Clinical Trials in the USA / NCT07812805
Recruiting
Phase 1
SKL35501 With SKL35502 Imaging in Adults With NTSR1 Positive Advanced Solid Tumors
NCT07812805 · tracked via the Priya Life Science USA tracker
Condition(s) studied
Selected Advanced Solid TumorsColorectal Cancer (CRC)Pancreatic Ductal Adenocarcinoma (PDAC)Biliary Tract Cancer (BTC)Gastric Cancer (GC)Esophageal Cancer (EC)Head and Neck Squamous Cell Cancer (HNSCC)
Investigational drug(s) / intervention(s)
SKL35501SKL35502
SKL35501: Therapeutic agent that consists of an NTSR1-targeting small molecule linked to alpha emitter 225Ac to induce killing of NTSR1-expressing tumor cells
SKL35502: Imaging agent that consists of an NTSR1-targeting small molecule linked to 111In to detect NTSR1-expressing tumors via SPECT imaging
Study summary
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 participants with colorectal cancer, and will expand evaluation in selected tumor types. The study will also examine relationships among SKL35502 imaging, NTSR1 expression, SKL35501 tumor uptake, and treatment outcomes.
Eligibility
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 carcinoma of the skin, or in situ cervical cancer, in situ breast cancer, in situ prostate cancer (patients must have shown no evidence of active disease for 2 years prior to enrollment).
3. History of ascites or pleural effusion, unless successfully treated, asymptomatic, and not requiring treatment for \> 2 months prior to C1D1.
4. History of and/or current cardiovascular events or conditions:
1. History of myocardial infarction, unstable or severe angina, or arterial thrombotic event (such as CVA or TIA) within (≤) 12 months prior to C1D1
2. Current NYHA stage II-IV congestive heart failure
3. Unstable arrhythmia, or history or presence of a clinically significant (in the Investigator's opinion) ECG abnormality
4. Screening QT (QTc) interval (average of triplicate measurements; corrected for heart rate using Fridericia's formula) \> 470 msec
5. Uncontrolled hypertension, defined as SBP \> 150 mm Hg and/or DBP \> 100 mm Hg at screening, despite optimal antihypertensive therapy.
5. Positive tests at screening for the following:
1. HIV: HIV patients on established ART for at least 4 weeks and have a viral load less than 400 copies/mL and CD4+ T-cell counts ≥350 μL may be eligible.
2. HBsAg: Patients with positive HBV test and HBV DNA \< 500 copies being treated with antivirals may participate.
i. HBcAb: Patients with a positive HBcAb test followed by a negative HBV DNA test at screening may be enrolled.
ii. HCV antibody test: Patients with a positive HCV antibody test followed by a negative HCV RNA test at screening may be enrolled.
6. Active thrombophlebitis, thromboembolism, hypercoagulability states, bleeding:
1. Patients with a history of DVT may participate if successfully treated, completely resolved, and no treatment has been given for \> 2 months.
2. Patients who suffered a thromboembolism \> 6 months prior and who are stable on anticoagulation may participate.
7. Uncontrolled diabetes.
8. Chronic severe liver disease or liver cirrhosis.
9. Any active or symptomatic persistent infection (bacterial, viral, or fungal) requiring systemic therapy within (≤) 14 days prior to C1D1.
10. Any psychiatric illness or social situation that would limit compliance with study requirements.
11. Any other significant co-morbidity, disease, metabolic dysfunction, physical examination, or clinical laboratory finding that contraindicates the use of an investigational drug, or may represent an unacceptable risk from treatment complications, or may affect adherence to the study procedures or the interpretation of the results.
Ineligible prior and ongoing treatment requirements:
12. Treatment with previous cancer therapies (including investigational cancer treatment) ≤ 28 days or 5 half-lives prior to C1D1, or radiation therapy within (≤) 4 weeks prior to start of SKL35502 (palliative radiation or stereotactic radiosurgery within (≤) 7 days prior to start of SKL35502). Patients must have recovered from all acute radiotherapy-related toxicities.
13. Prior radiopharmaceutical or radioligand therapy.
14. Patients who are receiving treatment with medications known to prolong the QT/QTc interval.
15. Live, attenuated vaccine within (≤) 28 days prior to C1D1, or anticipation of need for such a vaccine during the course of the study. COVID-19 vaccination is acceptable.
