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
NCT ID: NCT03565445
Last Updated: 2024-11-01
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE1
190 participants
INTERVENTIONAL
2018-07-02
2023-03-27
Brief Summary
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Detailed Description
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The escalation cohorts will evaluate escalating dose levels of ASP1948 in participants with locally advanced (unresectable) or metastatic solid tumor malignancies.
After discontinuation of study drug, all participants will complete an end-of-treatment visit, along with 30-day and 90-day safety follow-up visits from the last dose of study drug.
For dose expansion, the tumor-specific cohorts will include participants with squamous cell carcinoma of the head and neck (SCCHN), non-small cell lung cancer (NSCLC), metastatic castration-resistant prostate cancer (mCRPC), ovarian cancer, pancreatic cancer and breast cancer, as well as any tumor types that respond to study drug treatment during dose escalation.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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ASP1948 70 mg Monotherapy Dose Escalation
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.
ASP1948
Intravenously (IV)
ASP1948 200 mg Monotherapy Dose Escalation
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.
ASP1948
Intravenously (IV)
ASP1948 700 mg Monotherapy Dose Escalation
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.
ASP1948
Intravenously (IV)
ASP1948 1200 mg Monotherapy Dose Expansion
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.
ASP1948
Intravenously (IV)
ASP1948 2000 mg Monotherapy Dose Escalation
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.
ASP1948
Intravenously (IV)
ASP1948 3000 mg Monotherapy Dose Escalation
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.
ASP1948
Intravenously (IV)
ASP1948 2000 mg Monotherapy Dose Expansion
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.
ASP1948
Intravenously (IV)
ASP1948 1200 mg + Nivolumab 240 mg CT Dose Escalation
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.
ASP1948
Intravenously (IV)
nivolumab
Intravenously (IV)
ASP1948 2000 mg+ Nivolumab 240 mg CT Dose Escalation
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.
ASP1948
Intravenously (IV)
nivolumab
Intravenously (IV)
ASP1948 2000 mg + Nivolumab 240 mg CT Dose Expansion
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.
ASP1948
Intravenously (IV)
nivolumab
Intravenously (IV)
ASP1948 2000 mg + Pembrolizumab 400 mg CT Dose Escalation
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.
ASP1948
Intravenously (IV)
pembrolizumab
Intravenously (IV)
ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Escalation
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.
ASP1948
Intravenously (IV)
pembrolizumab
Intravenously (IV)
ASP1948 3000 mg + Pembrolizumab 200 mg CT Dose Expansion
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.
ASP1948
Intravenously (IV)
pembrolizumab
Intravenously (IV)
Interventions
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ASP1948
Intravenously (IV)
nivolumab
Intravenously (IV)
pembrolizumab
Intravenously (IV)
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* 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.
* The male subject has not had a vasectomy or is not sterile, as defined below and the subject's female partner(s) is utilizing 1 form of highly effective birth control starting at screening and continuing throughout the study treatment and for 6 months after the final study drug administration.
* Male subject must not donate sperm starting at screening and throughout the study treatment, and for 6 months after the final study drug administration.
* Male subject with a pregnant or breastfeeding partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy or time partner is breastfeeding throughout the study treatment and for 6 months after the final study drug administration.
* Subject agrees not to participate in another interventional study while receiving study drug (subjects who are currently in the follow-up period of an interventional clinical trial are allowed).
* Subject has at least 1 measurable lesion per RECIST 1.1. The measureable lesion must be outside the field of radiation if subject had prior radiotherapy. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Subjects with mCRPC who do not have measurable lesions must have at least 1 of the following:
* Progression with 2 or more new bone lesions, or
* Prostate specific antigen (PSA) progression (defined as a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination) within 6 weeks prior to study drug administration and a PSA value at the screening visit ≥ 2 ng/mL.
* Subject consents to provide available tumor specimen in a tissue block or unstained serial slides obtained within 8 to 56 days prior to first dose of study treatment. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
* Subject is an appropriate candidate for tumor biopsy and consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period. Note: This does not apply to subjects with mCRPC who do not have measurable disease.
* Subject meets one of the following:
* Subject has the tumor type for which a confirmed response was observed in a monotherapy or in combination with nivolumab dose escalation or RP2D cohort; or
* ASP1948 monotherapy or in combination with pembrolizumab expansion cohort is opened due to achieving predicted efficacious exposure, subject has squamous cell carcinoma of the head and neck (SCCHN); or
* RP2D monotherapy cohort is opened and subject has NSCLC, mCRPC, ovarian cancer, pancreatic cancer or breast cancer; or
* RP2D combination with pembrolizumab expansion cohort, is opened and subject has NSCLC (all PD-L1 status), NSCLC PD-L1 high\*, ovarian cancer, colorectal cancer, or breast cancer.
* NSCLC with PD-L1 high expressing tumor as determined by immunohistochemistry at a central laboratory during the screening period.
Subjects may be eligible for study drug re-treatment if the study remains open and the subject continues to meet all of the eligibility criteria above (except prior use of this drug) and the following conditions:
* Subject stopped initial treatment with ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab after attaining a confirmed CR or PR or SD.
* Subject experienced a confirmed disease progression by iRECIST (iCPD) after stopping their initial treatment with ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.
* Subject did not receive any prohibited anti-cancer treatment since the last dose of ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.
* Subject did not experience a toxicity that met the discontinuation criteria during the initial treatment with ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab.
