SKL35501 With SKL35502 Imaging in Adults With NTSR1 Positive Advanced Solid Tumors

NCT07812805 | Recruiting Phase 1 FDA Drug

• 1 other identifier: SKL35501C001
• Study Type: interventional
• Target: 100
• Locations: 2 countries
• Sites: 5

Brief 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.

Conditions

Selected Advanced Solid Tumors; Colorectal Cancer (CRC); Pancreatic Ductal Adenocarcinoma (PDAC); Biliary Tract Cancer (BTC); Gastric Cancer (GC); Esophageal Cancer (EC); Head and Neck Squamous Cell Cancer (HNSCC)

Outcome Measures

Primary Outcomes (16)

• Number of Participants With Treatment-Emergent Adverse Events Following SKL35502 Administration

  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.

  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.

• Absorbed Radiation Dose to Prespecified Normal Organs Following SKL35502 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.

  From SKL35502 administration through 7 days after administration.

• Absorbed Radiation Dose to Evaluable Tumor Lesions Following SKL35502 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.

  From SKL35502 administration through 7 days after administration.

• Whole-Body Radiation Dose Following SKL35502 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.

  From SKL35502 administration through 7 days after administration.

• Number of Participants With Dose-Limiting Toxicities During Cycle 1 Following the First Dose of SKL35501

  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.

  From the first administration of SKL35501 through the end of Cycle 1, a period of 6 weeks.

• Lower SKL35501 Administered Activity Selected for the Biologically Active Dose Range for Part B

  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.

  At completion of Part A dose escalation and backfill, after all Part A participants have completed at least one 6-week treatment cycle.

• Upper SKL35501 Administered Activity Selected for the Biologically Active Dose Range for Part B

  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.

  At completion of Part A dose escalation and backfill, after all Part A participants have completed at least one 6-week treatment cycle.

• Tumor-to-Background Ratio of SKL35502 Uptake in RECIST Version 1.1 Measurable Tumor Lesions

  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.

  From SKL35502 administration through 144 hours after administration.

• Number of Participants With at Least One SKL35502-Positive RECIST Version 1.1 Measurable Tumor Lesion

  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.

  From SKL35502 administration through 144 hours after administration.

• SKL35502 Imaging Time Point Selected for Tumor Eligibility Assessment

  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.

  At completion of the Part A SKL35502 imaging review following collection of imaging data through 144 hours after administration.

• Percentage of Participants With Complete Response, Partial Response, or Stable Disease Lasting at Least 4 Months Following SKL35501 Treatment

  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.

  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 Following SKL35501 Treatment

  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.

  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 Following SKL35501 Treatment

  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.

  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.

• Progression-Free Survival Following SKL35501 Treatment

  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.

  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.

• Time to Disease Progression Following SKL35501 Treatment

  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.

  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.

• Overall Survival Following SKL35501 Treatment

  Overall survival is defined as the time from the first administration of SKL35501 to death from any cause.

  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.

Secondary Outcomes (27)

• Number of Participants With Grade 3 or Higher 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.

• Number of Participants With Serious 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.

• Number of Participants With Adverse Events of Special Interest 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.

• Number of Participants With Clinically Significant 12-Lead Electrocardiogram Abnormalities Following SKL35502 Administration

  From baseline until initiation of SKL35501, 15 days after the last administration of SKL35502, or initiation of a new antitumor therapy, whichever occurs first.

• Number of Participants With Clinically Significant Vital-Sign Abnormalities Following SKL35502 Administration

  From baseline until initiation of SKL35501, 15 days after the last administration of SKL35502, or initiation of a new antitumor therapy, whichever occurs first.

