A Study of ASP1948, Targeting an Immune Modulatory Receptor as a Single Agent and in Combination With a PD-l Inhibitor (Nivolumab or Pembrolizumab) in Subjects With Advanced Solid Tumors

NCT03565445 | Completed Phase 1 FDA Drug

• 5 other identifiers: 1948-CL-01012018-003873-82KEYNOTE-A87jRCT2031200341MK-3475-A87
• Study Type: interventional
• Target: 190
• Locations: 9 countries
• Sites: 42

Brief Summary

The purpose of this study is to evaluate the tolerability and safety profile of ASP1948 when administered as a single agent and in combination with nivolumab or pembrolizumab in participants with locally advanced (unresectable) or metastatic solid tumors; characterize the pharmacokinetic profile of ASP1948 when administered as a single agent and in combination with nivolumab or pembrolizumab and determine the recommended Phase 2 dose (RP2D) of ASP1948 when administered as a single agent and in combination with nivolumab or pembrolizumab. This study will also evaluate the antitumor effect of ASP1948 when administered as a single agent and in combination with nivolumab or pembrolizumab.

Conditions

Advanced Solid Tumors

Keywords

NSCLC; Tumors; squamous cell carcinoma of the head and neck (SCCHN); Oncology; breast cancer; ASP1948; mCRPC; ovarian cancer; Locally advanced or metastatic solid tumor malignancies; pancreatic cancer; Advanced solid tumors

Outcome Measures

Primary Outcomes (25)

• Number of Participants with Dose Limiting Toxicities (DLTs)

  DLT is any AE that cannot be attributed 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 requires transfusion Gr 4 anemia or Gr 3 anemia requiring transfusion Gr ≥ 3 NHAE Gr ≥ 2 pneumonitis 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) Gr ≥ 2 encephalopathy, meningitis, or motor or sensory neuropathy Gr ≥ 2 pulmonary or CNS hemorrhage Gr ≥ 3 hemorrhage GBS or MS/MG IRR leading to infusion discontinuation Prolonged delay in initiating cycle 2 due to TRT Any TRT that caused participant to discontinue treatment during DLT period Missing \>25% of ASP1948 or pembrolizumab doses as a result of drug-related AE(s) during DLT period Gr 5 toxicity.

  Up to 28 days

• Number of Participants with Adverse Events (AEs)

  An AE is 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 \& 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 resulted 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 is defined as an AE observed after starting administration of the study drug.

  From first dose until 90 days after last dose (up to 823 days)

• Number of Participants with Immune-related AEs

  Immune-related AEs observed with currently approved checkpoint inhibitors (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). TEAE is defined as an AE observed after starting administration of the study drug.

  From first dose until 30 days after last dose (up to 763 days)

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

  The ECOG is 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. Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

  End of Treatment (Baseline up to 733 days)

• Pharmacokinetics (PK) of ASP1948 (Cycle 1): Area Under The Concentration-Time Curve From The Time Zero to The Last Measurable Concentration (AUClast)

  AUClast is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): AUClast

  AUClast is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Area Under the Concentration-Time Curve From the Time of Dosing Extrapolated to Time Infinity (AUCinf)

  AUCinf is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Percentage of AUCinf Due to Extrapolation From Time of The Last Measurable Concentration To Time Infinity (AUCinf %extrap)

  AUCinf %extrap is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Area Under The Concentration-Time Curve From The Time of Dosing to The Start of Next Dosing Interval (AUCtau)

  AUCtau is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Maximum Concentration (Cmax)

  Cmax is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): Cmax

  Cmax is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): Trough Concentration (Ctrough)

  Ctrough is derived from the PK serum samples collected.

  Cycle 10: Predose

• PK of ASP1948 (Cycle 1): Time of The Maximum Concentration (tmax)

  tmax is derived from the PK serum samples collected

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): tmax

  tmax is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): AUCtau

  AUCtau is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Terminal Elimination Half-Life ( t1/2)

  t1/2 is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Time of Last Measurable Concentration (tlast)

  tlast is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): Terminal Elimination Half-Life ( t1/2)

  t1/2 is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): tlast

  tlast is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Total Clearance (CL) after Intravenous Dosing

  CL is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): CL after Intravenous Dosing

  CL is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Volume of Distribution During the Terminal Elimination Phase (Vz) After Intravenous Dosing

  Vz is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): Vz After Intravenous Dosing

  Vz is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 1): Apparent Volume of Distribution at Steady State (Vss) after Intravenous Dosing

  Vss is derived from the PK serum samples collected.

