💬In plain words
What the trial is, and whether it could suit you
This Phase 1, open-label study will evaluate two investigational radiopharmaceuticals in adults with selected advanced or metastatic solid tumors. SKL35502 is an imaging agent used with SPECT scans to identify tumors with neurotensin receptor 1 (NTSR1), a protein found on some cancer cells, and to assess where the agent travels in the body and the radiation dose delivered to tissues. Participants with sufficient SKL35502 tumor uptake may receive SKL35501, a treatment designed to deliver targeted alpha radiation to NTSR1-expressing tumor cells.
Part A will evaluate the safety and imaging performance of SKL35502 and the safety, tolerability, pharmacokinetics, biodistribution, dosimetry, and biologically active dose range of SKL35501, as well as preliminary antitumor activity. Part B will further evaluate selected SKL35501 dose levels, including randomized low- and high-dose groups in part
Sign in to get the eligibility rules as simple questions to take to your doctor.
📋 Eligibility rules (as published)
Inclusion Criteria
Participants are eligible to be included in the study only if all the following criteria apply:
1. Signed ICF.
2. Participants should be ≥ 18 years (in the US) or ≥19 years (in South Korea) of age at the time of signing the ICF.
3. Histologically and/or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors (relapsed/refractory disease).
4. Selected advanced solid tumors (PDAC, CRC, BTC, HNSCC, EC, and GC) with sufficient target (NTSR1) expression confirmed by SKL35502 imaging as defined in Inclusion Criterion 5, that have progressed following at least one prior line of therapy or for which no other standard therapy with proven clinical benefit is currently available or recommended based on the Investigator's individual risk-benefit assessment. Patients with MSI-H/dMMR CRC must have previously received and progressed on, been intolerant to, or been deemed ineligible for an FDA-approved immune checkpoint inhibitor, unless such therapy is contraindicated.
5. Sufficient target (NTSR1) expression on SKL35502 imaging, defined as uptake above background in at least 1 RECIST v1.1 measurable lesion, with background activity defined in accordance with the Imaging Charter. For study eligibility, NTSR1 positivity will be determined locally at the site by the Investigator based on review by a qualified site nuclear medicine physician/radiologist, as applicable. SKL35502 images and required lesion documentation will also be submitted for central review for dosimetry, biodistribution, lesion alignment, image quality control, and consistency of image analyses across sites. Central review will not replace the site determination of eligibility except in equivocal cases requiring adjudication.
6. Patients with secondary metastasis to the CNS are eligible if they have had all brain metastases resected or have received radiation therapy ending at least 4 weeks prior to C1D1 and they meet all of the following criteria:
1. Residual neurological symptoms ≤ Grade 1
2. No glucocorticoids requirement or patients may be receiving low doses of glucocorticoids (not exceeding a dose equivalent to prednisone 10 mg daily), provided the dose has been stable for at least 2 weeks prior to C1D1
3. Follow-up MRI or CT scan shows no progression of treated lesions and no new lesions.
7. Measurable disease on imaging, as assessed by RECIST v1.1 and/or RANO-BM for brain metastases (Eisenhauer et al, 2009).
8. ECOG performance status ≤ 2.
9. Minimum life expectancy ≥ 12 weeks at enrollment as determined by investigator
10. Willing to follow the contraception requirements as outlined:
1. For females:
WOCBP:
* Must have a negative serum pregnancy test performed within (≤) 14 days prior to dosing with SKL35502 (where demanded by local regulations; test may be required within 24 hrs. prior to dosing).
* Compliant with at least 2 highly effective contraceptive methods (e.g., oral contraceptives, IUD, condom with spermicide, etc.) throughout the study and for at least 8 months (i.e., corresponding to 5 half-lives + 6 months) following the last dose of SKL35501.
* Female patients must not be pregnant or lactating at study screening and during the course of the study and must not become pregnant for at least 8 months (i.e., corresponding to 5 half-lives + 6 months) following the last dose of SKL35501.
* Abstinence is not considered an adequate contraceptive method on its own.
* Women of non-childbearing potential:
* Must be surgically sterile (e.g., tubal occlusion, hysterectomy, bilateral salpingectomy) or postmenopausal (defined as no menstrual cycle for at least 12 consecutive months).
2. For males:
* Must be surgically sterile, or compliant with a contraceptive method (effective barrier contraception, such as a condom with spermicide) during the study and then for at least 5 months (i.e., corresponding to 5 half-lives + 3 months) after the last dose of SKL35501.
* Must agree not to donate sperm during the study until 90 days after the last dose of SKL35501.
* Male patients with female partner(s) of childbearing potential:
* Female partner must use a highly effective method of contraception (e.g., oral contraceptives, IUD, diaphragm, etc.) during the study and 5 months (i.e., corresponding to 5 half-lives + 3 months) following the male patient's last dose of SKL35501.
* Male patients with female partner(s) of non-childbearing potential (i.e., postmenopausal or surgically sterile for at least 6 months prior to Screening):
* No additional contraception method is required.
11. Adequate hematologic and end-organ function, defined based on the following laboratory results obtained within (≤) 14 days prior to C1D1:
1. ANC ≥ 1.5 × 109/L (1500/μL), without G-CSF support. G-CSF may be administered until (\>) 14 days prior to C1D1.
2. Platelet counts ≥ 100 × 109/L (100,000/μL) without receiving any thrombopoietin receptor agonists, other therapies for thrombocytopenia or platelet transfusion for ≥ 14 days prior to C1D1.
3. Hemoglobin ≥ 90 g/L (9 g/dL). Patients may be transfused or receive erythropoietic treatment to meet this criterion until (\>) 14 days prior to C1D1.
4. AST and ALT ≤ 3 × ULN (≤ 5 × ULN for patients with documented liver metastases).
5. Total bilirubin ≤ 1.5 × ULN (≤ 3 × ULN for patients with Gilbert's syndrome).
6. eGFR ≥ 60 mL/min (multiply the estimate of GFR by individual's BSA (calculated using an appropriate formula) and divide by 1.73 m2).
7. Albumin \> 28 g/L
Exclusion Criteria
Patients are excluded from the study if any of the following criteria apply:
Medical Conditions:
1. Patients with evidence of hydronephrosis.
2. History of solid tumor malignancy other than the diseases under study, diagnosed within (≤) the last 3 years of study enrollment, excluding adequately treated basal cell carcinoma of the skin, squamous cell carc