A Study of Disitamab Vedotin Alone or With Other Anticancer Drugs in Solid Tumors

Registration Number
NCT06157892
Lead Sponsor
Seagen Inc.
Brief Summary

This clinical trial is studying solid tumor cancers. A solid tumor is one that starts in part of your body like your lungs or liver instead of your blood. Once they've grown bigger in one spot or spread to other parts of the body, they're harder to treat. This is called advanced or metastatic cancer.
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Detailed Description

This clinical trial is to evaluate disitamab vedotin alone and in combination with tucatinib in subjects with LA/metastatic breast cancer or gastric cancer/GEJC that express HER2. The study has a dose escalation phase evaluating disitamab vedotin plus tucatinib followed by a dose optimization phase. The 2 dose levels identified in the dose escalation phase w...

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
198
Inclusion Criteria

General Inclusion Criteria

  • Measurable disease according to RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1

Dose Escalation Phase Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
  • Locally-advanced, unresectable, or metastatic stage
  • HER2 status IHC 1+ or higher by most recent local assessment.
  • Must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies.

Cohort A (HER2-Low Breast Cancer) Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of breast carcinoma

  • Locally-advanced, unresectable, or metastatic stage

  • HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH-negative)

  • Prior therapies requirements

    • No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC.

    • Participants with known BRCA mutation must have received a PARP-inhibitor where available and not medically contraindicated

    • Have progression on or after, or intolerant to, T-DXd, sacituzumab govitecan, or other topoisomerase I inhibitor therapies, if available as local standard of care therapy

    • Participants with HR+ tumors must have endocrine therapy refractory disease:

      • Progressed on ≥2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR
      • Progressed on 1 line of endocrine therapy for LA/mBC AND had a relapse while on adjuvant endocrine therapy after definitive surgery for primary tumor AND had received a CDK4/6 inhibitor in the adjuvant or advanced setting
    • Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab with chemotherapy if available as local standard of care therapy.

Cohort B (HER2+ Breast Cancer) Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis breast carcinoma

  • Locally-advanced, unresectable, or metastatic stage

  • HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)

  • Participants must have:

    • Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy.
    • Have progression on or after, or intolerant to, T-DXd or other topoisomerase I inhibitor therapies
    • No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC

Cohort C (HER2-Low Gastric or Gastroesophageal Junction Adenocarcinoma) Inclusion Criteria

  • Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma

  • Locally-advanced, unresectable, or metastatic stage

  • HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment

  • Willing and able to provide archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks

  • Participants must have received:

    • Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease
    • Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC
    • Prior anti-PD-(L)1 therapy is allowed
    • No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC
  • Must not have received prior treatment with HER2 directed therapy

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Exclusion Criteria
  • Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib
  • Prior therapy with ADCs with MMAE payload
  • Prior therapy with tucatinib
  • Active CNS and/or leptomeningeal metastasis.
  • Participants who have received prior systemic anticancer treatment including investigational agents within 4 weeks prior to first dose of study treatment
  • History of other invasive malignancy within 3 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
  • Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications
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Study & Design

Study Type
INTERVENTIONAL
Study Design
SEQUENTIAL
Arm && Interventions
GroupInterventionDescription
Dose Escalation - Previously treated advanced GC/GEJC or breast cancerdisitamab vedotindisitamab vedotin + tucatinib
Dose Escalation - Previously treated advanced GC/GEJC or breast cancertucatinibdisitamab vedotin + tucatinib
Cohort A monotherapy - HER2-low 2L or 3L breast cancerdisitamab vedotindisitamab vedotin monotherapy
Cohort A - HER2-low 2L or 3L breast cancertucatinibdisitamab vedotin + tucatinib
Cohort B - HER2+ 3L or higher breast cancertucatinibdisitamab vedotin + tucatinib
Cohort C monotherapy - HER2-low 2L GC/GEJCdisitamab vedotindisitamab vedotin monotherapy
Cohort C - HER2-low 2L GC/GEJCdisitamab vedotindisitamab vedotin + tucatinib
Cohort C - HER2-low 2L GC/GEJCtucatinibdisitamab vedotin + tucatinib
Cohort A - HER2-low 2L or 3L breast cancerdisitamab vedotindisitamab vedotin + tucatinib
Cohort B - HER2+ 3L or higher breast cancerdisitamab vedotindisitamab vedotin + tucatinib
Cohort B monotherapy - HER2+ 3L or higher breast cancerdisitamab vedotindisitamab vedotin monotherapy
Primary Outcome Measures
NameTimeMethod
Number of participants with dose limiting toxicities DLTs) in dose escalation phaseUp to 28 days
Number of participants with adverse events (AEs)Through 30 days after the last study treatment; approximately 5 years

Any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention

Number of participants with laboratory abnormalitiesThrough 30-37 days after the last study treatment: approximately 5 years
Number of participants with dose alterationsThrough 30-37 days after the last study treatment: approximately 5 years
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessmentApproximately 3 years

The proportion of participants with confirmed response (CR) or partial response (PR) according to RECIST v1.1.

