This is a Phase II, multisite, open-label study consisting of two parts in participants with advanced/metastatic Non-small Cell Lung Cancer (NSCLC) which progressed after a first-line chemoimmunotherapy to evaluate the combination of pumitamig (also known as BNT327, BMS-986545 or PM8002) with standard of care.

Part 1 is a safety run-in with pumitamig (Dose 1 or Dose 2) plus docetaxel and will include up to 12 participants in total to be treated in Part 1A and 1B sequentially.

Part 2 is a dose expansion at the deemed safe dose of pumitamig plus docetaxel and will include up to 54 participants.

If the dose level (either from Part 1A or 1B) seems tolerable, an internal review committee will decide if the study can proceed to Part 2 and enroll additional participants.

In Part 2, participants who consent will be included in a separate cohort in which they will receive the same treatment as the other participants in Part 2, but in addition to a fresh baseline tumor biopsy, they will be required to provide an on-treatment tumor biopsy sample for additional analyses.

Study participants will receive pumitamig in combination with docetaxel until disease progression, the occurrence of intolerable toxicity, study participant withdrawal, death, study termination or 2-year limit (whichever comes first).

After completion of study treatment, except for participants who withdraw informed consent, a long-term follow-up will be conducted for all participants to record disease progression, subsequent new anticancer treatments, and survival status.

Key Inclusion Criteria:

• Have histologically or cytologically confirmed diagnosis of Stage IV NSCLC that has documented radiographic progression on one or after one prior line of systemic treatment (programmed death-1 [PD-1]/ programmed death ligand-1 [PD-L1] inhibitor and platinum-based chemotherapy concomitantly) in advanced/metastatic setting per the American Joint Committee on Cancer staging system, 9th edition.

  • Participants must have received minimum two cycles of immunotherapy in first-line treatment to be eligible to this study.
  • Only one prior line of immunotherapy containing regimen is allowed in an advanced/metastatic setting. If participant had received adjuvant immunotherapy the disease-free interval (after the last dose of adjuvant immunotherapy) should be at least 6 months.
  • Historical PD-L1 results must be available.
  • Participants with actionable genetic alterations may be enrolled if they received locally approved and available targeted agent in combination with immunotherapy in first-line advanced/metastatic setting.
  • Enrollment of participants with primary resistance (best response being radiological progression to prior immunochemotherapy) will be kept below 30% in the overall study population.

• Have at least one measurable lesion as the targeted lesion based on RECIST v1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been documented after irradiation. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.

• Participants must provide tumor tissue samples obtained ≤18 months prior to enrollment. For the additional cohort in Part 2, both baseline (freshly obtained) and on-treatment tumor biopsy samples are required.

• Eastern cooperative oncology group performance status of 0 or 1.

• Adequate organ function as defined in the protocol.

Key Exclusion Criteria:

• Have a known or suspected hypersensitivity to the study treatments, their metabolites or formulation of excipients including polysorbate 80 (see Docetaxel label).
• Participants who received prior treatment with anti-vascular endothelial growth factor (VEGF) monoclonal antibody, or anti-PD-(L)-1/aVEGF bispecific antibody or docetaxel as monotherapy or in combination with other agents.
• Have received more than one prior lines of therapies in advanced/metastatic setting.
• Have received systemic corticosteroids (at a dosage greater than 10 mg/day of prednisone or an equivalent dose of other corticosteroids) within 7 days prior to the initiation of study treatment (except for docetaxel premedication). Note: local, intranasal, intraocular, intra-articular or inhaled corticosteroids, short term use (≤7 days) of corticosteroids for prophylaxis (e.g., prevention of contrast agent allergy) or treatment of non autoimmune conditions (e.g., delayed hypersensitivity reactions caused by exposure to allergens) are allowed.
• Participants who have received prior radiotherapy may be enrolled if they have no acute toxicity related to this therapy.
• Have uncontrolled hypertension or poorly controlled diabetic conditions within 7 days prior to the first dose of study treatment.
• Have a serious or non-healing wound, or (incompletely healed) bone fracture. This includes history (within 6 months prior to study entry) or risk of abdominal fistula, tracheoesophageal fistula, gastrointestinal perforation, or intra abdominal abscess or esophageal and gastric varices, or acute gastrointestinal bleeding. In addition, the participant must have undergone correction (or spontaneous healing) of the perforation/fistula and/or the underlying process causing the fistula/perforation.
• Participants with significant risk of hemorrhage as defined in the protocol.
• Have superior vena cava syndrome or symptoms of spinal cord compression.

NOTE: Other protocol defined Inclusion/Exclusion criteria apply.