A study of sigvotatug vedotin versus docetaxel in previously treated non-small cell lung cancer (Be6A Lung-01)

Prior treatment

• Prior therapy: • Prior treatment with antimicrotubule agents (taxanes, vinca alkaloids, or MMAEs) in the locally advanced, unresectable/refractory, or metastatic setting. - Prior antimicrotubule agent exposure in curative settings (including adjuvant, neoadjuvant, or chemoradiotherapy) is permissible. • Received more than 1 prior line of cytotoxic chemotherapy in the locally advanced, unresectable/refractory, or metastatic setting. - Prior cytotoxic chemotherapy in curative settings is permissible. • At least 14 days must have elapsed from the last dose of radiotherapy until Cycle 1 Day 1. Participants must have recovered from all radiation related toxicities that would otherwise prevent trial participation. Palliative radiotherapy within the 14 days prior to Cycle 1 Day 1 may be allowed upon discussion with the sponsor’s medical monitor or their designee. • Prior radiation therapy to the lung parenchyma that is >30 Gray (Gy) within 6 months of Cycle 1 Day 1. • Any systemic anticancer therapy (standard or experimental) within 21 days prior to Cycle 1 Day 1. • Participants with Grade ≥2 ongoing toxicities associated with prior therapies will be excluded, with the exception of alopecia.

Lab values

• Uncontrolled diabetes mellitus, defined as HbA1c ≥8.0% or HbA1c between 7% and <8.0% with associated diabetes symptoms (polyuria or polydipsia) that are not otherwise explained.
• Participants with any of the following respiratory conditions: • Evidence of noninfectious ILD or pneumonitis that: o Was previously diagnosed and required systemic steroids, or o Is currently diagnosed and managed, or o Is suspected on radiologic imaging at screening • Known DLCO (adjusted for hemoglobin) <50% predicted • Any Grade ≥3 pulmonary disease unrelated to underlying malignancy including, but not limited to: o Pulmonary emboli within 3 months of Cycle 1 Day 1 o Severe asthma requiring systemic corticosteroids within 30 days prior to Cycle 1 Day 1 or is not well controlled with low-dose inhaled corticosteroids/long-acting beta-2 agonists o Severe chronic obstructive pulmonary disease requiring supplemental oxygen or systemic corticosteroids o Any autoimmune or inflammatory disorders with significant pulmonary parenchymal involvement at time of screening (ie, rheumatoid arthritis, Sjögren's syndrome, sarcoidosis, etc)

Other

• Pre-existing peripheral neuropathy Grade ≥2 per NCI CTCAE v5.0.

• Histologically or cytologically confirmed diagnosis of locally advanced, unresectable (Stage IIIB, IIIC), or metastatic (Stage IV: M1a, M1b, or M1c) NSCLC per the American Joint Committee on Cancer (AJCC) Staging Manual, Version 8.0, and the Union for International Cancer Control (UICC) Staging System (Eighth edition).
• Participants must have NSCLC with nonsquamous histology: oTumors with squamous, or predominantly squamous histology are excluded. oTumors with small cell elements are excluded
• Participants must have received the following prior therapies and progressed during or relapsed after receiving their most recent prior therapy: • Participants with no known AGAs must fulfill 1 of the following conditions: o Received a platinum based combination therapy for the treatment of metastatic or recurrent disease and a PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy), unless contraindicated. o Experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting and received a PD-(L)1 monoclonal antibody at any time during the course of treatment. • Participants with known AGAs (eg, EGFR mutations, ALK translocations, or other relevant actionable mutations) must fulfill the following conditions: o Must have received at least 1 relevant AGA-targeted therapy and, in the opinion of the investigator, additional AGA-targeted therapy is not in the best interest of the participant. o Received a platinum-based combination therapy for the treatment of metastatic or recurrent disease, or experienced disease progression within 6 months of the last dose of platinum-based chemotherapy in the adjuvant, neoadjuvant, or chemoradiotherapy setting. o May have received up to 1 PD-(L)1 monoclonal antibody (concurrently or sequentially with platinum-based chemotherapy).
• Measurable disease based on RECIST v1.1, as determined by investigator.