Secondary Outcome Measures
NameTimeMethod
Duration of response (DOR) per RECIST v1.1 by investigator assessmentApproximately 5 years

The time from start of the first documentation of objective tumor response of CR or PR (that is subsequently confirmed) to the first documentation of progressive disease (PD) per RECIST v1.1, or to death due to any cause

Disease control rate (DCR) per RECIST v1.1 by investigator assessmentApproximately 5 years

The proportion of participants with stable disease (SD) or confirmed CR or PR according to RECIST v1.1.

Progression free survival (PFS) per RECIST v1.1 by investigator assessmentApproximately 5 years

The time from randomization (or Cycle 1 Day 1 for participants in dose escalation phase) to the first documentation of disease progression per RECIST v1.1 or death due to any cause.

Overall survival (OS)Approximately 5 years

The time from randomization (or Cycle 1 Day 1 for participants in dose escalation phase) to the date of death due to any cause.

Pharmacokinetic (PK) parameter - Maximum concentration (Cmax)Through 30-37 days after the last study treatment; approximately 5 years
PK parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)Approximately 1 month
Incidence of anti-drug antibodies (ADAs) against disitamab vedotinThrough 30-37 days after the last study treatment; approximately 5 years

Trial Locations

Locations (39)

Azienda Ospedaliera Universitaria Integrata di Verona

🇮🇹

Verona, Other, Italy

Arizona Cancer Center / University of Arizona

🇺🇸

Tucson, Arizona, United States

Chao Family Comprehensive Cancer Center University of California Irvine

🇺🇸

Orange, California, United States

University of California, San Francisco | HDFCCC - Hematopoietic Malignancies

🇺🇸

San Francisco, California, United States

UCLA Department of Medicine - Hematology & Oncology

🇺🇸

Santa Monica, California, United States

Colorado West Healthcare, dba Grand Valley Oncology

🇺🇸

Grand Junction, Colorado, United States

Praxair Cancer Center / Danbury Hospital

🇺🇸

Danbury, Connecticut, United States

The Whittingham Cancer Center / Norwalk Hospital

🇺🇸

Norwalk, Connecticut, United States

MedStar Georgetown University Hospital

🇺🇸

Washington, District of Columbia, United States

Massachusetts General Hospital

🇺🇸

Boston, Massachusetts, United States

Dana Farber Cancer Institute

🇺🇸

Boston, Massachusetts, United States

Saint Luke's Cancer Institute LLC

🇺🇸

Kansas City, Missouri, United States

Washington University in St Louis

🇺🇸

Saint Louis, Missouri, United States

Renown Oncology

🇺🇸

Reno, Nevada, United States

San Juan Oncology Associates

🇺🇸

Farmington, New Mexico, United States

Memorial Sloan Kettering Cancer Center

🇺🇸

New York, New York, United States

Zangmeister Cancer Center

🇺🇸

Columbus, Ohio, United States

Saint Francis Hospital / Bon Secours - South Carolina

🇺🇸

Greenville, South Carolina, United States

SCRI Oncology Partners

🇺🇸

Nashville, Tennessee, United States

Carbone Cancer Center / University of Wisconsin

🇺🇸

Madison, Wisconsin, United States

Peninsula and South East Oncology

🇦🇺

Frankston, Other, Australia

BC Cancer Kelowna

🇨🇦

Kelowna, British Columbia, Canada

Ottawa Hospital Cancer Centre

🇨🇦

Ottawa, Ontario, Canada

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

University Health Network, Princess Margaret Hospital

🇨🇦

Toronto, Ontario, Canada

Istituto Europeo di Oncologia

🇮🇹

Milano, Other, Italy

Chungbuk National University Hospital

🇰🇷

Cheongju-si, Other, Korea, Republic of

Gachon University Gil Medical Center

🇰🇷

Incheon, Other, Korea, Republic of

Seoul National University Bundang Hospital

🇰🇷

Seongnam-si, Other, Korea, Republic of

Severance Hospital, Yonsei University Health System

🇰🇷

Seoul, Other, Korea, Republic of

St. Vincent's Hospital, The Catholic University of Korea

🇰🇷

Suwon-si, Other, Korea, Republic of

Samsung Medical Center

🇰🇷

Seoul, Korea, Republic of

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Other, Spain

L'Institut Catala d'Oncologia

🇪🇸

Barcelona, Other, Spain

START Madrid-CIOCC_Hospital HM Sanchinarro

🇪🇸

Madrid, Other, Spain

Hospital Clinico Universitario de Valencia

🇪🇸

Valencia, Other, Spain

St Bartholomew's Hospital

🇬🇧

London, Other, United Kingdom

The Royal Marsden NHS Foundation Trust (RM)

🇬🇧

London, Other, United Kingdom

Royal Marsden Hospital Sutton

🇬🇧

Surrey, Other, United Kingdom

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