Trial Title:
IKS014 in Advanced Solid Tumors That Express HER2
NCT ID:
NCT05872295
Condition:
Breast Cancer
Gastric Cancer
Gastroesophageal-junction Cancer
Conditions: Official terms:
Stomach Neoplasms
Conditions: Keywords:
HER2
IKS014
Low HER2
Advanced tumors
HER2+
HER2-positive
HER2 expression
GEJ
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Recruiting
Study design:
Allocation:
Non-Randomized
Intervention model:
Sequential Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
IKS014
Description:
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin
F (MMAF) cytotoxic agent.
Arm group label:
Dose Escalation Cohort (Part 1)
Arm group label:
Dose Expansion: HER2 Low Breast Cancer Participants
Arm group label:
Dose Expansion: HER2 Low Gastric Cancer or Gastro-esophageal Junction Participants
Arm group label:
Dose Expansion: HER2 Solid Tumor Cancer Participants
Arm group label:
Dose Expansion: HER2+ Breast Cancer Participants
Arm group label:
Dose Expansion: HER2+ Gastric Cancer or Gastro-esophageal Junction Participants
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.
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.
Criteria for eligibility:
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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit
Address:
City:
Concord
Zip:
2139
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Tam Bui, MD
Phone:
(02) 9767 5988
Investigator:
Last name:
Tam Bui, MD
Email:
Principal Investigator
Facility:
Name:
Westmead Hospital
Address:
City:
Westmead
Zip:
2145
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Adnan Nagrial, MD
Phone:
0403170371
Investigator:
Last name:
Adnan Nagrial, MD
Email:
Principal Investigator
Facility:
Name:
Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)
Address:
City:
Frankston
Zip:
3199
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Vinod Ganju, MD
Phone:
0397815244
Investigator:
Last name:
Vinod Ganju, MD
Email:
Principal Investigator
Facility:
Name:
Alfred Health
Address:
City:
Melbourne
Zip:
3004
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Malaka Ameratunga, MD
Phone:
0390763129
Investigator:
Last name:
Malaka Ameratunga, MD
Email:
Principal Investigator
Facility:
Name:
Linear Clinical Research
Address:
City:
Nedlands
Zip:
6009
Country:
Australia
Status:
Recruiting
Contact:
Last name:
Peter Lau, MD
Phone:
0438899188
Investigator:
Last name:
Peter Lau, MD
Email:
Principal Investigator
Start date:
September 14, 2023
Completion date:
September 2027
Lead sponsor:
Agency:
Iksuda Therapeutics Ltd.
Agency class:
Industry
Source:
Iksuda Therapeutics Ltd.
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05872295