16. Any other therapy that is prohibited during the study. Refer to Section 6.9.1.
Other Exclusion Criteria:
17. Known hypersensitivity to SKL35502 or SKL35501 or any component(s) of SKL35502 or SKL35501.
18. Contraindications to or inability to perform the imaging procedures required in this study.
19. History of drug-induced anaphylactic or other severe hypersensitivity reactions.
20. History of any of the following: drug-induced SCAR; including but not limited to SJS/TEN, or DRESS syndrome), or dose-limiting immune-mediated reactions.
21. Current pregnancy and/or breast-feeding.
Primary outcome measure(s)
- Number of Participants With Treatment-Emergent Adverse Events Following SKL35502 Administration — From the first administration of SKL35502 until initiation of SKL35501, 15 days after the last administration of SKL35502, or initiation of a new antitumor therapy, whichever occurs first.
The number of participants with at least one treatment-emergent adverse event following administration of SKL35502 will be reported. A treatment-emergent adverse event is an adverse event that begins or worsens after the first administration of SKL35502. Adverse-event severity will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 6.0. Each participant will be counted once for this outcome regardless of the number of events experienced. - Absorbed Radiation Dose to Prespecified Normal Organs Following SKL35502 Administration — From SKL35502 administration through 7 days after administration.
Absorbed radiation dose will be estimated for each prespecified normal organ following SKL35502 administration using serial imaging, organ time-activity data, and protocol-defined dosimetry methods. Organ-specific absorbed-dose values will be reported separately using the same protocol-defined absorbed-dose unit. - Absorbed Radiation Dose to Evaluable Tumor Lesions Following SKL35502 Administration — From SKL35502 administration through 7 days after administration.
Absorbed radiation dose will be estimated for each evaluable tumor lesion following SKL35502 administration using serial imaging, lesion time-activity data, and protocol-defined dosimetry methods. Lesion-specific absorbed-dose values will be reported separately using the same protocol-defined absorbed-dose unit. - Whole-Body Radiation Dose Following SKL35502 Administration — From SKL35502 administration through 7 days after administration.
The whole-body radiation dose following SKL35502 administration will be estimated using serial imaging and protocol-defined dosimetry methods. One whole-body radiation-dose value will be reported for each evaluable participant using the protocol-defined unit. - Number of Participants With Dose-Limiting Toxicities During Cycle 1 Following the First Dose of SKL35501 — From the first administration of SKL35501 through the end of Cycle 1, a period of 6 weeks.
The number of participants who experience at least one SKL35501-related dose-limiting toxicity during the protocol-defined dose-limiting toxicity assessment period will be reported. Dose-limiting toxicities are protocol-defined hematologic or non-hematologic adverse events occurring during the first treatment cycle. Each participant will be counted once regardless of the number of dose-limiting toxicities experienced. - Lower SKL35501 Administered Activity Selected for the Biologically Active Dose Range for Part B — At completion of Part A dose escalation and backfill, after all Part A participants have completed at least one 6-week treatment cycle.
The lower SKL35501 administered activity selected for the biologically active dose range will be determined by the Safety Review Committee based on integrated review of dose-limiting toxicities, safety and tolerability beyond the dose-limiting toxicity assessment period, pharmacokinetics, pharmacodynamics, imaging, dosimetry, and preliminary antitumor activity. One lower administered-activity value will be reported in megabecquerels. - Upper SKL35501 Administered Activity Selected for the Biologically Active Dose Range for Part B — At completion of Part A dose escalation and backfill, after all Part A participants have completed at least one 6-week treatment cycle.
The upper SKL35501 administered activity selected for the biologically active dose range will be determined by the Safety Review Committee based on integrated review of dose-limiting toxicities, safety and tolerability beyond the dose-limiting toxicity assessment period, pharmacokinetics, pharmacodynamics, imaging, dosimetry, and preliminary antitumor activity. One upper administered-activity value will be reported in megabecquerels. - Tumor-to-Background Ratio of SKL35502 Uptake in RECIST Version 1.1 Measurable Tumor Lesions — From SKL35502 administration through 144 hours after administration.
