IKS014 in Advanced Solid Tumors That Express HER2

NCT05872295 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IKS014-01
• Study Type: interventional
• Target: 165
• Locations: 4 countries
• Sites: 12

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.

Conditions

Breast Cancer; Gastric Cancer; Gastroesophageal-junction Cancer

Keywords

HER2; IKS014; Low HER2; Advanced tumors; HER2+; HER2-positive; HER2 expression; GEJ

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (3)

• Objective Response Rate (Part 1)

  Up to 24 months

• Plasma Concentrations of IKS014 (Part 1 and 2)

  Up to 48 months

• Evaluation of the immunogenicity of IKS014 (Part 1 and 2)

  Up to 48 months

Study Arms (6)

Dose Escalation Cohort (Part 1)

EXPERIMENTAL

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

Dose Expansion: HER2+ Breast Cancer Participants

EXPERIMENTAL

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

Dose Expansion: HER2 Low Breast Cancer Participants

EXPERIMENTAL

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

Dose Expansion: HER2+ Gastric Cancer or Gastro-esophageal Junction Participants

EXPERIMENTAL

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

Dose Expansion: HER2 Low Gastric Cancer or Gastro-esophageal Junction Participants

EXPERIMENTAL

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

Dose Expansion: HER2 Solid Tumor Cancer Participants

EXPERIMENTAL

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

Interventions

IKS014 DRUG

IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.

Dose Escalation Cohort (Part 1); Dose Expansion: HER2 Low Breast Cancer Participants; Dose Expansion: HER2 Low Gastric Cancer or Gastro-esophageal Junction Participants; Dose Expansion: HER2 Solid Tumor Cancer Participants; Dose Expansion: HER2+ Breast Cancer Participants; Dose Expansion: HER2+ Gastric Cancer or Gastro-esophageal Junction Participants

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Iksuda Therapeutics Ltd.: lead

Study Sites (12)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663, United States

RECRUITING

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit

Concord, New South Wales, 2139, Australia

RECRUITING

Macquarie University

Sydney, New South Wales, 2109, Australia

RECRUITING

Westmead Hospital

Westmead, New South Wales, 2145, Australia

RECRUITING

Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)

Frankston, Victoria, 3199, Australia

RECRUITING

Alfred Health

Melbourne, Victoria, 3004, Australia

RECRUITING

Linear Clinical Research

Nedlands, Western Australia, 6009, Australia

RECRUITING

Auckland City Hospital

Auckland, New Zealand

RECRUITING

National Cancer Centre Singapore

Singapore, Singapore

RECRUITING

Tan Tock Seng Hospital

Singapore, Singapore

RECRUITING

MeSH Terms

Conditions

Breast Neoplasms; Stomach Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Study Officials

• James O'Leary, MD

  Iksuda Therapeutics

  STUDY DIRECTOR

Central Study Contacts

David Browning

CONTACT

+1-615-975-7776; david.browning@iksuda.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2023
• First Posted: May 24, 2023
• Study Start: September 14, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: January 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

SG (2); NZ (1); AU (6); US (3)