A Multiple-dose Study of ASP8374, an Immune Checkpoint Inhibitor, as a Single Agent and in Combination With Pembrolizumab in Subjects With Advanced Solid Tumors

NCT03260322 | Completed Phase 1 FDA Drug

• 3 other identifiers: 8374-CL-01012018-001146-34KEYNOTE KN-A72
• Study Type: interventional
• Target: 169
• Locations: 9 countries
• Sites: 54

Brief Summary

The primary purpose of this study is to evaluate the tolerability and safety profile of ASP8374 when administered as a single agent and in combination with pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumor malignancies. Also primary purpose is to characterize the pharmacokinetic profile of ASP8374 when administered as a single agent and in combination with pembrolizumab. Last primary purpose of this study is to determine the recommended Phase 2 dose (RP2D) of ASP8374 when administered as a single agent and in combination with pembrolizumab. The secondary purpose of this study is to evaluate the anti-tumor effect (objective response rate \[ORR\], duration of response \[DOR\], persistence of response after discontinuation, and disease control rate \[DCR\]) of ASP8374 when administered as a single agent and in combination with pembrolizumab. NTP: Neutropenia NHAE:Non-haematological AE GBS: Guillain-Barré syndrome"" IRR: Infusion-related reaction AST: Aspartate aminotransferase ALT: Alanine aminotransferase MS/MG: Myasthenia Syndrome/Myasthenia Gravis TRT: Treatment-related Toxicity TCP: Thrombocytopenia

Conditions

Advanced Solid Tumors

Keywords

Pembrolizumab; Oncology; Tumors; ASP8374; Locally advanced or metastatic solid tumor malignancies

Outcome Measures

Primary Outcomes (21)

• Number of Participants with Dose Limiting Toxicities (DLTs)

  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

  Up to 21 Days (For ASP8374 0.5 mg: Up to 7 days)

• Number of Participants with Treatment Emergent Adverse Events (TEAEs)

  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.

  From first dose up to 90 days after last dose (maximum duration: 938 days)

• Number of Participants with Infusion Related Reactions

  Number of participants with infusion related reactions are reported.

  From first dose up to 90 days after last dose (maximum duration: 938 days)

• Number of Participants with Immune- Related Treatment Emergent Adverse Events (IrTEAEs)

  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).

  From first dose up to 90 days after last dose (maximum duration: 938 days)

• Number of Participants with Eastern Cooperative Oncology Group (ECOG) Performance status

  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.

  End of treatment ASP8374 (Up to 427 days)

• Pharmakokinetics (PK) of ASP8374 (Cycle 1): Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) (Monotherapy Dose Escalation Cohort)

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

  Cycles 1: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• Pharmakokinetics (PK) of ASP8374 (Cycle 7): Area Under the Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUClast) (Monotherapy Dose Escalation Cohort)

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

  Cycles 7: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Area Under the Concentration-Time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf) (Monotherapy Dose Escalation Cohort)

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

  Cycle 1: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Percentage of AUCinf due to extrapolation from the last measurable concentration to time infinity [AUCinf(%extrap)] (Monotherapy Dose Escalation Cohort)

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

  Cycle 1: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): Area Under the Concentration-Time Curve From the Time of Dosing to the Start of the Next Dosing Interval at Multiple Dose Conditions (AUCtau) (Monotherapy Dose Escalation Cohort)

  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.

  Cycle 7: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle= 21 days)

• PK of ASP8374 (Cycle 1): Maximum Plasma concentration (Cmax) (Monotherapy Dose Escalation Cohort)

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

  Cycles 1: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): Cmax (Monotherapy Dose Escalation Cohort)

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

  Cycles 7: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): Trough concentration (Ctrough) (Monotherapy Dose Escalation Cohort)

  Trough Concentration was derived from the PK samples.

