IKS014 v pokročilých solidních nádorech, které vyjadřují HER2
Fáze 1 studie eskalace dávky k určení bezpečnosti, tolerance, maximální tolerované dávky a předběžné antineoplastické aktivity IKS014, konjugátu s protilátkou cílenou na HER2 (ADC), u účastníků s pokročilými HER2+ pevnými nádory
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.
Přehled studie
Postavení
Postavení
Podmínky
Podmínky
Intervence / Léčba
Intervence / Léčba
Detailní popis
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.
Typ studie
Typ studie
Zápis (Odhadovaný)
Zápis
Fáze
Fáze
- Fáze 1
Kontakty a umístění
Studijní kontakt
Studijní kontakt
- Jméno: David Browning
- Telefonní číslo: +1-615-975-7776
- E-mail: david.browning@iksuda.com
Studijní místa
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New South Wales
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Concord, New South Wales, Austrálie, 2139
- Nábor
- Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit
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Vrchní vyšetřovatel:
- Tam Bui, MD
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Sydney, New South Wales, Austrálie, 2109
- Nábor
- Macquarie University
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Vrchní vyšetřovatel:
- Dhanusha Sabanathan, MD
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Westmead, New South Wales, Austrálie, 2145
- Nábor
- Westmead Hospital
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Vrchní vyšetřovatel:
- Adnan Nagrial, MD
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Victoria
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Frankston, Victoria, Austrálie, 3199
- Nábor
- Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)
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Vrchní vyšetřovatel:
- Vinod Ganju, MD
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Melbourne, Victoria, Austrálie, 3004
- Nábor
- Alfred Health
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Vrchní vyšetřovatel:
- Malaka Ameratunga, MD
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Western Australia
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Nedlands, Western Australia, Austrálie, 6009
- Nábor
- Linear Clinical Research
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Vrchní vyšetřovatel:
- Peter Lau, MD
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Auckland, Nový Zéland
- Nábor
- Auckland City Hospital
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Vrchní vyšetřovatel:
- Jane So, MBChB
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Singapore, Singapur
- Nábor
- National Cancer Centre Singapore
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Vrchní vyšetřovatel:
- Jing Ying Tira Tan, MBBS
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Singapore, Singapur
- Nábor
- Tan Tock Seng Hospital
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Vrchní vyšetřovatel:
- Yue Ming Valerie Heong, MBBS
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California
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Newport Beach, California, Spojené státy, 92663
- Nábor
- Hoag Memorial Hospital Presbyterian
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Vrchní vyšetřovatel:
- Monica Mita, MD
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Massachusetts
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Boston, Massachusetts, Spojené státy, 02215
- Nábor
- Dana Farber Cancer Institute
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Vrchní vyšetřovatel:
- Nancy Lin, MD
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Tennessee
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Nashville, Tennessee, Spojené státy, 37203
- Nábor
- Tennessee Oncology
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Vrchní vyšetřovatel:
- Jeffrey Russell, MD
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Texas
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Fort Worth, Texas, Spojené státy, 76104
- Nábor
- START Dallas - Fort Worth
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Vrchní vyšetřovatel:
- Henry Xiong, MD
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Kontakt:
- Hope Team
- E-mail: hopeteam@startresearch.com
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Kritéria účasti
Kritéria způsobilosti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Popis
Key Inclusion Criteria:
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HER2 positive solid tumors with expression defined as IHC3+, IHC2+/ISH+, or low HER2 expression defined as IHC2+ (ISH-) or IHC1+ (ISH- /+ or untested).
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Participants with HR positive BC must have received prior treatment with a CDK4/6 inhibitor, in countries where this is standard therapy.
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Platelets ≥ 75,000 /mcL
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Hemoglobin ≥ 9.0 g/dL
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Absolute neutrophil count ≥ 1000/mcL
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No administration of granulocyte colony-stimulating factor (G-CSF) is allowed within 2 weeks prior to first study drug administration
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Creatinine clearance > 45/mL/min (using the Cockcroft-Gault equation)
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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
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Total bilirubin ≤ 1.5 x ULN if no liver metastases or < 3 x ULN with Gilbert's Syndrome or liver metastases at baseline
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Albumin > 2.5 g/dL
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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.
