Open-Label Phase 2 Study of Ladiratuzumab Vedotin (LV) for Unresectable Locally Advanced or Metastatic Solid Tumors

Condition: Small Cell Lung Cancer, Non-small Cell Lung Cancer, Squamous, Non-small Cell Lung Cancer, Non-squamous, Head and Neck Squamous Cell Carcinoma, Esophageal Squamous Cell Carcinoma, Gastric Adenocarcinoma, Gastroesophageal Junction Adenocarcinoma, Prostate Cancer, Melanoma

Study Type: Interventional

Clinical Trials Identifier NCT 8-digits: NCT04032704

Sponsor: Seagen Inc.

Phase: Phase 2

Eligibility:

• Age: minimum 18 Years maximum N/A
• Gender: All

Inclusion Criteria:

• All Cohorts
• Measurable disease according to RECIST v1.1 as assessed by the investigator
• Eastern Cooperative Oncology Group (ECOG) Performance Score of 0 or 1
• Cohort 1: SCLC
• Must have extensive stage disease
• Must have disease progression during or following prior platinum-based systemic chemotherapy for extensive stage disease;
• No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
• No more than 1 prior line of cytotoxic chemotherapy for extensive disease stage
• May have received prior anti-PD(L)1 therapy
• Cohort 2: NSCLC-squamous
• Must have unresectable locally advanced or metastatic disease
• Must have disease progression during or following systemic therapy
• Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
• Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced stage disease.
• Participants with known epidermal growth factor receptor (EGFR), anaplastic lymphoma kinase (ALK), reactive oxygen species (ROS), BRAF, or other actionable mutations are not eligible
• No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
• Must have received prior anti-PD(L)1 therapy, unless contraindicated
• Cohort 3: NSCLC-nonsquamous
• Must have unresectable locally advanced or metastatic disease
• Must have disease progression during or following systemic therapy
• Participants must have progressed during or after a platinum-based combination therapy administered for the treatment of metastatic disease, OR
• Participants must have progressed within 6 months of last dose of platinum-based adjuvant, neoadjuvant, or definitive chemotherapy, or concomitant chemoradiation regimen for early stage or locally advanced state disease.
• Participants with known EGFR, ALK, ROS, BRAF, tropomyosin receptor kinase (TRK), or other actionable mutations are not eligible
• Must have had prior platinum-based chemotherapy
• No more than 1 prior line of cytotoxic chemotherapy for their advanced disease
• Must have received prior anti-PD(L)1 therapy, unless contraindicated
• Cohort 4: HNSCC
• Must have unresectable locally recurrent or metastatic disease
• Must have disease progression during or following prior line of systemic therapy
• Disease progression after treatment with a platinum-containing regimen for recurrent/metastatic disease; or
• Recurrence/progression within 6 months of last dose of platinum therapy given as part of a multimodal therapy in the curative setting
• No more than 1 line of cytotoxic chemotherapy for their advanced disease
• May have received prior anti-PD(L)1 therapy, unless contraindicated
• Cohort 5: esophageal-squamous
• Must have unresectable locally advanced or metastatic disease
• Must have disease progression during or following systemic therapy
• Must have had prior platinum-based chemotherapy
• No more than 1 line of cytotoxic chemotherapy for their advanced disease
• Cohort 6: gastric and GEJ adenocarcinoma
• Must have unresectable locally advanced or metastatic disease
• Must have received prior platinum-based therapy
• Must have disease progression during or following systemic therapy
• Participants with known human epidermal growth factor receptor 2 (HER2) overexpression must have received prior HER2-targeted therapy
• No more than 1 line of prior cytotoxic chemotherapy for their advanced disease
• Participants may have received prior anti-PD(L)1 therapy, unless contraindicated
• Cohort 7: CRPC
• Must have histologically or cytologically confirmed adenocarcinoma of the prostate
• Participants with components of small cell of neuroendocrine histology are excluded
• Must have metastatic castration-resistant disease
• Must have been ≥28 days between cessation of androgen receptor-targeted therapy and start of study treatment
• Must have received no more than 1 prior line of androgen receptor-targeted therapy for metastatic castration-sensitive prostate cancer or CRPC
• No prior cytotoxic chemotherapy in the metastatic CRPC setting
• For participants who received cytotoxic chemotherapy in CSPC, at least 6 months must have elapsed between last dose of chemotherapy and start of study treatment
• No more than 1 prior line of cytotoxic chemotherapy for CSPC
• Participants with measurable and non-measurable disease are eligible if the following criteria are met:
• A minimum starting PSA level ≥1.0 ng/mL
• Participants with measurable soft tissue disease must have evidence of measurable soft tissue disease according to PCWG3 criteria.
• Participants with non-measurable disease must have documented rising PSA levels or appearance of new lesion according to PCWG3
• Participants with known breast cancer gene (BRCA) mutations are excluded
• No prior radioscope therapy or radiotherapy to ≥30% of bone marrow
• Cohort 8: Melanoma
• Must have histologically or cytotoxically confirmed cutaneous malignant melanoma
• Participants with mucosal, acral, or uveal melanoma are excluded
• Must have locally advanced unresectable or metastatic stage disease
• Must have measurable disease
• Must have progressive disease following anti-PD(L)1 therapy

Exclusion Criteria:

• Active concurrent malignancy or a previous malignancy within the past 3 years
• Any anticancer therapy within 3 weeks of starting study treatment. Participants who are/were on adjuvant hormonal therapy for the treatment of malignancies with negligible risk of metastases are eligible.
• Known active central nervous system lesions
• Active viral, bacterial, or fungal infection requiring systemic treatment within 7 days prior to the first dose of LV
• Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
• Ongoing sensory or motor neuropathy of Grade ≥2
• Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with congestive heart failure
• Has received prior radiotherapy within 2 weeks of start of study treatment
• Has received a live vaccine within 30 days of the planned start of study therapy.

View trial on ClinicalTrials.gov