This is a Phase 0/1, First-in-Human (FIH), study to evaluate safety, tolerability, biodistribution, radiation dosimetry and preliminary anti-tumour activities of 177Lu-RAD204 in participants with selected solid tumours, to identify the MTDs/ recommended doses of 177Lu-RAD204 for future exploration.
The study will consist of a Pre-screening Period (if applicable for PD-L1 testing), a Screening Period of up to 4 weeks, followed by a Phase 0 (Imaging) Period for imaging and dosimetry to 177Lu-RAD204im and a Phase I (Treatment) Period for 177Lu-RAD204tr dose escalation.
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.
Adult participants ≥ 18 years of age.
Participants with a documented history of histopathologically confirmed relapsed/refractory locally advanced, inoperable or metastatic NSCLC, SCLC, TNBC, cutaneous melanoma, HNSCC, endometrial cancer or any cancer that is known to be MMR deficient or MSI high with documented disease progression during or after their most recent line of anticancer therapy. Participants must be refractory to or have refused standard of care therapy (including PD-1/PD-L1 inhibitors) or have refused or have no standard of care therapy available that is likely to provide clinical benefit.
If the participant tumour's PD-L1 expression status is unknown, PD-L1 positivity may be determined in a pre-screening step whereby the participant may be approached to provide written informed consent to have their tumour tissue undergo IHC testing as determined by a validated test (tumour tissue may be obtained from archived samples or from a freshly obtained biopsy).
History of prior organ transplant.
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.
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.
Residual toxicity ≥ Grade 2 from prior anti-cancer therapy (except alopecia).
Single group
177Lu-RAD204
Drug177Lu-RAD204 administered at Imaging (im) and Treatment (tr) doses
Time Activity Curves (TACs)
Percent of the injected activity vs time for selected organs and tumors
Radiation dosimetry of Lu177-RAD204im
Absorbed radiation doses of 177Lu-RAD204im in critical organs (e.g., kidneys, bone marrow)
Pharmacokinetics of 177Lu-RAD204im
Half-life of 177Lu-RAD204im in blood
Biokinetics of 177Lu-RAD204im
Time-integrated activity coefficients of 177Lu-RAD204im in organs and tumor lesions
Safety and tolerability of a single dose of 177Lu-RAD204im
The properties, incidence, nature and severity of AEs and SAEs per Common Terminology Criteria for Adverse Events (CTCAE) v5.0
Recommended dose(s) of 177Lu-RAD204im for future exploration
Incidence of dose-limiting toxicities (DLTs) in the first 2 weeks following 177Lu-RAD204im injection
Preliminary antitumor activity of 177Lu-RAD204tr
Objective response rates (ORR) as assessed by RECIST v1.1
Radiation dosimetry of 177Lu-RAD204tr
Absorbed radiation doses of 177Lu-RAD204tr in critical organs (e.g., kidneys, bone marrow)
Level of agreement between 177Lu-RAD204im and standard of care imaging
Standard of care imaging may include but is not limited to 18F-FDG-PET, CT-scan and/or 99mTc-MDP-bone
Effect of 177Lu-RAD204im and 177Lu-RAD204tr on tumor markers
Circulating tumor DNA
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