Biliary Tract Cancer (BTC), Cholangiocarcinoma, Colorectal Cancer, Gall Bladder Cancer, Gastric Cancer (GC), Gastro Esophageal Junctional Cancer, GEJ Adenocarcinoma, PDAC - Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
CA242, advanced gastrointestinal tumors, IKS04, Isumab04
Brief 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.
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
DRUGIKS04 antibody drug conjugate ADC + Isumab04 monoclonal antibody
IKS04 Regimen \[Isumab04 (the antibody component of IKS04) followed by IKS04 ADC\]
Sponsors
Iksuda Therapeutics Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose (Part I) | Up to 24 months | Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics |
| Objective Response Rate (Part II) | Up to 24 months | Anti-tumor activity will be assessed by RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate | Up to 24 months | Anti-tumor activity will be assessed by RECIST 1.1 |
| Maximum Concentration (Cmax) (Part I and II) | Up to 48 months | Cmax of total ADC, total antibody and unconjugated payload will be measured. |
| Area under the plasma concentration versus time curve (AUC) (Part I and II) | 48 months | AUC of total ADC, total antibody and unconjugated payload will be measured. |
| Half-life (T1/2) (Part I and II) | 48 months | Half-life (T1/2) of total ADC, total antibody and unconjugated payload will be measured. |
| Evaluation of Immunogenicity of IKS04 Regimen (Part I and II) | Up to 48 months | Occurrence of ADA measured in serum at selected timepoints during the study |
Countries
United States
Contacts
CONTACTDavid Browning
STUDY_DIRECTORJames O'Leary, MD
Iksuda Therapeutics Ltd.
Outcome results
None listed