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IKS014 in Advanced Solid Tumors That Express HER2

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05872295
Recruitment Status : Recruiting
First Posted : May 24, 2023
Last Update Posted : September 21, 2023
Sponsor:
Information provided by (Responsible Party):
Iksuda Therapeutics Ltd.

Brief Summary:
This study will evaluate the recommended dose for further clinical development, safety, tolerability, anti-tumor activity, immunogenicity, pharmacokinetics and pharmacodynamics of IKS014, a HER2 targeting antibody-drug conjugate, in patients with advanced solid tumors.

Condition or disease Intervention/treatment Phase
Breast Cancer Gastric Cancer Gastroesophageal-junction Cancer Drug: IKS014 Phase 1

Detailed Description:
The study will consist of 2 parts: dose-escalation (Part 1) and dose-expansion (Part 2). The dose-escalation part (Part 1) of the study is to evaluate the safety and tolerability of increasing dose levels of IKS014 to establish a recommended phase 2 dose (RP2D); and the dose-expansion part (Part 2) of the study is to further evaluate the safety, pharmacokinetics/pharmacodynamics, and efficacy of IKS014 at the RP2D.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 165 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Dose Escalation Trial to Determine the Safety, Tolerance, Maximum Tolerated Dose, and Preliminary Antineoplastic Activity of IKS014, a HER2-Targeting Antibody Drug Conjugate (ADC), in Participants With Advanced HER2+ Solid Tumors
Actual Study Start Date : September 14, 2023
Estimated Primary Completion Date : September 2025
Estimated Study Completion Date : September 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Dose Escalation Cohort (Part 1)
Each patient will receive repeat doses (by intravenous (IV) infusions) on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Experimental: Dose Expansion: HER2+ Breast Cancer Participants
Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Experimental: Dose Expansion: HER2 Low Breast Cancer Participants
Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Experimental: Dose Expansion: HER2+ Gastric Cancer or Gastro-esophageal Junction Participants
Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Experimental: Dose Expansion: HER2 Low Gastric Cancer or Gastro-esophageal Junction Participants
Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Experimental: Dose Expansion: HER2 Solid Tumor Cancer Participants
Each patient will receive IKS014 at the recommended dose defined in Part 1 on Day 1 of each 21-day cycle. Participants may continue on study until disease progression, unacceptable toxicity, or other withdrawal criteria is met.
Drug: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.




Primary Outcome Measures :
  1. Recommended Phase 2 Dose (Part 1) [ Time Frame: Up to 24 months ]
    Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics

  2. Objective Response Rate (Part 2) [ Time Frame: Up to 24 months ]
    Anti-tumor activity will be assessed by RECIST 1.1


Secondary Outcome Measures :
  1. Objective Response Rate (Part 1) [ Time Frame: Up to 24 months ]
    Anti-tumor activity will be assessed by RECIST 1.1

  2. Plasma Concentrations of IKS014 (Part 1 and 2) [ Time Frame: Up to 48 months ]
    Pharmacokinetic parameters will be determined from observed concentrations of IKS014

  3. Evaluation of the immunogenicity of IKS014 (Part 1 and 2) [ Time Frame: Up to 48 months ]
    Occurrence of ADA measured in serum at selected timepoints during the study



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Key Inclusion Criteria:

  • HER2 positive solid tumors with expression defined as IHC3+, IHC2+/ISH+, or low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH- /+ or untested).
  • Participants with HR positive BC must have received prior treatment with a CDK4/6 inhibitor, in countries where this is standard therapy.
  • Platelets ≥ 75,000 /mcL
  • Hemoglobin ≥ 9.0 g/dL
  • Absolute neutrophil count ≥ 1000/mcL
  • No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 2 weeks prior to first study drug administration
  • Creatinine clearance > 45/mL/min (using the Cockcroft-Gault equation)
  • 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 if no liver metastases or < 3 x ULN with Gilbert's Syndrome or liver metastases at baseline
  • Albumin > 2.5 g/dL
  • Prothrombin time or international normalized ratio (INR) and either partial thromboplastin time (PTT) or activated (a) PTT ≤ 1.5 x ULN, ≤ 3 x institutional ULN if anticoagulated.
  • Must have adequate treatment washout period before trial treatment, defined as: Major surgery (≥ 4 weeks) and radiation therapy (≥ 3 weeks; in case of palliative radiation ≥ 2 weeks)
  • Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS)
  • Part 2 Dose Expansion Cohorts May Include:

    1. Advanced or metastatic BC that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH, as per ASCO-CAP and previously treated with at least two HER2 directed treatments.
    2. Advanced or metastatic BC that has low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH-/+ or untested) and previously treated with at least 1 prior line of therapy which may include chemotherapy and/or a HER2 directed ADC.
    3. Advanced or metastatic GC or GEJ cancer that is confirmed HER2-positive defined as IHC 3+ or IHC 2+ and evidence of HER2 amplification by ISH as per ASCO-CAP and previously treated with at least 1 prior line of therapy, which may include chemotherapy and/or a HER2 directed ADC.
    4. Advanced or metastatic GC or GEJ cancer that has low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH-/+ or untested) and has been previously treated with at least one prior line of therapy.
    5. Advanced or metastatic solid tumor that has any degree of HER2 expression (HER2 IHC3+, IHC2+, IHC1+ or ISH+) or a known activating HER2 mutation and has been treated with standard of care therapy relevant to the disease.