  Cycle 1: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

• PK of ASP1948 (Cycle 10): Vss After Intravenous Dosing

  Vss is derived from the PK serum samples collected.

  Cycle 10: pre-dose, within 20 minutes after end of dosing, 4 hours, 24 hours, 48 hours, 168 hours post dose

Secondary Outcomes (8)

• Objective Response Rate (ORR) as per RECIST V1.1

  From start of study until radiographical progression or date of censoring (maximum treatment duration: up to 733 days)

• ORR as per iRECIST V1.1

  From start of study until radiographical progression or date of censoring (maximum treatment duration: up to 733 days)

• Duration of Response (DOR) 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 treatment duration: up to 733 days)

• DOR as per iRECIST

  From the date of the first response CR/PR to the date of radiographical progression or date of censoring (maximum treatment duration: up to 733 days)

• Persistence of response after discontinuation per RECIST V1.1

  From date of treatment discontinuation to the date of radiographical progression or date of censoring (maximum duration: up to 733 days)

Study Arms (13)

ASP1948 70 mg Monotherapy Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 70 mg intravenously, on day 1 of every 2-week (Q2W) cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 200 mg Monotherapy Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 200 mg intravenously, on day 1 of Q2W cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 700 mg Monotherapy Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 700 mg intravenously, on day 1 of every 2 week cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 1200 mg Monotherapy Dose Expansion

EXPERIMENTAL

Participants have received ASP1948 1200 mg intravenously, on day 1 of every 2 week cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 2000 mg Monotherapy Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 2000 mg intravenously, on day 1 of every 2 week cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 3000 mg Monotherapy Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 3000 mg intravenously, on day 1 of every 3-week (Q3W) cycle for a period of up to 16 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 16 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 2000 mg Monotherapy Dose Expansion

EXPERIMENTAL

Participants have received ASP1948 2000 mg intravenously, on day 1 of Q2W cycle for a period of up to 24 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948

ASP1948 1200 mg + Nivolumab 240 mg CT Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 1200 mg intravenously in combination with nivolumab 240 mg administered as a 30 minute intravenous infusion, on day 1 of Q2W cycle for a period of up to 24 cycles or until a discontinuation criterion is met. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948; Drug: nivolumab

ASP1948 2000 mg+ Nivolumab 240 mg CT Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 2000 mg intravenously in combination with nivolumab 240 mg administered as a 30 minute intravenous infusion, on day 1 of Q2W cycle for a period of up to 24 cycles or until a discontinuation criterion is met. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948; Drug: nivolumab

ASP1948 2000 mg + Nivolumab 240 mg CT Dose Expansion

EXPERIMENTAL

Participants have received ASP1948 2000 mg intravenously in combination with nivolumab 240 mg administered as a 30 minute intravenous infusion, on day 1 of every 2 week cycle for a period of up to 24 cycles or until a discontinuation criterion is met. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 24 cycles or until a discontinuation criteria is met.

Drug: ASP1948; Drug: nivolumab

ASP1948 2000 mg + Pembrolizumab 400 mg CT Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 2000 mg intravenously on day 1 of Q2W cycle in combination with pembrolizumab 400 mg administered as a 30 minute intravenous infusion, on day 1, once every 6 weeks (Q6W) for a period of up to 24 cycles or until a discontinuation criterion is met. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 24 cycles or until a discontinuation criteria is met. Participants who completed 24 cycles of treatment and have entered the follow-up period with PR or SD are allowed to continue on pembrolizumab alone for a period of up to an additional 10 doses of pembrolizumab. If the participant is eligible for a re-treatment period during follow up, administration of pembrolizumab alone is discontinued and combination therapy with ASP1948 is resumed per the protocol.

Drug: ASP1948; Drug: pembrolizumab

ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Escalation

EXPERIMENTAL

Participants have received ASP1948 3000 mg intravenously in combination with pembrolizumab 200 mg administered as a 30 minute intravenous infusion, on day 1 of Q3W cycle for a period of up to 16 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 16 cycles or until a discontinuation criteria is met. Participants who completed 16 cycles of treatment and have 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 is eligible for a re-treatment period during follow up, administration of pembrolizumab alone is discontinued and combination therapy with ASP1948 is resumed per the protocol.

