A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

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.