A Study of Disitamab Vedotin Alone or with Other Anticancer Drugs in Solid Tumors
- Conditions
- A/mGC/GEJC (locally advanced unresectable or metastatic gastric cancer and gastroesophageal junction adenocarcinoma, collectively) and LA/mBC (locally advanced metastatic breast cancer)MedDRA version: 21.0Level: PTClassification code: 10030137Term: Oesophageal adenocarcinoma Class: 100000004864MedDRA version: 23.0Level: PTClassification code: 10083232Term: HER2 negative breast cancer Class: 100000004864MedDRA version: 21.1Level: PTClassification code: 10017758Term: Gastric cancer Class: 100000004864MedDRA version: 23.0Level: PTClassification code: 10065430Term: HER2 positive breast cancer Class: 100000004864Therapeutic area: Diseases [C] - Neoplasms [C04]
- Registration Number
- CTIS2023-507555-29-00
- Lead Sponsor
- Seagen Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 371
Age =18 years, or considered an adult by local regulations, at time of consent, For Subjects in the Dose Escalation Phase: Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma, For Subjects in the Dose Escalation Phase: Locally-advanced, unresectable, or metastatic stage, For Subjects in the Dose Escalation Phase: HER2 status IHC 1+ or higher by most recent local assessment., For Subjects in the Dose Escalation Phase: All subjects must have experienced disease progression on or after standard of care therapies or be intolerant of standard of care therapies. a.BC subjects: Must meet eligibility criteria in Sections 5.1.3 or 5.1.4 depending on HER2 status b.GC/GEJC subjects: Must meet eligibility criteria in Section 5.1.5, For Subjects in Cohort A (HER2-Low Breast Cancer): Histologically or cytologically confirmed diagnosis of breast carcinoma, For Subjects in Cohort A (HER2-Low Breast Cancer): Locally-advanced, unresectable, or metastatic stage, For Subjects in Cohort A (HER2-Low Breast Cancer): HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH negative) based on ASCO and College of American Pathologists (CAP) guidelines for assessment of HER2 in BC for interpretation of HER2 expression and amplification (Wolff 2018b), For Subjects in Cohort A (HER2-Low Breast Cancer): Prior therapies requirements: a.No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC. Subjects previously treated with (neo)adjuvant cytotoxic chemotherapy and have disease relapsed within 6 month of treatment is considered to have received 1 line of cytotoxic therapy for LA/mBC. b.Subjects with known BRCA mutation must have received a PARP-inhibitor, where available and not medically contraindicated c.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 d.Subjects with HR+ tumors must have endocrine therapy refractory disease: i.Progressed on =2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR ii.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 e.Subjects with HR+ HER2-low tumors must have progression on or after, or be intolerant to, prior chemotherapy. f. Subjects 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., For Subjects in Cohort B (HER2+ Breast Cancer): Histologically or cytologically confirmed diagnosis breast carcinoma, For Subjects in Cohort B (HER2+ Breast Cancer): Locally-advanced, unresectable, or metastatic stage, The subject or the subject’s legally authorized representative must provide documented informed consent, For Subjects in Cohort B (HER2+ Breast Cancer): HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+) according to ASCO and CAP guidelines for assessment of HER2 in BC (Wolff 2018b), For Subjects in Cohort B (HER2+ Breast Cancer): All subjects must have: a.Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy. b.Have progression on or after, or intoler
Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin or tucatinib, Subjects who have received major surgery within 4 weeks prior to Cycle 1 Day 1 (dose escalation phase) or randomization in the optimization or expansion phases must have recovered adequately., Subjects requiring chronic oxygen therapy or have = Grade 3 dyspnea, hypoxia, or other pulmonary disease unrelated to underlying malignancy., Subjects who have received a live or live-attenuated vaccine within 30 days prior to Cycle 1 Day 1 (dose escalation phase) or randomization in the optimization or expansion phases. Administration of killed vaccines is allowed., Subjects who have received whole blood or plasma transfusions within 14 days prior to the Cycle 1 Day 1 (dose escalation phase) or randomization in the optimization or expansion phases., Subjects who are pregnant, breastfeeding, or planning a pregnancy., Current therapy with other investigational agents., Other serious underlying medical condition that, in the opinion of the investigator, would impair the subject’s ability to receive or tolerate the planned treatment and follow up., Unable to swallow oral tablets or capsules or any significant GI disease which would preclude the adequate oral absorption of medications., Have used a strong cytochrome P450 (CYP)2C8 inhibitor within 5 half lives of the inhibitor or have used a strong CYP2C8 or CYP3A4 inducer within 5 days prior to first dose of study treatment., Bowel obstruction, history or presence of inflammatory enteropathy or extensive intestinal resection (hemicolectomy or extensive small intestine resection with chronic diarrhea) or moderate to severe chronic diarrhea or any conditions that may alter oral drug absorption., Prior therapy with ADCs with MMAE payload, Presence of known chronic liver disease., Has ongoing = Grade 2 diarrhea of any etiology at screening., Pleural effusion or ascites with symptoms or requiring symptomatic treatment., Any other disease, metabolic disorder, or abnormal finding upon physical examination or laboratory examination that makes the subject unsuitable for receiving the investigational drug(s), affects the interpretation of study outcomes, or poses risks to subject safety, as determined by the investigator., Prior therapy with tucatinib, CNS and/or leptomeningeal metastasis. a.Subjects with treated CNS metastases (treatment modality includes whole brain radiation therapy, surgery, or radiosurgery, etc) are permitted if all of the following are met: i.CNS metastases have been clinically stable for at least 4 weeks without evidence of new or worsening CNS metastasis. ii.Subject is on a stable or decreasing dose of =10 mg/day of prednisone or equivalent. iii.Subject does not have leptomeningeal metastasis., Subjects who have received prior systemic anticancer treatment including investigational agents within 4 weeks (please consult medical monitor for permitting shorter interval for kinase inhibitors or other short half life anticancer drugs) prior to first dose of study treatment. a.Participants must have recovered from all AEs due to previous therapies to = Grade 1 or baseline (except for alopecia). Participants with = Grade 1 neuropathy may be eligible. b.If the participant had major surgery, the participant must have recovered adequately from the procedure and/or any complications from the surgery prior to starting study intervention., Subjects with acute, chronic, or symptoma
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method