Participants received 1200 mg ASP1948 intravenously, on day 1 of cycle 1 and 2 followed by once every 2 weeks (Q2W) until discontinuation criteria or up to 2 years. Each cycle duration was 14 days.

Participants received 2000 mg ASP1948 intravenously, on day 1 of cycle 1 and 2 followed by once Q2W until discontinuation criteria or up to 2 years. Each cycle duration was 14 days.

Participants received 3000 mg ASP1948 intravenously, on day 1 of cycle 1 followed by once every 3 weeks until discontinuation criteria or up to 2 years. Each cycle duration was 21 days.

ASP1948

Central Contact

The primary purpose of this study is to evaluate the tolerability, safety and pharmacokinetic profile of ASP1948 in Japanese patients with locally advanced (unresectable) or metastatic solid tumors.

This study will also evaluate the antitumor effect of ASP1948.

This study consists of 3 dose levels (1200 milligrams \[mg\], 2000 mg and 3000 mg) and enrollment of subjects into dose level 1200 mg will take place first. Dose level 2000 mg would only be opened if dose level 1200 mg is deemed tolerable. Dose level 3000 mg would only be opened if dose level 2000 mg is deemed tolerable.

Study of ASP1948, Targeting an Immune Modulatory Receptor, in Japanese Patients With Advanced Solid Tumors

A Phase 1, Open-label Study of ASP1948, Targeting an Immune Modulatory Receptor, in Japanese Patients With Advanced Solid Tumors

Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."

DLT is graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 4.03. The DLT observation period may be increased if deemed appropriate by Dose Escalation and Safety Committee.

DLT is graded using NCI-CTCAE Version 4.03. The DLT observation period may be increased if deemed appropriate by Dose Escalation and Safety Committee.

An AE is any untoward medical occurrence in a subject administered an investigational product (IP) and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IP whether or not considered related to the IP.

Number of participants with potentially clinically significant irAEs. irAEs 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).

Number of participants with potentially clinically significant IRRs. The majority of IRRs to monoclonal antibodies represent "standard" infusion reactions, and the most common manifestations of these standard infusion reactions include: fever and/or shaking/chills; flushing and/or itching; changes in heart rate and blood pressure; shortness of breath or chest discomfort; pain in back or abdomen; nausea, vomiting and/or diarrhea and skin rash (various types). Fever and muscle pain suggest that the reaction is a standard infusion reaction.

Adverse event (AE) is considered "serious" if the investigator or sponsor view any of the following outcomes: Death, life-threatening, persistent or significant disability/incapacity, congenital anomaly or birth defect, hospitalization, or medically important event.

Number of participants with potentially clinically significant CBC values.

Number of participants with potentially clinically significant serum chemistry values.

Number of participants with potentially clinically significant urinalysis values.

Number of participants with potentially clinically significant PT/INR values.

Number of participants with potentially clinically significant aPTT values.

Number of participants with potentially clinically significant TSH values.

Number of participants with potentially clinically significant free T4 values.

Number of participants with potentially clinically significant ECG values.

Number of participants with potentially clinically significant vital sign values.

Number of participants with potentially clinically significant physical exams values.

The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 4 (completely disabled). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.

AUClast will be recorded from the PK serum samples collected.

AUCinf will be recorded from the PK serum samples collected.

AUCinf(%extrap) will be recorded from the PK serum samples collected.

AUCtau will be recorded from the PK serum samples collected.

Cmax will be recorded from the PK serum samples collected.

Ctrough will be recorded from the PK serum samples collected.

tmax will be recorded from the PK serum samples collected.

t1/2 will be recorded from the PK serum samples collected.

tlast will be recorded from the PK serum samples collected.

CL will be recorded from the PK serum samples collected.

V will be recorded from the PK serum samples collected.

Tumor size is defined as the sum of the diameters of all target lesions per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The percent change from baseline in tumor size will be calculated for subjects with target lesions at baseline. The best percent change in tumor size is the maximum percent reduction from baseline, or if the subject has no reduction in size, the minimum percent increase from baseline.