  Cycle 7: predose

• PK of ASP8374 (Cycle 1): Time of Maximum Concentration (Tmax) (Monotherapy Dose Escalation Cohort)

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

  Cycles 1: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): Tmax (Monotherapy Dose Escalation Cohort)

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

  Cycles 7: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Terminal Elimination Half-life (T1/2) of ASP8374 (Monotherapy Dose Escalation Cohort)

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

  Cycle 1: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Time of Last Measurable Concentration (tlast) (Monotherapy Dose Escalation Cohort)

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

  Cycles 1: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): tlast (Monotherapy Dose Escalation Cohort)

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

  Cycles 7: predose, end of dosing (within 20 minutes), 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Total Systemic Observed Clearance After Intravenous Dosing (CLobs) of ASP8374 (Monotherapy Dose Escalation Cohort)

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

  Cycles 1: predose, end of dosing (within 20 minutes), 4hr, 24hrt, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 1): Volume of Distribution During the Terminal Elimination Phase (Vz) after Intravenous Dosing (Monotherapy Dose Escalation Cohort)

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

  Cycle 1: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle = 21 days)

• PK of ASP8374 (Cycle 7): Apparent Volume of Distribution at Steady State (Vss) after Intravenous Dosing of ASP8374 (Monotherapy Dose Escalation Cohort)

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

  Cycle 7: predose. end of dosing, 4hr, 24hr, 48hr, 168hr, 336hr postdose (each cycle= 21 days)

Secondary Outcomes (12)

• Best Overall Response (BOR) as per RECIST as per Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1)

  From start of study until radiographical progression or date of censoring (maximum duration: 938 days)

• BOR as per immune Response Evaluation Criteria in Solid Tumors (iRECIST)

  From start of study until radiographical progression or date of censoring (maximum duration: 938 days)

• Objective Response Rate (ORR) as per RECIST v1.1

  From start of study until radiographical progression or date of censoring (maximum duration: 938 days)

• ORR as per iRECIST

  From start of study until radiographical progression or date of censoring (maximum duration: 938 days)

• Duration of Response as per RECIST v1.1

  From the date of the first response CR/PR to the date of radiographical progression or date of censoring (maximum 938 days)

Study Arms (17)

ASP8374 0.5 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 0.5 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 2 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 2 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 7 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 7 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 20 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 20 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 70 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 70 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 200 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 200 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 700 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 700 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 1400 mg - Monotherapy Dose Escalation

EXPERIMENTAL

Participants received ASP8374 1400 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 1400 mg - Monotherapy Dose Expansion

EXPERIMENTAL

Participant received ASP8374 1400 mg intravenously, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met during treatment period. Qualifying participants entered re-treatment period and received treatment for an additional 16 cycles or until a discontinuation criteria was met.

Drug: ASP8374

ASP8374 20 mg - Combination Dose Escalation

EXPERIMENTAL

Participants received ASP8374 20 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 70 mg - Combination Dose Escalation

EXPERIMENTAL

Participants received ASP8374 70 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 200 mg - Combination Dose Escalation

EXPERIMENTAL

Participants received ASP8374 200 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 700 mg - Combination Dose Escalation

EXPERIMENTAL

Participants received ASP8374 700 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 1400 mg - Combination Dose Escalation

EXPERIMENTAL

Participants received ASP8374 1400 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 200 mg - Combination Dose Expansion

EXPERIMENTAL

Participants received ASP8374 200 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 700 mg - Combination Dose Expansion

EXPERIMENTAL

Participants received ASP8374 700 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

ASP8374 1400 mg - Combination Dose Expansion

EXPERIMENTAL

Participants received ASP8374 1400 mg intravenously in combination with pembrolizumab 200 mg adminstered as a 30 minutes intravenous infusion, on day 1 of every 3 week cycle for a period of up to 16 cycles or until a discontinuation criterion was met. Qualifying participants received combination treatment for an additional 16 cycles or until a discontinuation criteria was met. Participants who completed 16 cycles of combination treatment who entered the follow-up period with PR or SD were allowed to continue on pembrolizumab alone for a period of up to an additional 19 cycles. If the participant was eligible for the re-treatment period during follow up, administration of pembrolizumab alone was discontinued and combination therapy with ASP8374 was resumed per the protocol.

