Clinical trial NCT06771219: SLV-154 Treatment of Metastatic Solid Tumors
Official title: A Phase 1 Dose-Escalation Study of SLV-154 in Subjects With Metastatic Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Squamous Cell Cancer of Head and Neck (SCCHN)
NSCLC
SCLC
Cervical Cancer Metastatic
Breast Cancer Metastatic
Endometrial Cancer
Ovarian Cancer
Urothelial Cancer
Sarcoma
Keywords: metastatic solid tumors
metastatic cancer
solid tumor
Lead sponsor: Solve Therapeutics
Sponsor class: INDUSTRY
First posted: 2025-01-13
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: In this study, a BOIN design with a target DLT rate for the MTD of 27% and an estimated maximum sample size of \~70 subjects will be used to guide the dose escalation and determine the RDR of SLV-154.
Primary purpose: TREATMENT

Brief summary: This is a Phase 1 dose-escalation study evaluating the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and efficacy of SLV-154 across a range of dose levels when administered to subjects with metastatic solid tumors.

Detailed description: A Bayesian optimal interval (BOIN) design with a target dose-limiting toxicity (DLT) rate for the maximum tolerated dose (MTD) of 27% and an estimated maximum sample size of \~70 subjects will be used to guide the dose escalation and determine the recommended dosing regimen (RDR) of SLV-154.

SLV-154 will be administered intravenously (IV) in repeated 3-week cycles. Treatment will continue until progressive disease or discontinuation.

Eligibility criteria: Inclusion Criteria:

1. Men or women (as appropriate for cancer type) of age ≥18 years.
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
3. Histologically or cytologically confirmed diagnosis of solid tumor as documented in medical records with the primary history comprising one of the following:

   1. SCCHN
   2. NSCLC
   3. SCLC
   4. Breast cancer
   5. Cervical cancer
   6. Endometrial cancer
   7. Ovarian cancer
   8. Urothelial cancer
   9. Sarcoma
4. Presence of metastatic disease that has progressed during or following previous treatment.
5. Presence of radiographically measurable disease.
6. Prior receipt of commercially available therapies that are indicated for the subject's cancer and have demonstrated survival benefit for that indication.
7. Availability of tumor tissue from a fresh tumor biopsy obtained by a core needle, excisional, or incisional biopsy; or punch biopsy (for cutaneous disease); or archival tumor sample from a previous biopsy.
8. Availability of computed tomography (CT) or magnetic resonance imaging (MRI) of chest, abdomen, and pelvis, and/or fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT (if appropriate for tumor type) (with PET from base of the skull to mid-thigh, if performed) within 35 days before study drug administration.
9. Completion of all previous therapy (including surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, or investigational therapy) for the treatment of cancer ≥1 week before the start of study drug administration.
10. Adequate hematological profile.
11. Adequate coagulation profile.
12. Adequate hepatic profile.
13. Adequate renal function.
14. Negative viral serology or adequate therapy for human immunodeficiency virus (HIV), hepatitis B (HBV), and hepatitis C (HCV) infection.
15. For female subjects of childbearing potential, a negative serum pregnancy test.
16. For female subjects of childbearing potential, willingness to use a protocol-recommended method of contraception from the start of the screening period until ≥6 months after the final dose of study therapy.
17. For male subjects who can father a child and are having intercourse with females of childbearing potential who are not using adequate contraception, willingness to use a protocol-recommended method of contraception from the start of study therapy until ≥6 months after the final dose of study therapy and to refrain from sperm donation from the start of study therapy until ≥12 months after administration of the final dose of study therapy.
18. Willingness and ability of the subject to comply with scheduled visits, the drug administration plan, protocol-specified laboratory tests, other study procedures (including required tumor biopsy/aspirations and/or radiographic studies), and study restrictions.
19. Evidence of a personally signed informed consent indicating that the subject is aware of the neoplastic nature of the disease and has been informed of the procedures to be followed, the experimental nature of the therapy, alternatives, potential risks and discomforts, potential benefits, and other pertinent aspects of study participation.

Exclusion Criteria:

1. Malignancy involving the central nervous system unless brain metastases have been previously treated with radiotherapy, have been stable for ≥4 weeks, and do not require corticosteroids.
2. Presence of another cancer with disease manifestations or therapy that could adversely affect subject safety or longevity, create the potential for drug-drug interactions, or compromise the interpretation of study results.
3. Uncontrolled ongoing systemic bacterial, fungal, or viral infection (including upper respiratory tract infection) at the time of start of study therapy.
4. Significant cardiovascular event or comorbidity.
5. Significant screening ECG abnormalities.
6. Pregnancy or breastfeeding.
7. Major surgery within 4 weeks before the start of study therapy.
8. Use of a strong inhibitor or inducer of CYP3A4 or CYP1A2.
9. Use of a drug known to prolong the QT interval within 7 days prior to the start of study drug administration.
10. Concurrent participation in another therapeutic or imaging clinical trial.
11. Other conditions likely to interfere with a subject's ability to participate in the study.

Primary outcomes:
measure: MTD and/or RDR
timeFrame: Through the duration of treatment, up to approximately 18 months
Secondary outcomes:
measure: SLV-154 administration
timeFrame: Through the duration of treatment, up to approximately 18 months
measure: Safety
timeFrame: Through the duration of treatment, up to approximately 18 months
measure: Evaluation of use of concomitant medications
timeFrame: Through the duration of treatment, up to approximately 18 months
measure: Pharmacokinetics
timeFrame: Varying timepoints through the duration of treatment, up to approximately 18 months
measure: Immunogenicity
timeFrame: Varying timepoints through the duration of treatment, up to approximately 18 months
measure: Objective Response Rate (ORR)
timeFrame: Through the duration of treatment, up to approximately 18 months
measure: Time to Response (TTR)
timeFrame: Up to approximately 36 months
measure: Duration of Response (DOR)
timeFrame: Up to approximately 36 months
measure: Progression-free survival (PFS)
timeFrame: Up to approximately 36 months
measure: Time to treatment failure (TTF)
timeFrame: Up to approximately 36 months
measure: Overall survival (OS)
timeFrame: Up to approximately 36 months
Other outcomes:
Locations:
city: St. Louis
country: United States
facility: Washington University
state: Missouri
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
References: