Study to Investigate Petosemtamab in Adults With Metastatic Non-Small Cell Lung Cancer

Inclusion Criteria:

* Able to provide written informed consent and is willing and able to comply with all study procedures and contraception requirements
* Age ≥ 18 years at the signing of ICF
* At least 1 measurable lesion as defined by RECIST 1.1
* ECOG performance status of 0 or 1
* Life expectancy ≥ 12 weeks, in the opinion of the Investigator
* Adequate hematologic function
* Creatinine clearance ≥ 60 mL/min calculated according to the Cockroft and Gault formula
* Adequate liver function
* Serum albumin ≥ 3 g/dL
* Serum magnesium and corrected calcium, Grade ≤ 1 alteration
* Participants of childbearing potential must agree to use highly effective contraception methods for the duration of study participation
* Histologically confirmed metastatic (Stage IV) sqNSCLC with PD-L1 TPS ≥ 50%
* No prior systemic treatment for metastatic disease
* Testing is required per local SOC and availability of testing to document absence of actionable genomic tumor aberrations
* Histologically confirmed metastatic (Stage IV) non-squamous NSCLC with PD-L1 TPS ≥ 50%

Exclusion Criteria:

* Has untreated CNS metastases and/or carcinomatous meningitis
* Participation in an interventional clinical study with any investigational drug within 4 weeks prior to the first dose of study treatment OR participation in any clinical study with petosemtamab at any time prior to the first dose of study treatment, regardless of whether petosemtamab was received
* Participants who received prior treatment with a PD-(L)1 inhibitor
* Participants who have received prior systemic chemotherapy, targeted or biological antineoplastic therapy for metastatic NSCLC
* Any systemic anticancer therapy within 4 weeks prior to the first dose of study treatment
* Major surgery or radiotherapy within 3 weeks prior to the first dose of study treatment. Participants who received prior radiotherapy to ≥ 25% of bone marrow are not eligible, regardless of when it was received.
* Persistent Grade \> 1 clinically significant toxicities related to prior antineoplastic therapies using NCI-CTCAE v5.0
* History of hypersensitivity reaction to any of the excipients of petosemtamab or pembrolizumab
* Unstable angina; history of congestive heart failure of Class II-IV New York Heart Association criteria or serious cardiac arrhythmia requiring treatment (except atrial fibrillation, paroxysmal supraventricular tachycardia); or history of myocardial infarction within 6 months prior to the first dose of study treatment
* History of prior malignancies within the last 5 years, with the exception of excised local cancer
* Current dyspnea at rest of any origin or other diseases requiring continuous oxygen therapy, including participants with a history of ILD (eg, pneumonitis or pulmonary fibrosis) or evidence of ILD on baseline chest CT scan
* Current serious illness or medical condition, including but not limited to uncontrolled active infection and clinically significant pulmonary, metabolic, or psychiatric disorders
* Known infectious disease
* Participants who are pregnant or breastfeeding.