Drug: ASP8374; Drug: Pembrolizumab

Interventions

ASP8374 DRUG

intravenous

ASP8374 0.5 mg - Monotherapy Dose Escalation; ASP8374 1400 mg - Combination Dose Escalation; ASP8374 1400 mg - Combination Dose Expansion; ASP8374 1400 mg - Monotherapy Dose Escalation; ASP8374 1400 mg - Monotherapy Dose Expansion; ASP8374 2 mg - Monotherapy Dose Escalation; ASP8374 20 mg - Combination Dose Escalation; ASP8374 20 mg - Monotherapy Dose Escalation; ASP8374 200 mg - Combination Dose Escalation; ASP8374 200 mg - Combination Dose Expansion; ASP8374 200 mg - Monotherapy Dose Escalation; ASP8374 7 mg - Monotherapy Dose Escalation; ASP8374 70 mg - Combination Dose Escalation; ASP8374 70 mg - Monotherapy Dose Escalation; ASP8374 700 mg - Combination Dose Escalation; ASP8374 700 mg - Combination Dose Expansion; ASP8374 700 mg - Monotherapy Dose Escalation

Pembrolizumab DRUG

intravenous

Also known as: Keytruda

ASP8374 1400 mg - Combination Dose Escalation; ASP8374 1400 mg - Combination Dose Expansion; ASP8374 20 mg - Combination Dose Escalation; ASP8374 200 mg - Combination Dose Escalation; ASP8374 200 mg - Combination Dose Expansion; ASP8374 70 mg - Combination Dose Escalation; ASP8374 700 mg - Combination Dose Escalation; ASP8374 700 mg - Combination Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy as well as:
• Subject in the escalation cohort has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit for the subject's specific tumor type. OR
• Subject in an expansion cohort has received at least one standard therapy for the subject's specific tumor type.
• For Korea, Italy and Portugal only: Subject has locally-advanced (unresectable) or metastatic solid tumor malignancy (no limit to the number of prior treatment regimens) that is confirmed by available pathology records or current biopsy and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit for the subject's specific tumor type.
• Subject has an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1 or 2.
• Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of study drug administration. A subject with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) mutation-positive NSCLC is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) therapy or ALK inhibitor until 4 days prior to the start of study drug administration.
• For Korea only: Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was at least 21 days or 5 half-lives, whichever is shorter, prior to initiation of study drug administration. For drugs with a half-life greater than or equal to 21 days, the investigator should consider if this washout is sufficient. A subject with epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer (NSCLC) is allowed to remain on EGFR tyrosine kinase inhibitor (TKI) therapy until 7 days prior to the start of study drug administration.
• Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 2 weeks prior to study drug administration.
• Subject's adverse events (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of study treatment.
• Subject with metastatic castration resistant prostate cancer (mCRPC) (positive bone scan and/or soft tissue disease documented by computed tomography (CT) / magnetic resonance imaging (MRI)) meets both of the following:
• Subject has serum testosterone ≤ 50 ng/dL at screening.
• Subject has had an orchiectomy or plans to continue androgen deprivation therapy (ADT) for the duration of study treatment.
• Subject has adequate organ function prior to start of study treatment as indicated by the following laboratory values. If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 4 weeks after any blood transfusion.
• Female subject is eligible to participate if she is not pregnant and at least 1 of the following conditions applies:
• Not a woman of childbearing potential (WOCBP)

You may not qualify if:

• Subject weighs \< 45 kg at screening.
• Subject has received investigational therapy (other than an investigational epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in a subject with EGFR activating mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days or 5 half-lives, whichever is shorter, prior to start of study drug.
• Subject requires or has received systemic steroid therapy or any other immunosuppressive therapy within 14 days prior to study drug administration. Subjects using a physiologic replacement dose of hydrocortisone or its equivalent (defined as up to 30 mg per day of hydrocortisone up to 10 mg per day of prednisone) are allowed.
• Subject has symptomatic central nervous system (CNS) metastases or subject has evidence of unstable CNS metastases even if asymptomatic (e.g., progression on scans). Subjects with previously treated CNS metastases are eligible, if subject is clinically stable and have no evidence of CNS progression by imaging for at least 4 weeks prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (\> 30 mg per day of hydrocortisone or \> 10 mg per day of prednisone or equivalent) for longer than 2 weeks.
• Subject has an active autoimmune disease. Subjects with type 1 diabetes mellitus, endocrinopathies stably maintained on appropriate replacement therapy, or skin disorders (e.g., vitiligo, psoriasis, or alopecia) not requiring systemic treatment are allowed.
• Subject was discontinued from prior immunomodulatory therapy due to a grade ≥ 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
• Subject has known history of serious hypersensitivity reaction to a known ingredient of ASP8374 or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
• Subject has a known history of Human Immunodeficiency Virus.
• Subject with positive for Hepatitis B virus (HBV) antibodies and surface antigen (including acute HBV or chronic HBV) or Hepatitis C (\[HCV\]; ribonucleic acid \[RNA\] detected by qualitative assay). Hepatitis C RNA testing is not required in subjects with negative Hepatitis C antibody testing.
• Subject has received a live vaccine against infectious diseases within 28 days prior to initiation of study treatment.
• Subject has a history of drug-induced pneumonitis (interstitial lung disease), a history of (non-infectious) pneumonitis that required steroids, radiation pneumonitis or currently has pneumonitis.
• Subject has an infection requiring systemic therapy within 14 days prior to study drug treatment.
• Subject has received a prior allogeneic bone marrow or solid organ transplant.
• Subject is expected to require another form of antineoplastic therapy while on study treatment.
• Subject has had a myocardial infarction or unstable angina within 6 months prior to the start of study treatment or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (54)

