RECRUITING

IKS014 in Advanced Solid Tumors That Express HER2

Conditions

Breast Cancer Gastric Cancer Gastroesophageal-junction Cancer HER2 IKS014 Low HER2 Advanced tumors HER2+HER2-positive HER2 expression GEJ

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

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

Quick Facts

Study Start:2023-09-14

Study Completion:2027-09

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05872295

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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.	* 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

Inclusion Criteria

Exclusion 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.

* 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

Contacts and Locations

Study Contact

David Browning

CONTACT

+1-615-975-7776

david.browning@iksuda.com

Principal Investigator

James O'Leary, MD

STUDY_DIRECTOR

Iksuda Therapeutics

Study Locations (Sites)

Hoag Memorial Hospital Presbyterian

Newport Beach, California, 92663

United States

Dana Farber Cancer Institute

Boston, Massachusetts, 02215

United States

Tennessee Oncology

Nashville, Tennessee, 37203

United States

Collaborators and Investigators

Sponsor: Iksuda Therapeutics Ltd.

James O'Leary, MD, STUDY_DIRECTOR, Iksuda Therapeutics

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-14

Study Completion Date2027-09

Study Record Updates

Study Start Date2023-09-14

Study Completion Date2027-09

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Breast Cancer
Gastric Cancer
Gastroesophageal-junction Cancer