A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

This is an interventional treatment trial for Small Cell Lung Cancer focused on measuring SCLC, NSCLC-squamous, NSCLC-nonsquamous, HNSCC, GEJ adenocarcinoma, Seattle Genetics Read More

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 (Parts A and B)

  • 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
  • May have received prior anti-PD(L)1 therapy

• Cohort 2: NSCLC-squamous (Parts A and B)

  • 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 (Parts A and B)

  • 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 (Parts A and B)

  • 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 (Parts A and B)

  • 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 (Parts A and B)

  • 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 (Part B only)

  • 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 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 known breast cancer gene (BRCA) mutations are excluded
  • No prior radioisotope therapy or radiotherapy to ≥30% of bone marrow

• Cohort 8: Melanoma (Parts B and C)

  • Must have histologically or cytologically confirmed cutaneous malignant melanoma

    • Participants with mucosal, acral, or uveal melanoma are excluded
  • Must have locally advanced unresectable or metastatic stage disease
  • Must have progressive disease following anti-PD(L)1 therapy
  • Must have received BRAF +/- MEK inhibitor therapy if BRAF mutated (Part C)

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
• Any ongoing clinically significant toxicity associated with prior treatment (Grade 2 or higher)
• Ongoing sensory or motor neuropathy of Grade ≥2
• Has received prior radiotherapy within 2 weeks of start of study treatment
• History of interstitial lung disease.