Honor Health Research Institute

Scottsdale, Arizona, 85258, United States

Location

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of California, Davis

Sacramento, California, 95817, United States

Location

University of California, San Francisco

San Francisco, California, 94115, United States

Location

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

Location

University of Kansas Cancer Center

Fairway, Kansas, 66205, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University Hospital of Cleveland

Cleveland, Ohio, 44106, United States

Location

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

University of Pittsburgh Cancer Institute

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Mary Crowley Research Center

Dallas, Texas, 75251, United States

Location

Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226-3522, United States

Location

Site CA15004

Edmonton, Alberta, T6G 1Z2, Canada

Location

Site CA15003

Toronto, Ontario, M4N 3M5, Canada

Location

Site CA15001

Toronto, Ontario, M5G 2M9, Canada

Location

Site CA15002

Montreal, Quebec, H3T 1E2, Canada

Location

Site IT39004

Ancona, Italy

Location

Site IT39002

Milan, Italy

Location

Site IT39003

Milan, Italy

Location

Site IT39008

Milan, Italy

Location

Site IT39009

Milan, Italy

Location

Site IT39010

Modena, Italy

Location

Site IT39005

Monza, Italy

Location

Site IT39011

Negrar, Italy

Location

Site JP81001

Chūōku, Japan

Location

Site PT35101

Lisbon, Portugal

Location

Site PT35106

Porto, Portugal

Location

Site KR82004

Goyang-si, Gyeonggi-do, 410-769, South Korea

Location

Site KR82005

Seongnam-si, Gyeonggi-do, 013620, South Korea

Location

Site KR82001

Seoul, 03080, South Korea

Location

SIte KR82002

Seoul, 120-752, South Korea

Location

Site KR82006

Seoul, South Korea

Location

Site ES34002

Barcelona, Spain

Location

Site ES34003

Barcelona, Spain

Location

Site ES34009

Barcelona, Spain

Location

Site ES34010

Barcelona, Spain

Location

Site ES34001

Madrid, Spain

Location

Site ES34006

Madrid, Spain

Location

Site ES34013

Madrid, Spain

Location

Site ES34014

Valencia, Spain

Location

Site TW88602

Taichung, 00404, Taiwan

Location

Site TW88601

Tainan, Taiwan

Location

Site TW88603

Taipei, Taiwan

Location

Site GB44003

London, United Kingdom

Location

Site GB44006

London, United Kingdom

Location

Site GB44004

Newcastle upon Tyne, United Kingdom

Location

Site GB44005

Sutton Surry, United Kingdom

Location

Related Links

• Link to results and other applicable study documents on the Astellas Clinical Trials website
• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Neoplasms

Interventions

pembrolizumab

Study Officials

• Vice President Medical Sciences - Oncology

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2017
• First Posted: August 24, 2017
• Study Start: September 8, 2017
• Primary Completion: May 10, 2022
• Study Completion: May 10, 2022
• Last Updated: April 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (19); ES (8); TW (3); IT (8); JP (1); PT (2); KR (5); GB (4); CA (4)