Safety, Tolerability, PK/PD & Preliminary Efficacy of SKL27969 in Advanced Solid Tumors Patients

NCT05388435 | Terminated Phase 1 DMC FDA Drug

• 1 other identifier: SKL27969C001
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 4

Brief Summary

Primary Objective of Part 1 (Dose Escalation Phase): Evaluate the safety and tolerability of SKL27969, and determine the maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of SKL27969 Primary Objective of Part 2 (Dose Expansion Phase): Evaluate the preliminary anti-tumor activity of SKL27969

Conditions

Advanced Solid Tumor

Keywords

Advanced Malignant Solid Tumors; Glioblastoma; Non-Small Cell Lung Cancer; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (6)

• Part 1 (Dose Escalation Phase) - Numbers of participants with adverse events, dose interruptions and modifications

  Any incidence of AEs, dose interruptions and dose modifications from signing of Informed Consent Form (ICF) until discontinuation and/or protocol required Survival Follow-up is completed.

  1 year

• Part 1 (Dose Escalation Phase) - Number of participants with dose limiting toxicities

  The Dose Limiting Toxicities (DLTs) are based on drug related adverse events and defined as any of the following events: hematological / non-hematological toxicity of Grade 3 or higher.

  1 year

• Part 1 (Dose Escalation Phase) - Number of participants with abnormal assessments

  Post baselines changes in laboratory assessments, vital signs, electrocardiograms (ECGs) and physical examinations related to SKL27969.

  1 year

• Part 2 (Dose Expansion Phase) - Number of participants with partial response data

  ORR is defined as the proportion of participants who have a partial response (PR) or better according to the RECIST version 1.1 or RANO.

  30 months

• Part 2 (Dose Expansion Phase) - Number of participants with progression-free survival

  Each participant will be assessed for progression-free survival (PFS) starting from first day of treatment until disease progression according to RECIST version 1.1 or RANO.

  30 months

• Part 2 (Dose Expansion Phase) - Number of participants with overall survival

  Each participant will be assessed for overall survival (OS) starting from first day of treatment until death.

  30 months

Secondary Outcomes (18)

• Part 1 (Dose Escalation Phase) - Number of participants with partial response data

  1 year

• Part 2 (Dose Expansion Phase) - Number of participants with adverse events, dose interruptions and modifications

  30 months

• Part 2 (Dose Expansion Phase) - Pharmacokinetics of SKL27969

  30 months

• Part 2 (Dose Expansion Phase) - Pharmacokinetics of SKL27969

  30 months

• Part 2 (Dose Expansion Phase) - Pharmacokinetics of SKL27969

  30 months

Study Arms (2)

Part 1: Dose Escalation Phase

EXPERIMENTAL

Part 1 is a dose escalation phase to evaluate the safety, tolerability, and define the MTD and RP2D. Part 1 is a 3+3 design.

Drug: SKL27969

Part 2: Dose Expansion Phase

EXPERIMENTAL

Part 2 includes tumor-specific expansion cohorts utilizing the MTD/RP2D doses (determined from Part 1) to further explore safety and anti-tumor activity of SKL27969, in addition to the PK and PD from the patients with the selected tumor types.

Drug: SKL27969

Interventions

SKL27969 DRUG

SKL27969 will be orally administered once daily on an intermittent dosing schedule (3 days on and 4 days off).

Part 1: Dose Escalation Phase; Part 2: Dose Expansion Phase

Eligibility Criteria

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

You may qualify if:

• Willing to provide written, voluntary informed consent prior to any study-specific procedures;
• Male and female patients at least 18 years of age at the time of informed consent;
• Histologically or cytologically confirmed diagnosis of non-resectable or metastatic solid malignancy that is refractory (radiographic documentation of progression) or intolerant of established therapies known to provide clinical benefit for the malignancy in the opinion of the Investigator;
• Evidence of radiological progressive disease and minimum life expectancy of at least months, in the judgement of the Investigator;
• Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 or Response Assessment in Neuro-Oncology (RANO), with the last imaging performed within 28 days before Cycle 1 Day 1, and documented disease progression during or after their most recent line of anticancer therapy;
• \. Prior treatment required for the following diagnoses that are histologically and molecularly confirmed:
• Recurrent high-grade glioma (HGG) (e.g., anaplastic astrocytoma (high grade), recurrent ependymoma BRAFV600E or GBM) must have biopsy proven evidence according to 2021 World Health Organization (WHO) classification (Grade 3 or 4) and received:
• \- Radiotherapy with at least 2 cycles of temozolomide chemotherapy
• NSCLC of any histologic sub-type with local mutational analysis; must have received platinum-based therapy, immune checkpoint inhibitor and targeted tyrosine kinase inhibitor, if mutation present for approved agent in accordance with product labels; or
• TNBC must have biopsy proven evidence according to the American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines and received
• Checkpoint inhibitors for patients who are PD-L1 positive;
• PARP inhibitors for patients with germline BRCA mutations; or
• Targeted antibody-drug conjugates, such as Sacituzumab govitecan.
• Must have recovered to Grade 1 from the effects of any prior investigational systemic therapies; with the exception of alopecia and Grade 2 peripheral neuropathy;
• Recurrent HGG must be neurologically stable for 7 or more days and takes no more than 2 mg or 4 mg of dexamethasone or equivalent steroid per day;

You may not qualify if:

• Patient has had 1 or more of the following cardiac function criteria:
• Clinically meaningful unstable angina;
• Myocardial infarction within 6 months prior to starting the study treatment;
• New York Heart Association Class II or greater congestive heart failure;
• QT interval corrected using Fridericia's formula \>470 msec obtained as the mean from 3 consecutive resting ECGs;
• Clinically significant abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block, third degree heart block);
• Ongoing congestive heart failure or cardiac dysrhythmias of National Cancer Institute (NCI) Common Terminology Criteria for AEs (CTCAE) greater than or equal to Grade 2 or uncontrolled atrial fibrillation;
• Congenital long QT syndrome;
• Cerebrovascular accident within 6 months prior to starting the study treatment; or
• Clinically significant arterial hypertension despite medical treatment.
• Female patient is pregnant, breast-feeding, intending to donate ova, or planning to become pregnant before, during or within at least 90 days after the final study drug administration;
• Male patient intends to father or donate sperm during the study or for at least 90 days after the final study drug administration;
• History of major gastrointestinal surgery, inflammation, or condition that can impair absorption of study drug;
• Evidence of infections (including chronic hepatitis type B or C and human immunodeficiency virus (HIV) infection, if status known);
• Active infection requiring intravenous (IV) antibiotics;

Sponsors & Collaborators

• SK Life Science, Inc.: lead

Study Sites (4)

City of Hope

Duarte, California, 91010, United States

Location

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Carolina BioOncology Institute

Huntersville, North Carolina, 28078, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Glioblastoma; Carcinoma, Non-Small-Cell Lung; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Vijaykumar Vashi, PhD

  SK Life Science, Inc.

  STUDY CHAIR

Study Design

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

Model Details: Part 1, Phase 1 Dose Escalation and Part 2, Phase 2 Dose Expansion

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: May 24, 2022
• Study Start: September 12, 2022
• Primary Completion: March 1, 2024
• Study Completion: March 1, 2024
• Last Updated: May 4, 2025

Record last verified: 2025-04

Locations

US (4)