Trial Title:
177Lu-anti-PD-L1 SdAb in Metastatic Non-small Cell Lung Cancer
NCT ID:
NCT06305962
Condition:
PDL1 Gene Mutation
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Conditions: Keywords:
PDL1 Positive
Non Small Cell Lung Cancer
Study type:
Interventional
Study phase:
Early Phase 1
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
177Lu-RAD204
Description:
177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses
Arm group label:
177Lu-RAD204
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.
Criteria for eligibility:
Criteria:
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 (β-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.
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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Nepean Hospital
Address:
City:
Kingswood
Zip:
2747
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Veronica Wong, MD
Phone:
+61024734 2156
Email:
Veronica.Wong@health.nsw.gov.au
Facility:
Name:
Wollongong Hospital
Address:
City:
Wollongong
Zip:
2500
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Daniel Brungs, MD
Email:
daniel.brungs@health.nsw.gov.au
Facility:
Name:
Cancer Research SA (CRSA)
Address:
City:
Adelaide
Zip:
5000
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Vineet Kwatra, MD
Phone:
+610883592565
Email:
vkwatra@crsa.au
Facility:
Name:
Hollywood Private Hospital
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Joe Cardaci, MD
Phone:
0893862844
Email:
jcardaci@dni.com.au
Start date:
June 3, 2024
Completion date:
October 2025
Lead sponsor:
Agency:
Radiopharm Theranostics, Ltd
Agency class:
Industry
Source:
Radiopharm Theranostics, Ltd
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06305962