• Participants must have histologically confirmed pancreatic cancer (adenocarcinoma, squamous, or adenosquamous histologies) that is metastatic and for which standard curative or palliative measures do not exist or are no longer effective. Locally advanced patients are not eligible.

• Participants must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as ≥20 mm (≥2 cm) by chest x-ray or as ≥10 mm (≥1 cm) with CT scan, MRI, or calipers by clinical exam.

• Participants must have received 8-12 cycles (4-6 months) of first-line FOLFIRINOX or modified FOLFIRINOX with stable disease or better.

• Age ≥18 years. Because no dosing or adverse event data are currently available on the use of domvanalimab + zimberelimab + APX005M in participants \<18 years of age, children are excluded from this study.

• ECOG performance status ≤1

• Participants must have adequate organ and marrow function as defined below:

‣ leukocytes ≥3,000/mcL

⁃ absolute neutrophil count ≥1,500/mcL

⁃ platelets ≥100,000/mcL

⁃ total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN), except in patients with documented Gilbert's syndrome, who must have a total bilirubin ≤ 3 x ULN

⁃ AST(SGOT)/ALT(SGPT) ≤ 2.5 x institution's upper limit of normal (ULN) for patients with no concurrent liver metastases, OR ≤ 5.0 x institution's ULN for patients with concurrent liver metastases creatinine OR glomerular filtration rate (GFR) creatinine ≤ 2 x ULN OR GFR measured by calculated creatinine clearance (CrCl) \> 45 mL/min. CrCl can be calculated using the Cockroft-Gault method.

⁃ Hemoglobin (Hgb) \>9.0 g/dL

• Participants with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression. If a participant has brain or meningeal metastases, the participant must meet the following criteria:

‣ Have no evidence of progression by neurologic symptoms or sign for at least 4 weeks prior to the first dose.

⁃ Metastatic brain lesions do not require immediate intervention.

⁃ Carcinomatous meningitis is excluded regardless of clinical stability.

• Participants with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, participants should be class 2B or better.

• Participants must be willing to undergo a pre-treatment fresh tumor biopsy.

• Participants must be willing to undergo an on-treatment tumor biopsy (if medically feasible).

• Participants must have archival tissue available for analysis, which will be used for correlative studies if a pretreatment biopsy reveals necrotic tissue.

‣ The effects of domvanalimab, zimberelimab, and APX005M on the developing human fetus are unknown. For this reason, women of child-bearing potential and men must agree to use adequate contraception (See Section 5.6) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 4 months after completion of domvanalimab, zimberelimab, or APX005M administration.

⁃ Women of childbearing potential (WOCBP), defined as not surgically sterilized and between menarche and 1-year post menopause, must have a negative serum pregnancy test within 7 days prior to the first dose of investigational therapies and a negative urine (or serum) pregnancy test within 3 days prior to the first dose of investigational therapies.

⁃ WOCBP must agree to use highly effective methods of contraception from the time of consent, through the duration of study treatment, and 5 months after the last dose of investigational therapies.

⁃ Male participants with WOCBP sexual partners must agree to use highly effective methods of contraception, and to refrain from donating sperm from the time of consent through the duration of study treatment and 7 months after the last dose of investigational therapies. Contraceptive requirements may be extended depending on local regulatory requirements.

⁃ Female participants must not be breast feeding and must not breast-feed a baby while on treatment and for up to 7 months after the last dose of investigational therapies.

• Ability to understand and the willingness to sign a written informed consent document.

• Willing and able to comply with the requirements and restrictions in this protocol.

• Eligibility Criteria for Stage 2 (Crossover Stage)

‣ Patients must meet all of the criteria used for Stage 1.

⁃ Patients allocated to the control arm (Arm B) during Stage 1 have the ability to initiate Stage 2 treatment within 4 weeks after experiencing disease progression per RECIST v1.1 while receiving control treatment

• Availability of a tumor specimen from on-treatment biopsy during Expansion Phase. If this is not available, willingness to undergo biopsy prior to initiation of Crossover Phase.