This trial is designed to assess the antitumor activity, safety, and tolerability of LV 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
- 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.
