IKS04 Regimen in Advanced Solid Tumors That Express CA242

Summary

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.

Interventions

• IKS04 antibody drug conjugate ADC + Isumab04 monoclonal antibody · DRUG

  IKS04 Regimen \[Isumab04 (the antibody component of IKS04) followed by IKS04 ADC\]

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

Key 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

Key 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

Sites (4)

• UCLA Medical Center, Los Angeles, California
• Mass General Hospital, Boston, Massachusetts
• Vanderbilt University Medical Center, Nashville, Tennessee
• MD Anderson Cancer Center, Houston, Texas