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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)
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Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS)
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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.
- 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.
- 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.
- Advanced or metastatic solid tumor that has been treated with standard of care therapy and is HER2 positive (HER2 IHC3+) as per ASCO-CAP or metastatic NSCLC (that has been treated with standard of care therapy) with a known activating HER2 (ERBB2) mutation.
- Advanced or metastatic adenocarcinoma of the Esophagus that has been treated with at least one prior line of standard treatment, which may have included a HER2-directed therapy. The tumor must be HER2 positive defined either HER2 IHC3+ or HER2 IHC 2+/ISH+.
Key Exclusion Criteria:
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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.
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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.
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Current evidence of ≥ Grade 2 keratitis or other corneal abnormality.
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Evidence of a clinically significant (≥ Grade 2) abnormality on slit-lamp examination or other clinically significant ophthalmologic finding, as determined by an ophthalmologist.
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Evidence of clinically significant (≥ Grade 2) confluent superficial keratitis, a corneal epithelial defect, a corneal ulcer, or stromal opacity.
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Participant must not use contact lenses while participating in this study.
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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.
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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
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Clinically significant cardiovascular disease or condition
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Clinically significant liver disease
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Any other serious/active/uncontrolled infection, any infection requiring parenteral antibiotics, or unexplained fever > 38ºC within 2 weeks prior to first trial drug administration.
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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.
Studijní plán
Jak je studie koncipována?
Detaily designu
- Primární účel: Léčba
- Přidělení: Nerandomizované
- Intervenční model: Sekvenční přiřazení
- Maskování: Žádné (otevřený štítek)
Počet zbraní
Zbraně a zásahy
Skupina účastníků / ArmSkupina účastníků / Arm |
Intervence / LéčbaIntervence / Léčba |
|---|---|
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Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
|
Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
|
Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
|
Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
|
Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
|
Experimentální: 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. |
IKS014 is a human monoclonal antibody (Ab) targeting HER2 linked to monomethyl auristatin F (MMAF) cytotoxic agent. |
Co je měření studie?
Primární výstupní opatření
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Recommended Phase 2 Dose (Part 1)
Časové okno: Up to 24 months
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Based on tolerability, preliminary anti-tumor activity, and pharmacokinetics |
Up to 24 months
|
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Objective Response Rate (Part 2)
Časové okno: Up to 24 months
|
Anti-tumor activity will be assessed by RECIST 1.1 |
Up to 24 months
|
Sekundární výstupní opatření
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Objective Response Rate (Part 1)
Časové okno: Up to 24 months
|
Anti-tumor activity will be assessed by RECIST 1.1 |
Up to 24 months
|
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Plasma Concentrations of IKS014 (Part 1 and 2)
Časové okno: Up to 48 months
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Pharmacokinetic parameters will be determined from observed concentrations of IKS014 |
Up to 48 months
|
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Evaluation of the immunogenicity of IKS014 (Part 1 and 2)
Časové okno: Up to 48 months
|
Occurrence of ADA measured in serum at selected timepoints during the study |
Up to 48 months
|
Spolupracovníci a vyšetřovatelé
Sponzor
Sponzor
Vyšetřovatelé
Vyšetřovatelé
- Ředitel studie: James O'Leary, MD, Iksuda Therapeutics
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Aktuální)
Začátek studia
Primární dokončení (Odhadovaný)
Primární dokončení
Dokončení studie (Odhadovaný)
Dokončení studie
Termíny zápisu do studia
První předloženo
První předloženo
První předloženo, které splnilo kritéria kontroly kvality
První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
První zveřejněno
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
Poslední zveřejněná aktualizace
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
Naposledy ověřeno
Naposledy ověřeno
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
Další identifikační čísla studie
- IKS014-01
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Studuje produkt zařízení regulovaný americkým úřadem FDA
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