Study Arms (2)

SKL35501 Low Dose

EXPERIMENTAL

Description: For dose optimization, one cohort with 2 groups (Low Dose SKL35501 group and High Dose SKL35501 group) will be initiated in part B of the study

Drug: SKL35501; Diagnostic Test: SKL35502

SKL35501 High Dose

EXPERIMENTAL

Description: For dose optimization, one cohort with 2 groups (Low Dose SKL35501 group and High Dose SKL35501 group) will be initiated in part B of the study

Drug: SKL35501; Diagnostic Test: SKL35502

Interventions

SKL35501 DRUG

Therapeutic agent that consists of an NTSR1-targeting small molecule linked to alpha emitter 225Ac to induce killing of NTSR1-expressing tumor cells

SKL35501 High Dose; SKL35501 Low Dose

SKL35502 DIAGNOSTIC_TEST

Imaging agent that consists of an NTSR1-targeting small molecule linked to 111In to detect NTSR1-expressing tumors via SPECT imaging

SKL35501 High Dose; SKL35501 Low Dose

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants are eligible to be included in the study only if all the following criteria apply:
• Signed ICF.
• Participants should be ≥ 18 years (in the US) or ≥19 years (in South Korea) of age at the time of signing the ICF.
• Histologically and/or cytologically confirmed diagnosis of selected advanced or metastatic solid tumors (relapsed/refractory disease).
• 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.
• 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:
• Residual neurological symptoms ≤ Grade 1
• 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
• Follow-up MRI or CT scan shows no progression of treated lesions and no new lesions.
• Measurable disease on imaging, as assessed by RECIST v1.1 and/or RANO-BM for brain metastases (Eisenhauer et al, 2009).
• ECOG performance status ≤ 2.
• Minimum life expectancy ≥ 12 weeks at enrollment as determined by investigator
• Willing to follow the contraception requirements as outlined:
• For females:
• WOCBP:

You may not qualify if:

• Patients are excluded from the study if any of the following criteria apply:
• Medical Conditions:
• Patients with evidence of hydronephrosis.
• 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).
• History of ascites or pleural effusion, unless successfully treated, asymptomatic, and not requiring treatment for \> 2 months prior to C1D1.
• History of and/or current cardiovascular events or conditions:
• History of myocardial infarction, unstable or severe angina, or arterial thrombotic event (such as CVA or TIA) within (≤) 12 months prior to C1D1
• Current NYHA stage II-IV congestive heart failure
• Unstable arrhythmia, or history or presence of a clinically significant (in the Investigator's opinion) ECG abnormality
• Screening QT (QTc) interval (average of triplicate measurements; corrected for heart rate using Fridericia's formula) \> 470 msec
• Uncontrolled hypertension, defined as SBP \> 150 mm Hg and/or DBP \> 100 mm Hg at screening, despite optimal antihypertensive therapy.
• Positive tests at screening for the following:
• 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.
• 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.

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (5)

United Theranostics

Glen Burnie, Maryland, 21061, United States

RECRUITING

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

NOT YET RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

NOT YET RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

NOT YET RECRUITING

The Catholic University of Korea, Seoul St. Mary's Hospital

Seoul, 06591, South Korea

NOT YET RECRUITING

MeSH Terms

Conditions

Colorectal Neoplasms; Biliary Tract Neoplasms; Stomach Neoplasms; Esophageal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Biliary Tract Diseases; Stomach Diseases; Head and Neck Neoplasms; Esophageal Diseases

Central Study Contacts

Ashley Villa

CONTACT

240-448-6111; avilla@sklsi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: In Part A, the first 3 patients in each cohort will be administered doses sequentially. Up to 4 dose levels of SKL35501 will be tested After dose levels 3 and 4, respectively, have been determined as safe, additional patients to a total of 6 patients will be recruited ("backfilling") to obtain further safety, tolerability, and preliminary activity data, and to select the most appropriate BADR for Part B of the study. Part B: Dose Optimization and Expansion Phase will have one cohort for dose optimization cohort (CRC patients) with 2 groups (Low Dose SKL35501 group and High Dose SKL35501 group). Treatment allocation to SKL35501 \[Low Dose\] or SKL35501 \[High Dose\] will occur in a randomized manner.

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: September 10, 2026
• Study Start: August 19, 2026
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: September 10, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

KR (3); US (2)