Drug: ASP1948; Drug: pembrolizumab

ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Expansion

EXPERIMENTAL

Participants have received ASP1948 3000 mg intravenously in combination with pembrolizumab 200 mg administered as a 30 minute intravenous infusion, on day 1 of Q3W cycle for a period of up to 16 cycles or until a discontinuation criterion is met during treatment period. Qualifying participants have entered a re-treatment period and have received combination treatment for an additional 16 cycles or until a discontinuation criteria is met. Participants who completed 16 cycles of treatment and have 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 is eligible for a re-treatment period during follow up, administration of pembrolizumab alone is discontinued and combination therapy with ASP1948 is resumed per the protocol.

Drug: ASP1948; Drug: pembrolizumab

Interventions

ASP1948 DRUG

Intravenously (IV)

ASP1948 1200 mg + Nivolumab 240 mg CT Dose Escalation; ASP1948 1200 mg Monotherapy Dose Expansion; ASP1948 200 mg Monotherapy Dose Escalation; ASP1948 2000 mg + Nivolumab 240 mg CT Dose Expansion; ASP1948 2000 mg + Pembrolizumab 400 mg CT Dose Escalation; ASP1948 2000 mg Monotherapy Dose Escalation; ASP1948 2000 mg Monotherapy Dose Expansion; ASP1948 2000 mg+ Nivolumab 240 mg CT Dose Escalation; ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Escalation; ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Expansion; ASP1948 3000 mg Monotherapy Dose Escalation; ASP1948 70 mg Monotherapy Dose Escalation; ASP1948 700 mg Monotherapy Dose Escalation

nivolumab DRUG

Intravenously (IV)

ASP1948 1200 mg + Nivolumab 240 mg CT Dose Escalation; ASP1948 2000 mg + Nivolumab 240 mg CT Dose Expansion; ASP1948 2000 mg+ Nivolumab 240 mg CT Dose Escalation

pembrolizumab DRUG

Intravenously (IV)

Also known as: KEYTRUDA®

ASP1948 2000 mg + Pembrolizumab 400 mg CT Dose Escalation; ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Escalation; ASP1948 3000 mg + Pembrolizumab 200 mg CT 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, and has received all standard therapies (unless the therapy is contraindicated or intolerable) felt to provide clinical benefit.
• Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of 0, or 1.
• Subject's last dose of prior antineoplastic therapy, including any immunotherapy, was at least 21 days 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) or ALK inhibitor therapy until 4 days prior to the start of study drug administration.
• Subject has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to study drug administration.
• Subject with metastatic castration-resistant prostate cancer (mCRPC) (positive scan and/or soft tissue disease documented by computed tomography/magnetic resonance imaging) 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 as indicated by laboratory values. (If a subject has received a recent blood transfusion, the laboratory tests must be obtained ≥ 28 days after any blood transfusion.) Subjects can be on a stable dose of erythropoietin (≥ approximately 3 months). Note: Growth factors, colony stimulating factors are not permitted in the screening period.
• Female subject must either:
• Be of non-childbearing potential: post-menopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or; documented surgically sterile (e.g., hysterectomy, bilateral salpingectomy, bilateral oophorectomy).
• Or, if of childbearing potential: Agree not to try to become pregnant during the study treatment and for 6 months after the final study drug administration; and have a negative urine or serum pregnancy test prior to study drug administration; and if heterosexually active, agree to consistently use 1 form of highly effective birth control starting at screening and throughout the study treatment and 6 months after the final study drug administration.
• Female subject must agree not to breastfeed starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
• Female subject must not donate ova starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
• A sexually active male subject with female partner(s) who are of childbearing potential is eligible if :
• The male subject agrees to use a male condom starting at screening and continues throughout the study treatment, and for 6 months after the final study drug administration.

You may not qualify if:

