DLT was defined as any of the following AE that cannot clearly attribute to a cause other than study drug: Grade (Gr) 4 NTP or Gr ≥ 3 febrile NTP Gr 4 TCP; or Gr 3 TCP accompanied by bleeding that required any transfusion Gr 4 anemia or Gr 3 anemia requiring transfusion Gr ≥ 3 NHAE Gr ≥ 2 pneumonitis Gr ≥ 2 encephalopathy, meningitis, or motor or sensory neuropathy AST or ALT \> 5x upper limit of normal (ULN; Gr ≥ 3) without liver metastases AST or ALT \> 8 x ULN in participants with liver metastases AST or ALT \> 3 x ULN \& total bilirubin \> 2 x ULN (in participant with Gilbert syndrome: AST or ALT \> 3x ULN \& direct bilirubin \> 1.5 x ULN) Total bilirubin \> 3x ULN (Gr ≥ 3) GBS or MS/MG IRR that required the infusion to be discontinued Prolonged delay (\> 2 weeks) in initiating cycle 2 due to TRT Any TRT that caused the participant to discontinue treatment during cycle 1 Missing \>25% of ASP8374 or pembrolizumab doses as a result of drug-related AE(s) during the 1st cycle Gr 5 toxicity

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. An AE is considered "serious" if, it results in any of the following outcomes: results in death; is life-threatening; results in persistent or significant disability/incapacity or substantial disruption of the ability to conduct normal life functions; results in congenital anomaly, or birth defect; requires inpatient hospitalization; or leads to prolongation of hospitalization; other medically important events. TEAE was defined as an AE observed after starting administration of the study drug.

Number of participants with infusion related reactions are reported.

AEs associated with pembrolizumab exposure may represent an immune-related response. Immune-related AEs observed with currently approved check point inhibitor CPIs include rash, oral mucositis, dry mouth, colitis/diarrhea, hepatitis, pneumonitis, and endocrinopathies (hypophysitis, hypothyroidism, hyperthyroidism, adrenal insufficiency and Type 1 diabetes mellitus). Other less frequent irAEs associated with CPIs include: nephritis; pancreatitis; myositis; arthritis; neurologic toxicities (Guillain-Barre syndrome, myasthenia gravis, posterior reversible encephalopathy syndrome, aseptic meningitis, enteric neuropathy, transverse myelitis, and autoimmune encephalitis), cardiotoxicity (myocarditis and conduction abnormalities); hematologic toxicity (red cell aplasia, neutropenia, thrombo-cytopenia, acquired hemophilia A, and cryoglobulinemia); and eye inflammation (episcleritis, conjunctivitis, uveitis or orbital inflammation).

The ECOG was used to assess performance status. Number of participants in each of the ECOG PS grade were reported. 0 = Fully active, able to carry on all predisease performance without restriction; 1. Restricted in physically strenuous activity, but ambulatory and able to carry out work of a light or sedentary nature; 2. Ambulatory and capable of all self-care, but unable to carry out any work activities. Up and about more than 50% of waking hours; 3. Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4. Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair.

Area under the concentration-time curve from the time zero to the last measurable concentration was derived from the plasma samples.

Area under the concentration-time curve from the time zero to the last measurable concentration was derived from the plasma samples.

Area under the concentration-time curve from the time of dosing extrapolated to time infinity was derived from the plasma samples.

Percentage of AUCinf due to extrapolation from the last measurable concentration to time infinity was derived from the plasma samples.

AUCtau: Area under the concentration-time curve from the time of dosing to the start of the next dosing interval was derived from plasma samples.

Maximum plasma concentration of ASP8374 was derived from the plasma samples.

Maximum plasma concentration of ASP8374 was derived from the plasma samples.

Trough Concentration was derived from the PK samples.

Time of maximum plasma concentration of ASP8374 was derived from the plasma samples.

Time of maximum plasma concentration of ASP8374 was derived from the plasma samples.

Terminal half life of ASP8374 was derived from the plasma samples.

Time of last measurable concentration was derived from the plasma samples.

Time of last measurable concentration was derived from the plasma samples.

Total systemic observed clearance after intravenous dosing was derived from the plasma samples

Volume of distribution after intravenous dosing during the terminal elimination phase was derived from plasma samples.

Volume of distribution at steady state after intravenous dosing was derived from plasma samples.