Trial Review

Registering a new trial?

To achieve prospective registration, we recommend submitting your trial for registration at the same time as ethics submission.

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 endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05872295




Registration number
NCT05872295
Ethics application status
Date submitted
14/05/2023
Date registered
24/05/2023
Date last updated
18/12/2023

Titles & IDs
Public title
IKS014 in Advanced Solid Tumors That Express HER2
Scientific 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
Secondary ID [1] 0 0
IKS014-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Breast Cancer 0 0
Gastric Cancer 0 0
Gastroesophageal-junction Cancer 0 0
Condition category
Condition code
Cancer 0 0 0 0
Stomach

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IKS014

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.

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.

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.

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.

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.

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.


Treatment: Drugs: IKS014
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Recommended Phase 2 Dose (Part 1)
Timepoint [1] 0 0
Up to 24 months
Primary outcome [2] 0 0
Objective Response Rate (Part 2)
Timepoint [2] 0 0
Up to 24 months
Secondary outcome [1] 0 0
Objective Response Rate (Part 1)
Timepoint [1] 0 0
Up to 24 months
Secondary outcome [2] 0 0
Plasma Concentrations of IKS014 (Part 1 and 2)
Timepoint [2] 0 0
Up to 48 months
Secondary outcome [3] 0 0
Evaluation of the immunogenicity of IKS014 (Part 1 and 2)
Timepoint [3] 0 0
Up to 48 months

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
14/09/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2027
Actual
Sample size
Target
165
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,VIC,WA
Recruitment hospital [1] 0 0
Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit - Concord
Recruitment hospital [2] 0 0
Westmead Hospital - Westmead
Recruitment hospital [3] 0 0
Peninsula & South Eastern Haematology and Oncology Group (PSEHOG) - Frankston
Recruitment hospital [4] 0 0
Alfred Health - Melbourne
Recruitment hospital [5] 0 0
Linear Clinical Research - Nedlands
Recruitment postcode(s) [1] 0 0
2139 - Concord
Recruitment postcode(s) [2] 0 0
2145 - Westmead
Recruitment postcode(s) [3] 0 0
3199 - Frankston
Recruitment postcode(s) [4] 0 0
3004 - Melbourne
Recruitment postcode(s) [5] 0 0
6009 - Nedlands

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Iksuda Therapeutics Ltd.
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05872295
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
James O'Leary, MD
Address 0 0
Iksuda Therapeutics
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
David Browning
Address 0 0
Country 0 0
Phone 0 0
+1-615-975-7776
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05872295