HER2를 발현하는 진행성 고형 종양의 IKS014
진행성 HER2+ 고형 종양 환자에서 HER2 표적 항체 약물 접합체(ADC)인 IKS014의 안전성, 내성, 최대 허용 용량 및 예비 항종양 활성을 결정하기 위한 1상 용량 증량 시험
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.
연구 개요
상태
상태
정황
정황
개입 / 치료
개입 / 치료
상세 설명
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.
연구 유형
연구 유형
등록 (추정된)
등록
단계
단계
- 1단계
연락처 및 위치
연구 연락처
연구 연락처
- 이름: David Browning
- 전화번호: +1-615-975-7776
- 이메일: david.browning@iksuda.com
연구 장소
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Auckland, 뉴질랜드
- 모병
- Auckland City Hospital
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수석 연구원:
- Jane So, MBChB
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California
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Newport Beach, California, 미국, 92663
- 모병
- Hoag Memorial Hospital Presbyterian
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수석 연구원:
- Monica Mita, MD
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Massachusetts
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Boston, Massachusetts, 미국, 02215
- 모병
- Dana Farber Cancer Institute
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수석 연구원:
- Nancy Lin, MD
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Tennessee
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Nashville, Tennessee, 미국, 37203
- 모병
- Tennessee Oncology
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수석 연구원:
- Jeffrey Russell, MD
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Texas
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Fort Worth, Texas, 미국, 76104
- 모병
- START Dallas - Fort Worth
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수석 연구원:
- Henry Xiong, MD
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연락하다:
- Hope Team
- 이메일: hopeteam@startresearch.com
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Singapore, 싱가포르
- 모병
- National Cancer Centre Singapore
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수석 연구원:
- Jing Ying Tira Tan, MBBS
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Singapore, 싱가포르
- 모병
- Tan Tock Seng Hospital
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수석 연구원:
- Yue Ming Valerie Heong, MBBS
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New South Wales
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Concord, New South Wales, 호주, 2139
- 모병
- Concord Repatriation General Hospital Medical Oncology Clinical Trials Unit
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수석 연구원:
- Tam Bui, MD
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Sydney, New South Wales, 호주, 2109
- 모병
- Macquarie University
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수석 연구원:
- Dhanusha Sabanathan, MD
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Westmead, New South Wales, 호주, 2145
- 모병
- Westmead Hospital
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수석 연구원:
- Adnan Nagrial, MD
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Victoria
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Frankston, Victoria, 호주, 3199
- 모병
- Peninsula & South Eastern Haematology and Oncology Group (PSEHOG)
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수석 연구원:
- Vinod Ganju, MD
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Melbourne, Victoria, 호주, 3004
- 모병
- Alfred Health
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수석 연구원:
- Malaka Ameratunga, MD
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Western Australia
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Nedlands, Western Australia, 호주, 6009
- 모병
- Linear Clinical Research
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수석 연구원:
- Peter Lau, MD
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참여기준
자격 기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
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.
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위화되지 않음
- 중재 모델: 순차적 할당
- 마스킹: 없음(오픈 라벨)
팔의 수
무기와 개입
참가자 그룹 / 팔참가자 그룹 / 팔 |
개입 / 치료개입 / 치료 |
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실험적: 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. |
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실험적: 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. |
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실험적: 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. |
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실험적: 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. |
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실험적: 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. |
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실험적: 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. |
연구는 무엇을 측정합니까?
주요 결과 측정
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Recommended Phase 2 Dose (Part 1)
기간: 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)
기간: Up to 24 months
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Anti-tumor activity will be assessed by RECIST 1.1 |
Up to 24 months
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2차 결과 측정
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Objective Response Rate (Part 1)
기간: Up to 24 months
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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)
기간: 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)
기간: Up to 48 months
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Occurrence of ADA measured in serum at selected timepoints during the study |
Up to 48 months
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공동 작업자 및 조사자
수사관
수사관
- 연구 책임자: James O'Leary, MD, Iksuda Therapeutics
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
연구 시작
기본 완료 (추정된)
기본 완료
연구 완료 (추정된)
연구 완료
연구 등록 날짜
최초 제출
최초 제출
QC 기준을 충족하는 최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (실제)
처음 게시됨
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
마지막 업데이트 게시됨
QC 기준을 충족하는 마지막 업데이트 제출
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
마지막으로 확인됨
추가 정보
이 연구와 관련된 용어
기타 연구 ID 번호
기타 연구 ID 번호
- IKS014-01
개별 참가자 데이터(IPD) 계획
개별 참가자 데이터(IPD)를 공유할 계획입니까?
약물 및 장치 정보, 연구 문서
미국 FDA 규제 의약품 연구
미국 FDA 규제 기기 제품 연구
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