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.