Exclusion Criteria
* 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.
* Subject has significant cardiovascular disease including:
* Subject has inadequately controlled hypertension (defined as systolic blood pressure \> 150 and/or diastolic blood pressure \> 100 mmHg on antihypertensive medications).
* Subject has a history of myocardial infarction or unstable angina within 6 months prior to day 1.
* Subject has New York Heart Association Class II or greater chronic heart failure (CHF).
* History of cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 6 months prior to study treatment.
* Subject has significant vascular disease (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis) within 6 months prior to study treatment.
* Subject has a history of hemoptysis (bright red blood of ½ teaspoon or more per episode) within 12 weeks prior to study treatment.
* Subject has evidence of a bleeding diathesis or significant coagulopathy.
* Subject has inadequate recovery from prior surgical procedure or has had a major surgical procedure, open biopsy or significant traumatic injury within 28 days prior to day 1, or anticipates the need for a major surgical procedure during the course of the study or minor surgery within 7 days of starting study treatment.
* Subject has initiated new treatment with medications that affect the coagulation cascade with an international normalized ratio (INR) ≥ 2 such as vitamin K antagonists, heparins and direct thrombin inhibitors or the use of factor Xa inhibitors within 28 days prior to the start of study treatment. Note: If the subject started receiving such medications more than 28 days prior to the start of study treatment and needs to continue, this is allowed. However, new anticoagulation may not be initiated within 28 days prior to the start of study treatment.
* Subject has any condition that makes the subject unsuitable for study participation.
* Subject has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is required unless mandated by local health authority.
* Subject has had an allogeneic tissue solid organ transplant.
* Subject has known history of COVID-19 positive polymerase chain reaction (PCR) test within 4 weeks prior to start of study treatment.
* Subject has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for locally curable malignancies that have been apparently cured, which are allowed, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
* Subject has received prior treatment with a neuropilin-1 (NRP1) inhibitor.
* Subjects who have completed 40 weeks (ASP1948 monotherapy or combination therapy with nivolumab cohorts) or 57 weeks (ASP1948 combination therapy with pembrolizumab) of follow-up with disease control are not eligible for retreatment.
* Subject currently has an ongoing Adverse Event (AE) related to the initial ASP1948 or ASP1948 in combination with nivolumab or pembrolizumab treatment that meets the criteria for treatment interruption or discontinuation.
18 Years
ALL
No
Sponsors
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Merck Sharp & Dohme LLC
INDUSTRY
Astellas Pharma Global Development, Inc.
INDUSTRY
Responsible Party
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Principal Investigators
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Medical Monitor
Role: STUDY_DIRECTOR
Astellas Pharma Global Development, Inc.
Locations
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Yale Center for Clinical Investigation
New Haven, Connecticut, United States
Norton Cancer Institute
Louisville, Kentucky, United States
Cancer Center at Greater Baltimore Medical
Baltimore, Maryland, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Washington University
St Louis, Missouri, United States
Oncology Hematology West P.C. dba Nebraska Cancer Specialists
Omaha, Nebraska, United States
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, United States
Icahn School of Medicine at Mount Sinai
New York, New York, United States
University of Oklahoma
Oklahoma City, Oklahoma, United States
UPMC- Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
University of South Carolina
Charleston, South Carolina, United States
Sarah Cannon Research Institute - SCRI
Nashville, Tennessee, United States
Henry-Joyce Cancer Center
Nashville, Tennessee, United States
Mary Crowley Cancer Research Center
Dallas, Texas, United States
South Texas Accelerated Research Therapeutics
San Antonio, Texas, United States
Virginia Cancer Care Specialist, PC
Fairfax, Virginia, United States
University of Washington-Seattle Cancer Care Alliance
Seattle, Washington, United States
Site CA15002
Edmonton, , Canada
Site CA15004
Montreal, , Canada
Site IT39008
Milan, , Italy
Site IT39006
Modena, , Italy
Site JP81002
Chiba, , Japan
Site JP81001
Tokyo, , Japan
Site PT35104
Porto, , Portugal
Site KR82001
Seoul, , South Korea
Site KR82002
Seoul, , South Korea
Site KR82003
Seoul, , South Korea
Site KR82004
Seoul, , South Korea
Site KR82005
Seoul, , South Korea
Site KR82006
Seoul, , South Korea
Site KR82007
Seoul, , South Korea
Site ES34002
Barcelona, , Spain
Site ES34006
Barcelona, , Spain
Site ES34010
Barcelona, , Spain
Site ES34014
Barcelona, , Spain
Site ES34003
Cataluna, , Spain
Site ES34004
Cataluna, , Spain
Site ES34007
Madrid, , Spain
Site ES34012
Madrid, , Spain
Site TW88601
Taipei, , Taiwan
Site TW88602
Taipei, , Taiwan
Site GB44006
Manchester, , United Kingdom
Countries
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References
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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.
Related Links
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Link to plain language summary of the study on the Trial Results Summaries website
Other Identifiers
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2018-003873-82
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
KEYNOTE-A87
Identifier Type: OTHER
Identifier Source: secondary_id
jRCT2031200341
Identifier Type: REGISTRY
Identifier Source: secondary_id
MK-3475-A87
Identifier Type: OTHER
Identifier Source: secondary_id
1948-CL-0101
Identifier Type: -
Identifier Source: org_study_id
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