This is a FIH, Phase 1, open-label, multi-center, non-randomized study. The study will consist of a dose escalation phase (Part 1) and a cohort expansion phase (Part 2).

Part 2 comprises two arms, Part 2A and Part 2B and will be initiated after the MTD/preliminary RP2D dose decision. After determination of preliminary RP2D for use in Part 2, a different dose level in Part 1 may remain open in order to further inform the dose optimization decision.

Dose Escalation and Expansion Trial with CB307, a Trispecific Humabody® T-cell Enhancer

Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [Time Frame: The nature and frequency of any DLTs during the DLT-monitoring period assessed based on NCI CTCAE v5.0. up to 20 months duration.]

Number of participants with treatment-related adverse events with CB307 in combination with pembrolizumab as assessed by CTCAE v5.0 [Time Frame: The nature and frequency of any DLTs during the DLT-monitoring period for participants with combination therapy, assessed based on NCI CTCAE v5.0. up to 20 months duration.]

Histologically confirmed diagnosis of advanced solid tumors, not amendable for standard care

PSMA positivity

Has radiologically measurable and clinically evaluable disease per RECIST v1.1

Has an Eastern Cooperative Oncology Group Performance Status ≤2

All acute toxic effects of any prior radiotherapy, chemotherapy or surgical procedure must have resolved ≤grade 1, except alopecia (any grade) and ≤grade 2 peripheral neuropathy

Has adequate hematological function

Adequate liver and renal organ function

Evidence of autoimmune or significant, uncontrolled concomitant diseases that could affect compliance with the protocol or interpretation of results

Discontinuation from anti-cytotoxic lymphocyte-associated protein 4, anti-PD1 or anti-PD-L1 antibody because of intolerable toxicity

Brain metastasis

Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent

Current or history of CNS disease that could potentially complicate the assessment of immune effector cell-associated neurotoxicity syndrome (ICANS)

Uncontrolled pleural effusion, pericardial effusion or ascites

Currently receiving bisphosphonate therapy for symptomatic hypercalcemia

Active second malignancy

Significant cardiovascular/cerebrovascular vascular disease within 6 months prior to the first dose of CB307

Known HIV-1, HBV or HCV infection

Known active or uncontrolled bacterial, viral, fungal, mycobacterial, parasitic or other infection

History of chronic liver disease or evidence of hepatic cirrhosis

Any other diseases, metabolic dysfunction, physical examination finding or clinical laboratory finding that give reasonable suspicion of a disease or condition that would contraindicate the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications

Major surgery or significant traumatic injury within 28 days prior to the first dose of CB307

Administered a live attenuated vaccine within 28 days prior to the first dose of CB307 or anticipation that such a live attenuated vaccine will be required during the study or 3 months after the last dose

Dementia or altered mental status that would prohibit informed consent

Pregnancy or breastfeeding

Known hypersensitivity to any of the components of CB307 or history of severe hypersensitivity reactions to antibodies

Adverse events (grade 1 or baseline) not recovered from previous anti-cancer treatment

Last dose with any of the following agents: etanercept, infliximab, tacrolimus, cyclosporine, mycophenolic acid, alefacept, efalizumab or similar systemic immune modulator within 28 days or 5 half-lives

Regular immunosuppressive therapy

Long-term use of systemic steroids or use of high doses of systemic corticosteroids (>10 mg of prednisone or equivalent) within 7 days prior to the first dose of CB307

Severe dyspnea at rest due to complications of advanced malignancy or requiring supplementary oxygen therapy

Prior allogeneic hematopoietic stem cell transplantation or prior solid organ transplantation