Tumor-to-background ratio will be calculated as SKL35502 uptake in an anatomically matched RECIST Version 1.1 measurable tumor lesion divided by uptake in the background reference region defined in the Imaging Charter or Imaging Manual. Tumor-to-background ratio values will be summarized separately at each protocol-specified imaging time point. - Number of Participants With at Least One SKL35502-Positive RECIST Version 1.1 Measurable Tumor Lesion — From SKL35502 administration through 144 hours after administration.
The number of participants with at least one anatomically matched RECIST Version 1.1 measurable tumor lesion demonstrating focal SKL35502 uptake above the Imaging Charter-defined background region will be reported. Positivity will be assessed by a qualified nuclear medicine physician or radiologist using the protocol-defined visual and quantitative imaging criteria. - SKL35502 Imaging Time Point Selected for Tumor Eligibility Assessment — At completion of the Part A SKL35502 imaging review following collection of imaging data through 144 hours after administration.
The imaging time point selected for tumor eligibility assessment will be determined based on integrated review of tumor visualization, tumor-to-background ratio, normal-tissue uptake, image quality, biodistribution, and operational feasibility. One selected imaging time point will be reported as the number of hours after SKL35502 administration. - Percentage of Participants With Complete Response, Partial Response, or Stable Disease Lasting at Least 4 Months Following SKL35501 Treatment — Tumor assessments will be performed every 8 weeks during the first 6 months and every 12 weeks thereafter, up to 12 months after the last participant's first SKL35501 dose.
The percentage of efficacy-evaluable participants whose best overall response is complete response or partial response, or whose stable disease lasts for at least 4 months, will be reported. Tumor response will be assessed by the Investigator according to RECIST Version 1.1 and, where applicable, RANO-BM for brain metastases. - Objective Response Rate Following SKL35501 Treatment — Tumor assessments will be performed every 8 weeks during the first 6 months and every 12 weeks thereafter, up to 12 months after the last participant's first SKL35501 dose.
Objective response rate is the percentage of efficacy-evaluable participants whose best overall response is complete response or partial response, as assessed by the Investigator according to RECIST Version 1.1 and, where applicable, RANO-BM for brain metastases. - Clinical Benefit Rate Following SKL35501 Treatment — Tumor assessments will be performed every 8 weeks during the first 6 months and every 12 weeks thereafter, up to 12 months after the last participant's first SKL35501 dose.
Clinical benefit rate is the percentage of efficacy-evaluable participants whose best overall response is complete response, partial response, or stable disease, as assessed by the Investigator according to RECIST Version 1.1 and, where applicable, RANO-BM for brain metastases. - Progression-Free Survival Following SKL35501 Treatment — From the first SKL35501 dose until documented disease progression, death, or completion of protocol-defined efficacy follow-up, up to 12 months after the last participant's first SKL35501 dose.
Progression-free survival is defined as the time from the first administration of SKL35501 to the first documented disease progression, as determined by the Investigator according to RECIST Version 1.1 and, where applicable, RANO-BM for brain metastases, or death from any cause, whichever occurs first. - Time to Disease Progression Following SKL35501 Treatment — From the first SKL35501 dose until documented disease progression or completion of protocol-defined efficacy follow-up, up to 12 months after the last participant's first SKL35501 dose.
Time to disease progression is defined as the time from the first administration of SKL35501 to the first documented disease progression, as determined by the Investigator according to RECIST Version 1.1 and, where applicable, RANO-BM for brain metastases. - Overall Survival Following SKL35501 Treatment — From the first SKL35501 dose until death, loss to follow-up, withdrawal of consent, or completion of protocol-defined survival follow-up, up to 12 months after the last participant's first SKL35501 dose.
Overall survival is defined as the time from the first administration of SKL35501 to death from any cause.
Trial sites (5)
| Facility | City | Region | Status |
|---|---|---|---|
| United Theranostics | Glen Burnie | Maryland | Recruiting |
| UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania | Not Yet Recruiting |
| Seoul National University Hospital | Seoul | South Korea | Not Yet Recruiting |
| Asan Medical Center | Seoul | South Korea | Not Yet Recruiting |
| The Catholic University of Korea, Seoul St. Mary's Hospital | Seoul | South Korea | Not Yet Recruiting |
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Official registry record
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
View NCT07812805 on ClinicalTrials.gov ↗ ← All trials in the USA