• Subject weighs \< 45 kg.
• Subject has received investigational therapy (other than an investigational epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) in a subject with EGFR mutations or ALK inhibitor in a subject with an ALK mutation) within 21 days 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, 2 mg per day of dexamethasone or up to 10 mg per day of prednisone) are allowed. Note: Corticosteroids for prophylaxis (e.g., contrast dye allergy) or for brief treatment of conditions not related to study treatment (e.g., delayed-type hypersensitivity reaction caused by a contact allergen) is also 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 the subject is clinically stable and has no evidence of CNS progression by imaging for at least 28 days prior to start of study treatment and are not requiring immunosuppressive doses of systemic steroids (\> 30 mg per day of hydrocortisone, \> 2 mg per day of dexamethasone or \> 10 mg per day of prednisone or equivalent) for longer than 14 days.
• Subject has leptomeningeal disease as a manifestation of the current malignancy.
• Subject has an active autoimmune disease that has required systemic treatment in the past 2 years. Subjects with type 1 diabetes mellitus, stable endocrinopathies maintained on appropriate replacement therapy and 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 ASP1948, nivolumab or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
• Subject with positive Hepatitis B virus antibodies and surface antigen (indicating acute Hepatitis B virus (HBV) or chronic HBV) or Hepatitis C (HCV ribonucleic acid (RNA) \[(qualitative or quantitative)\]. Hepatitis C RNA testing is not required in subjects with negative Hepatitis C antibody testing. Hepatitis B virus antibodies are not required in subjects with negative Hepatitis B surface antigen.
• 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 active infection requiring systemic therapy within 14 days prior to study drug treatment.
• Subject is expected to require another form of antineoplastic therapy while on study treatment.
• Subject has an uncontrolled intercurrent illness including, but not limited to cardiac arrhythmia or psychiatric illness/social situations that would limit compliance with study requirements.
• Subject's AEs (excluding alopecia) from prior therapy have not improved to Grade 1 or baseline within 14 days prior to start of study treatment.

Sponsors & Collaborators

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

Study Sites (42)

Yale Center for Clinical Investigation

New Haven, Connecticut, 06520-8028, United States

Location

Norton Cancer Institute

Louisville, Kentucky, 40202, United States

Location

Cancer Center at Greater Baltimore Medical

Baltimore, Maryland, 21153, United States

Location

University of Michigan Comprehensive Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68310, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

UPMC- Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Sarah Cannon Research Institute - SCRI

Nashville, Tennessee, 37203, United States

Location

Henry-Joyce Cancer Center

Nashville, Tennessee, 37232, United States

Location

Mary Crowley Cancer Research Center

Dallas, Texas, 75230, United States

Location

South Texas Accelerated Research Therapeutics

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Care Specialist, PC

Fairfax, Virginia, 22031, United States

Location

University of Washington-Seattle Cancer Care Alliance

Seattle, Washington, 98109, United States

Location

Site CA15002

Edmonton, Canada

Location

Site CA15004

Montreal, Canada

Location

Site IT39008

Milan, Italy

Location

Site IT39006

Modena, Italy

Location

Site JP81002

Chiba, Japan

Location

Site JP81001

Tokyo, Japan

Location

Site PT35104

Porto, Portugal

Location

Site KR82001

Seoul, South Korea

Location

Site KR82002

Seoul, South Korea

Location

Site KR82003

Seoul, South Korea

Location

Site KR82004

Seoul, South Korea

Location

Site KR82005

Seoul, South Korea

Location

Site KR82006

Seoul, South Korea

Location

Site KR82007

Seoul, South Korea

Location

Site ES34002

Barcelona, Spain

Location

Site ES34006

Barcelona, Spain

Location

Site ES34010

Barcelona, Spain

Location

Site ES34014

Barcelona, Spain

Location

Site ES34003

Cataluna, Spain

Location

Site ES34004

Cataluna, Spain

Location

Site ES34007

Madrid, Spain

Location

Site ES34012

Madrid, Spain

Location

Site TW88601

Taipei, Taiwan

Location

Site TW88602

Taipei, Taiwan

Location

Site GB44006

Manchester, United Kingdom

Location

Related Publications (1)

• Bao R, Surriga O, Olson DJ, Allred JB, Strand CA, Zha Y, Carll T, Labadie BW, Bastos BR, Butler M, Hogg D, Musi E, Ambrosini G, Munster P, Schwartz GK, Luke JJ. Transcriptional analysis of metastatic uveal melanoma survival nominates NRP1 as a therapeutic target. Melanoma Res. 2021 Feb 1;31(1):27-37. doi: 10.1097/CMR.0000000000000701.

  PMID: 33170593 DERIVED

Related Links

• Link to plain language summary of the study on the Trial Results Summaries website

MeSH Terms

Conditions

Neoplasms; Squamous Cell Carcinoma of Head and Neck; Breast Neoplasms; Ovarian Neoplasms; Pancreatic Neoplasms

Interventions

Nivolumab; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms by Site; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Digestive System Neoplasms; Digestive System Diseases; Pancreatic Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Medical Monitor

  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: May 25, 2018
• First Posted: June 21, 2018
• Study Start: July 2, 2018
• Primary Completion: March 27, 2023
• Study Completion: March 27, 2023
• Last Updated: November 1, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
• Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.

Locations

JP (2); KR (7); CA (2); TW (2); IT (2); GB (1); US (17); PT (1); ES (8)