Key Exclusion Criteria:

  • History of (noninfectious) ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis cannot be ruled out by imaging at Screening.
  • Any clinically apparent ≥ Grade 2 pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (i.e., pulmonary emboli within three months of the trial enrollment, severe asthma, severe chronic obstructive pulmonary disease [COPD], restrictive lung disease, pleural effusion, etc.), and any autoimmune, connective tissue or inflammatory disorders with potential pulmonary involvement (e.g., rheumatoid arthritis, Sjogren's, sarcoidosis), or prior pneumonectomy.
  • Current evidence of ≥ Grade 2 keratitis or other corneal abnormality.
  • Evidence of a clinically significant (≥ Grade 2) abnormality on slit-lamp examination or other clinically significant ophthalmologic finding, as determined by an ophthalmologist.
  • Evidence of clinically significant (≥ Grade 2) confluent superficial keratitis, a corneal epithelial defect, a corneal ulcer, or stromal opacity.
  • Participant must not use contact lenses while participating in this study.
  • Central nervous system metastatic disease unless treated with definitive local therapy (surgical resection, stereotactic radiotherapy, or whole brain radiotherapy) and participant is clinically, radiologically and neurologically stable for at least 4 weeks prior to the first dose of study drug not on steroid therapy or are on a stable or decreasing dose of steroids for at least 7 days prior to first dose of study drug. Prophylactic anticonvulsant medications are allowed.
  • Active second malignancy or history of another malignancy within the last 2 years with the exception of:

    • Treated, non-melanoma skin cancers
    • Treated carcinoma in situ (CIS) (e.g., breast, cervix)
    • Controlled, superficial carcinoma of the urinary bladder
    • T1a or b carcinoma of the prostate treated according to local standard of care, with prostate specific antigen (PSA) within normal limits (WNL) for the institution
    • Papillary thyroid carcinoma Stage I treated surgically for cure
  • Clinically significant cardiovascular disease or condition
  • Clinically significant liver disease
  • Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first trial drug administration.
  • Any other serious, life-threatening, or unstable preexisting medical condition (aside from the underlying malignancy), including significant organ system dysfunction, or clinically significant laboratory abnormality(ies), which, in the opinion of the Investigator, would either compromise the participant's safety or interfere with obtaining informed consent, compliance with trial procedures, or evaluation of the safety of the trial drug

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05872295


Contacts
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Contact: David Browning +1-615-975-7776 david.browning@iksuda.com

Locations
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Australia, New South Wales
Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit Not yet recruiting
Concord, New South Wales, Australia, 2139
Contact: Tam Bui, MD    (02) 9767 5988      
Principal Investigator: Tam Bui, MD         
Westmead Hospital Not yet recruiting
Westmead, New South Wales, Australia, 2145
Contact: Adnan Nagrial, MD    0403170371      
Principal Investigator: Adnan Nagrial, MD         
Australia, Victoria
Peninsula & South Eastern Haematology and Oncology Group (PSEHOG) Recruiting
Frankston, Victoria, Australia, 3199
Contact: Vinod Ganju, MD    0397815244      
Principal Investigator: Vinod Ganju, MD         
Alfred Health Not yet recruiting
Melbourne, Victoria, Australia, 3004
Contact: Malaka Ameratunga, MD    0390763129      
Principal Investigator: Malaka Ameratunga, MD         
Australia, Western Australia
Linear Clinical Research Recruiting
Nedlands, Western Australia, Australia, 6009
Contact: Peter Lau, MD    0438899188      
Principal Investigator: Peter Lau, MD         
Sponsors and Collaborators
Iksuda Therapeutics Ltd.
Investigators
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Study Director: James O'Leary, MD Iksuda Therapeutics
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Responsible Party: Iksuda Therapeutics Ltd.
ClinicalTrials.gov Identifier: NCT05872295    
Other Study ID Numbers: IKS014-01
First Posted: May 24, 2023    Key Record Dates
Last Update Posted: September 21, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Iksuda Therapeutics Ltd.:
HER2
IKS014
Low HER2
Advanced tumors
HER2+
HER2-positive
HER2 expression
GEJ
Additional relevant MeSH terms:
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Stomach Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Stomach Diseases