IKS014 in Advanced Solid Tumors That Express HER2

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

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.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Gastric Cancer; Gastroesophageal-junction Cancer
• Intervention / Treatment: Drug: IKS014

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.

• Study Type: Interventional
• Enrollment (Estimated): 165
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: David Browning; Phone Number: +1-615-975-7776; Email: david.browning@iksuda.com

Study Locations

• Australia
  • New South Wales
    • Concord, New South Wales, Australia, 2139
      • Recruiting
      • Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit
      • Contact: Tam Bui, MD; Phone Number: (02) 9767 5988
      • Principal Investigator: Tam Bui, MD
    • Westmead, New South Wales, Australia, 2145
      • Recruiting
      • Westmead Hospital
      • Principal Investigator: Adnan Nagrial, MD
      • Contact: Adnan Nagrial, MD; Phone Number: 0403170371
  • Victoria
    • Frankston, Victoria, Australia, 3199
      • Recruiting
      • Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)
      • Principal Investigator: Vinod Ganju, MD
      • Contact: Vinod Ganju, MD; Phone Number: 0397815244
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Health
      • Principal Investigator: Malaka Ameratunga, MD
      • Contact: Malaka Ameratunga, MD; Phone Number: 0390763129
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research
      • Principal Investigator: Peter Lau, MD
      • Contact: Peter Lau, MD; Phone Number: 0438899188

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recommended Phase 2 Dose (Part 1)	Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics	Up to 24 months
Objective Response Rate (Part 2)	Anti-tumor activity will be assessed by RECIST 1.1	Up to 24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (Part 1)	Anti-tumor activity will be assessed by RECIST 1.1	Up to 24 months
Plasma Concentrations of IKS014 (Part 1 and 2)	Pharmacokinetic parameters will be determined from observed concentrations of IKS014	Up to 48 months
Evaluation of the immunogenicity of IKS014 (Part 1 and 2)	Occurrence of ADA measured in serum at selected timepoints during the study	Up to 48 months

Collaborators and Investigators

• Sponsor: Iksuda Therapeutics Ltd.
• Investigators: Study Director: James O'Leary, MD, Iksuda Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): September 14, 2023
• Primary Completion (Estimated): September 1, 2025
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: May 14, 2023
• First Submitted That Met QC Criteria: May 14, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): December 18, 2023
• Last Update Submitted That Met QC Criteria: December 15, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: HER2; HER2-positive; HER2+; Advanced tumors; GEJ; HER2 expression; IKS014; Low HER2
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: IKS014-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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