BOR is defined as the best response recorded from the start of the study treatment until the end of treatment.

Astellas Pharma Inc

Neoplasms

All Conditions

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Rare Diseases

Carcinoma

Breast Neoplasms

Pancreatic Neoplasms

Carcinoma, Squamous Cell

Squamous Cell Carcinoma of Head and Neck

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

nivolumab

pembrolizumab

Medical Monitor

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.

This is a dose-escalation and expansion study of ASP1948 as a single agent and in combination with nivolumab or pembrolizumab. The study consists of 3 periods for monotherapy and combination therapy: screening, treatment and follow up, followed by an optional Re-treatment period for participants that qualify.

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.

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

A Phase 1b 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

Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.

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.

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.

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.

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.

AUClast is derived from the PK serum samples collected.

AUCinf is derived from the PK serum samples collected.

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

AUCtau is derived from the PK serum samples collected.

Cmax is derived from the PK serum samples collected.

Ctrough is derived from the PK serum samples collected.

tmax is derived from the PK serum samples collected

tmax is derived from the PK serum samples collected.

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

tlast is derived from the PK serum samples collected.

CL is derived from the PK serum samples collected.

Vz is derived from the PK serum samples collected.

Vss is derived from the PK serum samples collected.

ORR as per RECIST 1.1 is defined as the percentage of participants for each dose level whose best overall response is rated as confirmed CR or PR. CR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

ORR as per iRECIST is defined as the percentage of participants for each dose level whose best overall response is rated as confirmed iCR or iPR. iCR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. iPR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

DOR as per RECIST 1.1 is defined as the time from the date of the first response CR/PR (whichever is first recorded) to the date of radiographical progression or date of censoring. CR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR is defined as at least a 30% decrease in the sum of diameters (longest for non nodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

DOR as per iRECIST is defined as the time from the date of the first response iCR/iPR (whichever is first recorded) to the date of radiographical progression or date of censoring. iCR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. iPR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

Persistence of response as per RECIST 1.1 is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring. Persistence of response is derived for participants who at the time of treatment discontinuation had a confirmed response of CR or PR based on RECIST 1.1. CR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

Persistence of response as per iRECIST is defined as the time from the date of treatment discontinuation to the date of radiographical progression or date of censoring. Persistence of response is derived for participants who at the time of treatment discontinuation had a confirmed response of iCR or iPR. iCR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. iPR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters.

DCR as per RECIST 1.1 is defined as percentage of participants for each dose level whose BOR is rated as confirmed CR, PR or Stable Disease (SD). CR is defined as disappearance of all target and nontarget lesions. Any pathological lymph nodes (whether target or nontarget) must have reduction in short axis to \< 10 mm from baseline measurement. PR is defined as at least a 30% decrease in the sum of diameters (longest for nonnodal lesions, short axis for nodal lesions) of target lesions taking as reference to the baseline sum of diameters. SD is defined as neither sufficient decrease to qualify for PR nor sufficient increase to qualify for progressive disease taking as reference the smallest sum of diameters. Progressive disease (PD): \>= 20% increase in sum of diameters of target lesions taking as reference the smallest sum, and sum must also demonstrate an absolute increase of \>= 5 mm. Appearance of 1 or more new lesions is also considered progression.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of ASP1948, Targeting an Immune Modulatory Receptor, in Japanese Patients With Advanced Solid Tumors	NCT04094506	Locally Advance...	ASP1948	20 Years -	Astellas Pharma Inc
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	Advanced Solid ...	ASP1948 nivolumab pembrolizumab	18 Years -	Astellas Pharma Inc
Study of ASP1948, Targeting an Immune Modulatory Receptor, in Japanese Patients With Advanced Solid Tumors	NCT04094506	Locally Advance...	ASP1948	20 Years -	Astellas Pharma Inc

Spots Global Cancer Trial Database for asp1948

Every month we try and update this database with for asp1948 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for asp1948

Every month we try and update this database with for asp1948 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for asp1948 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.