IKS04 Regimen in Advanced Solid Tumors That Express CA242

Official title

A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of the IKS04 Regimen Targeting CA242

Overview

This study will evaluate the safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of the IKS04 Regimen and identify a recommended phase 2 dose (RP2D) or recommended dose for further evaluation in expansion (RDE). The regimen includes Isumab04 (unconjugated antibody) followed by the IKS04 antibody-drug conjugate, both directed against the CA242 (CanAg) tumor-associated antigen and administered intravenously (IV) in patients with advanced solid cancers.

Detailed description

The study will consist of 2 parts: dose-escalation (Part I) and dose-expansion (Part II). The dose-escalation part (Part I) will evaluate the safety and tolerability of increasing dose levels of the IKS04 Regimen and to establish a RP2D and/or a RDE; and the dose-expansion portion (Part II) of the study will further characterize the safety, pharmacokinetics/pharmacodynamics, and efficacy of the IKS04 Regimen at the RP2D or RDE. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.

Interventions

• Drug IKS04 antibody drug conjugate ADC + Isumab04 monoclonal antibody
  IKS04 Regimen \[Isumab04 (the antibody component of IKS04) followed by IKS04 ADC\]

Primary outcome measures

• Recommended Phase 2 Dose (Part I) [Time frame: Up to 24 months]
• Objective Response Rate (Part II) [Time frame: Up to 24 months]

Secondary outcome measures (5)

• Objective Response Rate [Time frame: Up to 24 months]
• Maximum Concentration (Cmax) (Part I and II) [Time frame: Up to 48 months]
• Area under the plasma concentration versus time curve (AUC) (Part I and II) [Time frame: 48 months]
• Half-life (T1/2) (Part I and II) [Time frame: 48 months]
• Evaluation of Immunogenicity of IKS04 Regimen (Part I and II) [Time frame: Up to 48 months]

Eligibility criteria

Inclusion criteria

• Advanced or metastatic CRC, BTCs, GEA, and PDAC that is histologically or cytologically confirmed
• Disease that has progressed despite prior treatment, for which additional effective therapy is not available, not tolerable, is contraindicated, or the participant refuses standard therapy.
• Platelets ≥ 100,000 /mcL
• Hemoglobin ≥ 9.0 g/dL., no transfusions with RBCs are allowed within 2 weeks prior to first trial drug administration
• ANC ≥ 1500/mcL
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) ≤ 3 x institutional upper limit of normal (ULN) ≤ 5 x ULN if liver metastases present
• Total bilirubin ≤ 1.5 x ULN, unless participant has Gilbert's Syndrome
• Albumin > 2.5 g/dL
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1

Part I

• Fresh biopsy tissue or formalin-fixed paraffin-embedded (FFPE) tumor tissue block or slides available for retrospective assessment of CA242 positivity in a central laboratory.
• Measurable and non-measurable disease

Part II

• Fresh biopsy tissue or FFPE tumor tissue block or slides for assessment of CA242 positivity in a central laboratory prior to administration of first dose of study drug.
• Measurable disease only

Exclusion criteria

• Participants with a significant pulmonary disease or condition, including:

• Significant symptomatic chronic obstructive pulmonary disease (COPD), as assessed by the Investigator.
• History or any current evidence on imaging studies of interstitial lung disease (ILD), pulmonary fibrosis.
• History of pulmonary inflammatory disease, pneumonitis, acute respiratory distress syndrome (ARDS).
• History of pneumonia within 3 months prior to the first trial drug administration.
• Participants who have received previous treatment with any CA242 directed ADC or any ADC containing a PBD payload for their current tumor indication.
• Participant may not have received more than 5 prior lines of systemic therapy.
• Received treatment with a strong cytochrome P450 (CYP) 3A4 inhibitor within 7 days or 5 half-lives (whichever is longer) prior to the first trial drug administration
• Central nervous system metastatic disease unless treated prior to first dose of trial drug.
• Active second malignancy or history of another malignancy within the last 2 years with specific exceptions as per protocol
• Active, known or suspected autoimmune disease, or a documented history of autoimmune disease or syndrome requiring systemic steroids or other immunosuppressive medications, such as:

• Myocarditis, pneumonitis, glomerulonephritis.
• Autoimmune hepatitis, inflammatory bowel disease (IBD)
• Sjogren's syndrome
• Rheumatoid arthritis (RA), systemic lupus erythematosus (SLE)
• Myositis
• Myasthenia gravis
• Guillain-Barré Syndrome
• Multiple sclerosis
• Granulomatosis with polyangiitis (Wegner's granulomatosis)
• Vasculitis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 4 centers

• UCLA Medical Center — Los Angeles
• Mass General Hospital — Boston
• Vanderbilt University Medical Center — Nashville
• MD Anderson Cancer Center — Houston

Identifiers

NCT: NCT07738939 · IKS04-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