SGNDV-005 is a multi-cohort, multicenter, international, open-label Phase 2 study designed to assess the activity, safety, and tolerability of disitamab vedotin monotherapy for the treatment of subjects with previously treated, locally advanced or metastatic (LA/m) solid tumors with HER2 expression defined by IHC level 1+, 2+, and 3+.
Subjects will be enrolled into separate cohorts based on tumor type. There are 4 tumor specific cohorts: HNSCC (Cohort 1), NSCLC (Cohort 2), ovarian cancer (Cohort 3), and endometrial cancer (Cohort 4), with approximately 40 subjects in each cohort. Cohorts 1 through 4 will enroll up to approximately 30 subjects in each cohort whose disease displays HER2 expression of IHC ≥1+.
In general, subjects must have progressed during or after ≥1 prior line of systemic therapy for LA/m disease and must have progressed during or after, or be intolerant of, the most recent line of systemic therapy. Subjects must have measurable disease, ECOG performance status 0 to 1, and adequate baseline hepatic, renal, and hematologic function. Subjects must not have received prior HER2-directed ADC therapy, or have clinically significant cardiopulmonary disease, chronic liver disease, or uncontrolled central nervous system (CNS) metastases.
Study treatment is composed of disitamab vedotin Q2W until disease progression or unacceptable toxicity, pregnancy, death, withdrawal of consent, or termination of the study by the sponsor.
Arms and Interventions
Cohort 1
(HNSCC)
Population and HER2 Status:
Previously treated LA/m; HER2 IHC ≥1+
Open label study treatment, IV every 2 weeks:
Disitamab vedotin (monotherapy)
Cohort 2
(NSCLC)
Population and HER2 Status :
Previously treated LA/m; HER2 IHC ≥1+
Open label study treatment, IV every 2 weeks:
Disitamab vedotin (monotherapy)
Cohort 3
(Ovarian Cancer)
Population and HER2 Status:
Previously treated LA/m; HER2 IHC ≥1+
Open label study treatment, IV every 2 weeks:
Disitamab vedotin (monotherapy)
Cohort 4
(Endometrial Cancer)
Population and HER2 Status:
Previously treated LA/m; HER2 IHC ≥1+
Open label study treatment, IV every 2 weeks:
Disitamab vedotin (monotherapy)
Inclusion criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
- HER2 expression of 1+, 2+, or 3+, as determined by local IHC testing on a fresh or archival tumor tissue. Note: Participants with HER2 mutations are eligible.
- Measurable disease per RECIST v1.1 criteria as assessed by the investigator
- Able to provide formalin-fixed, paraffin-embedded (FFPE) tumor tissue blocks (or freshly sectioned slides)
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
Cohort 1:
- Pathologically-documented squamous cell carcinoma of the head and neck with primary tumor site arising from the oral cavity, oropharynx, hypopharynx, and larynx
- Unresectable locally recurrent or metastatic stage disease
- At least one measureable lesion by investigator assessment based on RECIST version 1.1
- Prior therapies:
- Participants must have disease progression after treatment with a platinum-based therapy
- No more than 1 line of cytotoxic chemotherapy for advanced disease
Cohort 2:
- Pathologically documented NSCLC
- Unresectable locally-advanced or metastatic stage disease
- Prior therapies
- Must have progressed during or after a platinum-based therapy or, within 6 months of platinum-based adjuvant, neoadjuvant, or concomitant chemoradiotherapy for early or locally-advanced stage disease
- Must have received prior anti-PD(L)1 therapy, unless contraindicated
- No more than 2 prior lines of cytotoxic chemotherapy for advanced disease
Cohort 3:
- Pathologically documented epithelial cancers of ovarian, fallopian tube, or peritoneal origin
- Unresectable locally-advanced or metastatic stage disease
- Prior therapies
- Must have platinum resistant disease (6 months or less between the completion of platinum-based treatment and identification of recurrence)
- Must not have received more than 4 lines of prior cytotoxic chemotherapies for advanced disease
- May have received prior anti-PD(L)1 therapy
Cohort 4:
- Must have pathologically documented adenocarcinoma of the endometrium
- Must have unresectable locally-advanced or metastatic stage disease.
- Prior therapies
- Must have relapsed/progressed after at least one prior platinum-based chemotherapy for recurrent, metastatic or primary unresectable disease
- Must not have received more than 3 lines of prior cytotoxic chemotherapies for advanced disease
- May have received prior anti-PD(L)1 therapy
Exclusion Criteria
This is not a complete list of inclusion and exclusion criteria. Please connect with a Principal Investigator for further information.
- Prior treatment with an MMAE-containing agent.
- Known hypersensitivity to any excipient contained in the drug formulation of disitamab vedotin.
- History of another invasive malignancy within 2 years before the first dose of study intervention, or any evidence of residual disease from a previously diagnosed malignancy.
- Active untreated CNS or leptomeningeal metastasis
Primary outcomes
- Confirmed Objective Response Rate (ORR) per Response Evaluation in Solid Tumors version 1.1 (RECIST v1.1) by investigator assessment
Secondary outcomes
- Number of participants with adverse events (AEs)
- Number of participants with laboratories abnormalities
- Number of participants with dose alterations due to AEs
- Confirmed Disease Control Rate (DCR) per RECIST v1.1 by investigator assessment
- Duration of Response (DOR) per RECIST v1.1 by investigator assessment
- Progression free survival (PFS) per RECIST v1.1 by investigator assessment
- Overall Survival (OS)
- Pharmacokinetic (PK) parameter - Area under the concentration-time curve to the time of the last quantifiable concentration (AUClast)
- PK parameter - Maximum concentration (Cmax)
- PK parameter - Trough concentration (Ctrough)
- Incidence of antidrug antibodies (ADAs)
Protocol Amendment 01, DV-005 HCP Page, 14Aug24