Clinical Trials List
Protocol NumberC5731004/SGNDV-004
NCT Number(ClinicalTrials.gov Identfier)NCT06157892
Active
2024-04-01 - 2030-01-31
Phase I/II
Recruiting4
ICD-10C79.00
Secondary malignant neoplasm of unspecified kidney and renal pelvis
ICD-10C79.01
Secondary malignant neoplasm of right kidney and renal pelvis
ICD-10C79.02
Secondary malignant neoplasm of left kidney and renal pelvis
ICD-10Z51.12
Encounter for antineoplastic immunotherapy
ICD-9198.0
Secondary malignant neoplasm of kidney
A Phase 1b/2 Open-Label Study of Disitamab Vedotin in Combination With Other Anticancer Therapies in Solid Tumors
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Trial Applicant
Pharmaceutical Research Associates Taiwan Inc.
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Sponsor
-
Trial scale
Multi-Regional Multi-Center
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Update
2026/02/01
Investigators and Locations
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- Yung-Chang Lin 無
- 黃文冠 無
- Hung-Chih Hsu 無
- Chan-Keng Yang 無
- 陳安欣 無
- Wen-Chi Shen 無
- Jen-Shi Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Co-Principal Investigator
- 徐偉勛 無
- YEN-SHEN LU 無
- 張端瑩 無
- Kun-Huei Yeh Division of Hematology & Oncology
- 吳宗哲 無
- Wei-Wu Chen 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Principal Investigator
Chia-Jui Yen
Co-Principal Investigator
- 鍾秉軒 無
- 顏志傑 無
- 劉奕廷 無
- Shang-Yin Wu 無
The Actual Total Number of Participants Enrolled
0 Recruiting
Condition/Disease
Breast Neoplasms 、Gastroesophageal Junction Adenocarcinoma
Objectives
Main purpose:
● Identify the maximum tolerated dose (MTD) and/or optimal dose when disitamab vedotin and tucatinib are administered together.
● Investigate the safety and tolerability of disitamab vedotin plus tucatinib in the following scenarios:
◦ Low HER2 second-line (2L) or third-line (3L) advanced BC
◦ HER2+ 3L+ advanced BC
◦ Low HER2 2L advanced GC/GEJC
◦ HER2+ 2L or 3L advanced GC/GEJC
● Evaluate the antitumor activity of disitamab vedotin plus tucatinib in the following scenarios:
◦ Low HER2 2L or 3L advanced BC
◦ HER2+ 3L+ advanced BC
◦ Low HER2 2L advanced GC/GEJC
◦ HER2+ 2L or 3L advanced GC/GEJC (Secondary)
● Evaluate the antitumor activity of disitamab vedotin plus tucatinib
● Investigate the safety and tolerability of disitamab vedotin plus tucatinib Pharmacokinetics (PK) of tucatinib, intact antibody, and unconjugated monomethyl auristatin E (MMAE)
●Investigating the immunogenicity of disitamab vedotin
Test Drug
Dry powder injection
Film-coated tablets
Film-coated tablets
Active Ingredient
Disitamab Vedotin
Tucatinib
Tucatinib
Dosage Form
240
116
116
Dosage
45mg/Vial
50mg
50mg
Endpoints
● Incidence of dose-limiting toxicities (DLTs) during dose escalation
● Types, incidence, severity, and relevance of adverse events (AEs)
● Types, incidence, and severity of abnormal laboratory test results, and significant changes compared to baseline
● Frequency of treatment interruption, dose reduction, and discontinuation due to AEs
● ORR (confirmed complete response [CR] and confirmed partial response [PR]) assessed by the trial principal investigator according to RECIST v1.1 (Treatment Response Assessment Criteria for Solid Tumors Version 1.1).
● Types, incidence, severity, and relevance of adverse events (AEs)
● Types, incidence, and severity of abnormal laboratory test results, and significant changes compared to baseline
● Frequency of treatment interruption, dose reduction, and discontinuation due to AEs
● ORR (confirmed complete response [CR] and confirmed partial response [PR]) assessed by the trial principal investigator according to RECIST v1.1 (Treatment Response Assessment Criteria for Solid Tumors Version 1.1).
Inclution Criteria
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 and Optimization Phase Inclusion Criteria
Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
Locally-advanced, unresectable, or metastatic stage
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 intolerance to endocrine therapy or 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.
Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated.
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 for advanced disease.
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
Cohort D (HER2+ LA/mGC/GEJC) Inclusion Criteria
Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
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 plus fluoropyrimidine and platinum containing chemotherapy if no contraindication.
Prior T-DXd treatment is allowed
Prior PD1 inhibitor therapy is allowed
No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC
General Inclusion Criteria
Measurable disease according to RECIST v1.1
Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1
Dose Escalation and Optimization Phase Inclusion Criteria
Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
Locally-advanced, unresectable, or metastatic stage
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 intolerance to endocrine therapy or 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.
Participants with HR negative, HER2-low and PD-L1-positive (CPS 10 or greater) tumors must have received pembrolizumab (or other PD-(L)1 inhibitor) with chemotherapy if available as local standard of care therapy and not medically contraindicated.
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 for advanced disease.
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
Cohort D (HER2+ LA/mGC/GEJC) Inclusion Criteria
Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
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 plus fluoropyrimidine and platinum containing chemotherapy if no contraindication.
Prior T-DXd treatment is allowed
Prior PD1 inhibitor therapy is allowed
No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC
Exclusion Criteria
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
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
The Estimated Number of Participants
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Taiwan
12 participants
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Global
178 participants
