Safety and Efficacy of KLS-1 Monotherapy in Malignant Neoplasms

NCT06506643 | Recruiting Phase 1

• 1 other identifier: VV022-02
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the safety and preliminary efficacy of a new drug, KLS-1, in adults with different types of solid tumors and chronic lymphocytic leukemia (CLL). The main questions it aims to answer are:

• To define Dose Limiting Toxicities (DLT) and maximum tolerated dose (MTD) of KLS-1
• To select the recommended Phase II Dose (P2D) of KLS-1
• To determine the single dose and multiple dose PK profile following IV administration of KLS-1
• What is the safest and most effective dose of KLS-1?
• Does KLS-1 show anti-tumor activity in patients?
• To evaluate preliminary efficacy of KLS-1 in up to 4 cohorts of locally advanced or metastatic solid tumor (malignant melanoma, prostate cancer, pancreatic cancer), or CLL.
• To evaluate 12-months progression-free survival (PFS) and duration of response (DOR) follow-up after the last dose of KLS-1 Participants will:
• Receive KLS-1 through intravenous (IV) infusions in 21-day cycles.
• Be monitored for side effects and improvements in their malignancy. Investigators will compare different doses of KLS-1 in the initial phase to find the best dose for Phase II. Once the P2D is defined, it will be tested in a larger group to see its effects on locally advanced or metastatic solid tumor (malignant melanoma, prostate cancer, pancreatic cancer) and CLL.

Conditions

CLL; Solid Tumor, Adult

Keywords

malignant melanoma; prostate cancer; pancreatic cancer; CLL; chronic lymphocytic leukemia; Zn; Zinc; KLS-1; Malignant Neoplasms; Neoplasms; Metastatic Tumors; Zinc Aspartate

Outcome Measures

Primary Outcomes (5)

• Number of participants with Dose Limiting Toxicities (DLTs)

  Dose Limiting Toxicities (DLTs) at Dose Escalation Cohorts

  Cycle 1 Day 1, Cycle 1 Day 3, Cycle 1 Day 6, Cycle 1 Day 9, Cycle 1 Day 12, Cycle 1 Day 21, 30-Day Follow-Up (Each cycle is 28 days)

• Number of participants with Dose Limiting Toxicities (DLTs)

  Dose Limiting Toxicities (DLTs) at Dose Confirmation Cohorts

  Cycle 1 Day 1, Cycle 1 Day 3, Cycle 1 Day 6, Cycle 1 Day 9, Cycle 1 Day 12, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 6, Cycle 2 Day 12, Cycle 2 Day 21, 30-Day Follow-Up (Each cycle is 28 days)

• Number of participants with Treatment Emergent Adverse Events (AEs)

  Adverse Events (AEs) as characterized by type, frequency, severity as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, timing, seriousness and relationship to study therapy

  Cycle 1 Day 1, Cycle 1 Day 3, Cycle 1 Day 6, Cycle 1 Day 9, Cycle 1 Day 12, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 6, Cycle 2 Day 12, Cycle 2 Day 21, 30-Day Follow-Up (Each cycle is 28 days)

• Number of participants with Treatment Emergent Serious Adverse Events (SAEs)

  Serious Adverse Events (SAEs) as characterized by type, frequency, severity as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE), version 5.0, timing, seriousness and relationship to study therapy

  Cycle 1 Day 1, Cycle 1 Day 3, Cycle 1 Day 6, Cycle 1 Day 9, Cycle 1 Day 12, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 6, Cycle 2 Day 12, Cycle 2 Day 21, 30-Day Follow-Up (Each cycle is 28 days)

• Number of participants with Overall Response Rate (ORR)

  ORR evaluated upon using RECIST, version 1.1 and the based on International Workshop on Chronic Lymphocytic Leukemia (iwCLL) response criteria per Investigator assessment

  30-Day Follow-up, Q 3-Months Follow-up, 12-Months Follow -up

Secondary Outcomes (8)

• Cmax of KLS-1

  Cycle 1 Day 1,Cycle 1 Day 3, Cycle 1 Day 9, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 21 (Each cycle is 28 days)

• AUC0-t and AUC0-∞ of KLS-1

  Cycle 1 Day 1,Cycle 1 Day 3, Cycle 1 Day 9, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 21 (Each cycle is 28 days)

• T1/2 of KLS-1

  Cycle 1 Day 1,Cycle 1 Day 3, Cycle 1 Day 9, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 21 (Each cycle is 28 days)

• Tmax of KLS-1

  Cycle 1 Day 1,Cycle 1 Day 3, Cycle 1 Day 9, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 21 (Each cycle is 28 days)

• CL/F of KLS-1

  Cycle 1 Day 1,Cycle 1 Day 3, Cycle 1 Day 9, Cycle 1 Day 21, Cycle 2 Day 1, Cycle 2 Day 3, Cycle 2 Day 21 (Each cycle is 28 days)

Study Arms (6)

KLS-1 dose escalation Phase I - Cohort 1: 2.0 mg/kg

EXPERIMENTAL

3-6 patients will receive KLS-1 at 2.0 mg/kg.

Drug: Zinc-64 Aspartate

KLS-1 dose escalation Phase I - Cohort 2: 3.0 mg/kg

EXPERIMENTAL

3-6 patients will receive KLS-1 at 3.0 mg/kg.

