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.

Participants in this study must have breast cancer or gastric cancer. Participants must
have tumors that have HER2 on them. This allows the cancer to grow more quickly or spread
faster. There are few treatment options for patients with advanced or metastatic solid
tumors that express HER2.

This clinical trial uses an experimental drug called disitamab vedotin (DV). Disitamab
vedotin is a type of antibody drug conjugate or ADC. ADCs are designed to stick to cancer
cells and kill them.

This clinical trial uses a drug called tucatinib, which has been approved to treat cancer
in the United States and some other countries. This drug is sold under the brand name
TUKYSA®.

This study will test how safe and how well DV with tucatinib works for participants with
solid tumors. This study will also test what side effects happen when participants take
these drugs. A side effect is anything a drug does to the body besides treating the
disease.

Objectives

This clinical trial is to evaluate disitamab vedotin 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 will
be assessed in the optimization phase for both safety and efficacy in HER2-expressing
LA/mBC and LA/mGC/GEJC. Once the safety and efficacy profile of disitamab vedotin plus
tucatinib has been established and a disitamab vedotin dose with the optimum benefit/risk
ratio has been determined the disitamab vedotin plus tucatinib combination therapy will
be evaluated in an expansion phase with 4 expansion cohorts in subjects with HER2-low
LA/mGC/GEJC, HER2+ LA/mGC/GEJC, HER2-low LA/mBC, and HER2+ LA/mBC.

Eligibility

1. Measurable disease according to RECIST v1.1
2. Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or 1 Dose Escalation and Optimization Phase Inclusion Criteria
3. Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma or breast carcinoma
4. Locally-advanced, unresectable, or metastatic stage
5. 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
6. Histologically or cytologically confirmed diagnosis of breast carcinoma
7. Locally-advanced, unresectable, or metastatic stage
8. HER2-low status determined by most recent local assessment (IHC 1+ or IHC 2+/ISH-negative)
9. Prior therapies requirements
10. No more than 3 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mBC.
11. Participants with known BRCA mutation must have received a PARP-inhibitor where available and not medically contraindicated
12. 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
13. Participants with HR+ tumors must have intolerance to endocrine therapy or endocrine therapy refractory disease:
14. Progressed on =2 lines of endocrine therapy for LA/mBC AND had received a CDK4/6 inhibitor in the adjuvant or metastatic setting OR
15. 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
16. 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.
17. 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
18. Histologically or cytologically confirmed diagnosis breast carcinoma
19. Locally-advanced, unresectable, or metastatic stage
20. HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
21. Participants must have:
22. Received prior trastuzumab, pertuzumab and a taxane if available as local standard of care therapy for advanced disease.
23. Have progression on or after, or intolerant to, T-DXd or other topoisomerase I inhibitor therapies
24. 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
25. Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
26. Locally-advanced, unresectable, or metastatic stage
27. HER2-low expression defined as IHC 1+ or IHC 2+/ISH-negative determined by most recent local assessment
28. Willing and able to provide archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumor tissue blocks
29. Participants must have received:
30. Prior systemic therapy with platinum, fluorouracil, or taxane for locally advanced unresectable or metastatic disease
31. Progression within 6 months of last dose of (neo)adjuvant cytotoxic chemotherapy is considered as 1 line of systemic therapy for LA/mGC/GEJC
32. Prior anti-PD-(L)1 therapy is allowed
33. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADC) for LA/mGC/GEJC
34. Must not have received prior treatment with HER2 directed therapy Cohort D (HER2+ LA/mGC/GEJC) Inclusion Criteria
35. Histologically or cytologically confirmed diagnosis of gastric or gastroesophageal junction adenocarcinoma
36. Locally-advanced, unresectable, or metastatic stage
37. HER2+ status determined by most recent local assessment (IHC 3+ or IHC 2+/ISH+)
38. Participants must have:
39. Received prior trastuzumab plus fluoropyrimidine and platinum containing chemotherapy if no contraindication.
40. Prior T-DXd treatment is allowed
41. Prior PD1 inhibitor therapy is allowed
42. No more than 2 prior systemic cytotoxic chemotherapy regimens (including ADCs) for LA/mGC/GEJC

Treatment Sites in Georgia