A Study of Ladiratuzumab Vedotin in Advanced Solid Tumors

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

This trial will study ladiratuzumab vedotin (LV) alone and with pembrolizumab to find out if it works to treat different types of solid tumors. It will also find out what side effects may occur. A side effect is anything the drug does besides treating cancer.

This trial is designed to assess the antitumor activity, safety, and tolerability of LV alone and with pembrolizumab, for the treatment of solid tumors. Participants with the following advanced solid tumors will be enrolled:

Cohort 1: small cell lung cancer (SCLC) Cohort 2: non-small cell lung cancer-squamous (NSCLC-squamous) Cohort 3: non-small cell lung cancer-nonsquamous (NSCLC-nonsquamous) Cohort 4: head and neck squamous cell carcinoma (HNSCC) Cohort 5: esophageal squamous cell carcinoma (esophageal-squamous) Cohort 6: gastric and gastroesophageal junction (GEJ) adenocarcinoma Cohort 7: castration-resistant prostate cancer (CRPC) Cohort 8: melanoma

Participants will continue to receive study treatment until disease progression, unacceptable toxicity, investigator decision, consent withdrawal, study termination by the sponsor, pregnancy, or death, whichever comes first.

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.