Drug: Zinc-64 Aspartate

KLS-1 dose escalation Phase I - Cohort 3: 3.9 mg/kg

EXPERIMENTAL

3-6 patients will receive KLS-1 at 3.9 mg/kg.

Drug: Zinc-64 Aspartate

KLS-1 dose escalation Phase I - Cohort 4: 4.75 mg/kg

EXPERIMENTAL

3-6 patients will receive KLS-1 at 4.75 mg/kg.

Drug: Zinc-64 Aspartate

KLS-1 dose escalation Phase I - Cohort 5: 6.5 mg/kg

EXPERIMENTAL

3-6 patients will receive KLS-1 at 6.5 mg/kg.

Drug: Zinc-64 Aspartate

KLS-1 dose expansion Phase II cohort

EXPERIMENTAL

The Phase II dose (P2D) defined in Phase I will be administered in a dose expansion cohort during 5 weeks of continuous bi-weekly administration of KLS-1, demonstrating that this dose was well-tolerated and safe.

Drug: Zinc-64 Aspartate

Interventions

Zinc-64 Aspartate DRUG

KLS-1 drug substance is Zinc Aspartate enriched with isotope Zinc-64 to 99.2% mass fraction of total Zinc. KLS-1 investigational medicinal product (IMP) is formulated as a solution, containing 25.64 mg of drug substance in 1 ml and inactive ingredients (water for injections, USP, EuPh).

Also known as: KLS-1

KLS-1 dose escalation Phase I - Cohort 1: 2.0 mg/kg; KLS-1 dose escalation Phase I - Cohort 2: 3.0 mg/kg; KLS-1 dose escalation Phase I - Cohort 3: 3.9 mg/kg; KLS-1 dose escalation Phase I - Cohort 4: 4.75 mg/kg; KLS-1 dose escalation Phase I - Cohort 5: 6.5 mg/kg; KLS-1 dose expansion Phase II cohort

Eligibility Criteria

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

You may qualify if:

• Phase I and Phase II - solid tumors cohorts
• Adult (male or female) aged ≥18 years.
• Signed informed consent prior to any study-specific procedures.
• Patients who are willing to make themselves available for the duration of the study and are willing to follow study procedures.
• Have a performance status on the Eastern Cooperative Oncology Group (ECOG) scale of:
• Phase I - 0 or 1; Phase II - 0-2.
• Have an estimated life expectancy of ≥12 weeks.
• Have adequate organ function including:
• a. Hematologic:
• ANC ≥1.5 x 109/L
• Platelets ≥100 x 109/L
• Hemoglobin ≥90 g/L b. Hepatic:
• Albumin ≥30 g/L
• Bilirubin ≤1.5 times upper limit of normal (ULN)
• ALT and AST ≤2.5 x ULN. If the liver has tumor involvement, AST and ALT ≤5 x ULN are acceptable.

You may not qualify if:

• Have another tumor of another location except basal cell carcinoma.
• Have a history of organ transplant (e.g., heart, lungs, liver, bone marrow, or kidney).
• Females who are pregnant or breastfeeding.
• Have symptomatic human immunodeficiency virus (HIV) infection, known HIV positive test results or have chronic active hepatitis B or C (screening is not required).
• Positive COVID-19 test or signs of coronavirus infections.
• Have clinically significant cardiac disease including any of the following:
• A history of congenital long QT syndrome, symptomatic bradycardia, ventricular arrhythmia, uncontrolled atrial fibrillation, second- or third-degree heart block, or other conduction abnormality that in the opinion of the investigator would preclude safe participation in this study.
• Congestive heart failure (New York Heart Association Class ≥3).
• Unstable angina pectoris, acute myocardial infarction, or stroke ≤12 months prior to enrollment.
• QTcF prolongation \>450 msec.
• Currently taking medication known to prolong the QT interval or induce TdP, which cannot be discontinued or substituted.
• Uncontrolled type 1 or 2 diabetes with high risk of hypoglycemia.
• Are a family member of the investigator or staff of the study site.
• Are currently enrolled in another interventional clinical study of an investigational therapy.
• History of Richter's transformation or prolymphocytic leukemia.

Sponsors & Collaborators

• Vector Vitale LLC: lead

Study Sites (1)

Medical Centre of Arensia Exploratory Medicine LLC

Kyiv, 01135, Ukraine

RECRUITING

MeSH Terms

Conditions

Melanoma; Prostatic Neoplasms; Pancreatic Neoplasms; Leukemia, Lymphocytic, Chronic, B-Cell; Neoplasms; Neoplasm Metastasis

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases; Digestive System Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Leukemia, B-Cell; Leukemia, Lymphoid; Leukemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Study Officials

• Prof. Valerii Cheshuk, MD, PhD

  Medical Centre of Arensia Exploratory Medicine LLC

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Max Temnik

CONTACT

+1 305 331-12 13; clinicaltrials@vectorvitale.com

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: Phase I (a dose-escalation part) will explore multiple dose levels, pharmacokinetics (PK), and select a single dose level to explore in Phase II of the study. A conventional 3+3 design will be utilized. Once a dose level is selected, an additional cohort of 3-6 patients will be enrolled to assess more effectively the safety during 2 treatment cycles and confirm Phase II dose (P2D).

Study Record Dates

• First Submitted: June 7, 2024
• First Posted: July 17, 2024
• Study Start: May 15, 2024
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): October 31, 2026
• Last Updated: October 1, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

UA (1)