncontrolled arterial hypertension or unstable clinically significant arrhythmia

- Known LVEF < 50%

- QTcF > 470 msec for females and QTcF > 450 msec for males on screening
electrocardiogram (ECG) or congenital long QT syndrome.

9. Participation in any other investigational trial at the time of informed consent
signature.

10. Pregnant or lactating women.

The following exclusion criteria apply to participants in Phase I:

11. Major surgery within 4 weeks prior to first dose of 177Lu-RAD204tr. Exceptions may be
approved on a case-by-case basis in discussion with study Sponsor, if it is determined
not to put the participant at an increased risk of adverse drug effects and/or
interfere with the integrity of study outcome.

12. Received anti-cancer therapy, including chemotherapy, immunotherapy, radiation
therapy, biologic, herbal therapy, or any investigational therapy or investigational
device, within 28 days (or 5 half-lives for biologic/noncytotoxic agents, whichever is
shorter), prior to the first dose of 177Lu-RAD204tr. Focal palliative radiotherapy
given within 28 days prior to the first dose of 177Lu-RAD204tr may be approved on a
case-by-case basis in discussion with the Sponsor, if it is determined not to put the
participant at an increased risk of adverse drug effects and/or interfere with the
integrity of study outcome. For participants who received radiotherapy more than 28
days prior to the first dose of 177Lu-RAD204tr, efforts should be made to calculate
the prior radiation absorbed dose to each critical organ such as the kidneys, liver,
lungs, and bone marrow. The absorbed dose limits for critical organs should not exceed
the cumulative absorbed dose from the prior radiopharmaceutical and/or external beam
radiation therapy (EBRT) treatment(s) and the planned course of treatment in this
study. Participants who would have cumulative absorbed dose to critical organs
exceeded will not be enrolled in the study.

13. Has had or is scheduled to have major surgery < 28 days prior to the first dose of
177Lu-RAD204tr. Elective surgical procedures not considered to put participants at
higher risk of AEs may be allowed on a case-by-case basis in discussion with the
Sponsor.

14. Positive status for human immunodeficiency virus (HIV).

15. Active or chronic hepatitis B or C. Chronic hepatitis B or hepatitis C with
undetectable viral loads on stable suppression therapy may be allowed on a
case-by-case basis in discussion with study Sponsor.

16. Any medical condition which, in the opinion of the Investigator, places the
participant at an unacceptably high risk for toxicities.

17. Any uncontrolled intercurrent illness or clinically significant uncontrolled
condition(s), including but not limited to active bacterial, fungal, or viral
infections requiring systemic therapy.

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 0
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/06/2024
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/10/2025
Actual
Sample size
Target
23
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,WA
Recruitment hospital [1] 0 0
Wollongong Hospital - Wollongong
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
Hollywood Private Hospital - Nedlands
Recruitment postcode(s) [1] 0 0
2500 - Wollongong
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Radiopharm Theranostics, Ltd
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
This is a first-in-human, open-label study consisting of a Screening Period, an Imaging
Period, and a Treatment Period in eligible non-small lung cancer patients who are positive
for the biomarker PDL-1. The Screening period lasts up to 4 weeks. The Phase 0 (Imaging
Period) is used to determine if patient's tumor(s) are still positive for the biomarker, as
well as radiation dosimetry with low dose 177Lu-RAD204im (for a period of up to 2 weeks
following the first injection of 177Lu-RAD204im), to assess the safety of the drug. Following
the 2 week safety assessment, the subject is eligible to enter Phase I (Treatment Period)
with gradual dose increases of 177Lu-RAD204tr. The Treatment Period lasts up to 3 cycles
every 6 weeks, with additional extension to a maximum study dose interval of 12 weeks to be
approved on a case-by-case basis in discussion with study Sponsor. During the Treatment
Period, subjects will be assessed for both safety and treatment response using conventional
images and clinical laboratory tests.
Trial website
https://clinicaltrials.gov/ct2/show/NCT06305962
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Kenneth O'Byrne, MD
Address 0 0
Country 0 0
Phone 0 0
+610449091958
Fax 0 0
Email 0 0
kenneth.obyrne@health.qld.gov.au
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT06305962