Study of ASP0739 Alone and With Pembrolizumab in Advanced Solid Tumors With NY-ESO-1 Expression Participants

• ClinicalTrials.gov Identifier: NCT04939701
• Recruitment Status: Active, not recruiting
• First Posted: June 25, 2021
• Last Update Posted: January 25, 2023
• Sponsor: Astellas Pharma Global Development, Inc.
• Information provided by (Responsible Party): Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Study Description

Brief Summary:

The purpose of this study is to evaluate the safety, and tolerability of ASP0739, when administered as a single agent and in combination with pembrolizumab.

This study will also evaluate the clinical response and other measures of anticancer activity of ASP0739 when administered as a single agent and in combination with pembrolizumab based on central and local assessment.

Condition or disease	Intervention/treatment	Phase
Ovarian Cancer; NSCLC; ESCC; Solid Tumors	Drug: ASP0739; Drug: Pembrolizumab	Phase 1; Phase 2

Detailed Description:

The study is comprised of 2 phases. Phase 1 (dose escalation) includes participants with solid tumors known to express New York esophageal squamous cell carcinoma 1 (NY-ESO-1). Phase 2 (ASP0739 as single agent and in combination with pembrolizumab) includes participants with relapsed/refractory Synovial Sarcoma (SS), myxoid/round cell liposarcoma (MRCL), and ovarian cancer who have not responded to Standard of Care (SOC) or are ineligible for standard therapy. Phase 2 single agent will also include a cohort of participants with select solid tumors known to express NY-ESO-1 (melanoma, Non Small Cell Lung Cancer-adenocarcinoma [NSCLC], squamous cell and esophageal squamous cell carcinoma [ESCC]). Japanese participants will only be enrolled into the monotherapy arm of the dose expansion cohort.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 339 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1/2 Open-label Study Investigating the Safety, Tolerability and Efficacy of ASP0739 as a Single Agent and in Combination With Pembrolizumab in Patients With Advanced Solid Tumors Known to Express NY-ESO-1
• Actual Study Start Date: January 11, 2022
• Estimated Primary Completion Date: January 31, 2026
• Estimated Study Completion Date: January 31, 2028

Arms and Interventions

Arm	Intervention/treatment
Experimental: Phase 1 ASP0739 Monotherapy Dose Escalation; Participants with R/R solid tumors known to express NY-ESO-1 will receive ASP0739 on day 1 of each 28-day cycle for up to 6 doses, to determine the Recommended Phase 2 Dose (RP2D).	Drug: ASP0739; Intravenous (IV)
Experimental: Phase 2 ASP0739 + Pembrolizumab Safety Lead-in; Participants with R/R SS, MRCL or ovarian cancer will receive RP2D of ASP0739 on day 1 of each 28-day cycle for up to 6 doses in combination with pembrolizumab on Cycle 1 Day 1, and then every 6 weeks up to 4 doses during the treatment period to determine the RP2D of ASP0739 with pembrolizumab. A total of 17 doses of pembrolizumab may be available for qualifying participants.	Drug: ASP0739; Intravenous (IV); Drug: Pembrolizumab; Intravenous (IV)
Experimental: Phase 2 ASP0739 Monotherapy Dose Expansion; Participants with R/R SS, MRCL, or ovarian cancer and other solid tumors known to express NY-ESO-1 (melanoma, NSCLC-adenocarcinoma, squamous cell, and ESCC) will receive RP2D of ASP0739 on day 1 of each 28-day cycle for up to 6 doses.	Drug: ASP0739; Intravenous (IV)
Experimental: Phase 2 ASP0739 + Pembrolizumab Dose Expansion; Participants with R/R SS, MRCL, or ovarian cancer will receive RP2D of ASP0739 with pembrolizumab on day 1 of each 28-day cycle for up to 6 doses, in combination with 4 doses of pembrolizumab administered on cycle 1 day 1, and then every 6 weeks during the treatment period. A total of 17 doses of pembrolizumab may be available for qualifying participants.	Drug: ASP0739; Intravenous (IV); Drug: Pembrolizumab; Intravenous (IV)

Outcome Measures

Primary Outcome Measures :

1. Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 Single Agent [ Time Frame: 28 days ]

   A DLT is defined as any of the following occurring within 28 days of the first dose on cycle 1 day 1 (C1D1) considered related to IP.

   Grade (Gr) ≥ 2 autoimmune reaction; Gr 3 immune-related adverse events (irAEs) not resolving to Gr ≤ 1 in 3-5 days; Gr 4 irAEs; Gr ≥ 3 non-hematological AEs not resolving to Gr ≤ 2 within 72 hours of onset; Gr 4 neutropenia; Gr 3 febrile neutropenia; Gr 4 thrombocytopenia; Gr 3 anemia/thrombocytopenia with transfusion; Gr 4 anemia; aspartate aminotransferase (AST)/alanine aminotransferase (ALT) > 5 x upper limit of normal (ULN) (Gr ≥ 3) without liver metastases; AST/ALT > 8 x ULN with liver metastases; Confirmed Hy's Law; Gr ≥ 3 liver function test (LFT) abnormality; Gr 5 toxicity; > 2 week delay in cycle 2 due to treatment-related toxicity.

2. Incidence of Dose Limiting Toxicities (DLTs) for ASP0739 + Pembrolizumab Safety Lead-in [ Time Frame: 28 days ]

   A DLT is defined as any of the following occurring within 28 days of the first dose on C1D1 considered related to IP.

   Gr ≥ 2 autoimmune reaction; Gr 3 irAEs not resolving to Gr ≤ 1 in 3-5 days; Gr 4 irAEs; Gr ≥ 3 non-hematological AEs not resolving to Gr ≤ 2 within 72 hours of onset; Gr 4 neutropenia; Gr 3 febrile neutropenia; Gr 4 thrombocytopenia; Gr 3 anemia/thrombocytopenia with transfusion; Gr 3 thrombocytopenia with hospitalization; Gr 4 anemia; AST/ALT > 5 x ULN (Gr ≥ 3) without liver metastases; AST/ALT > 8 x ULN with liver metastases; Confirmed Hy's Law; Total Bilirubin > 3 x ULN (Gr ≥ 3); Gr ≥ 3 LFT abnormality; Gr 5 toxicity; > 2 week delay in cycle 2 due to treatment-related toxicity; Gr ≥ 2 pneumonitis; Gr ≥ 2 encephalopathy, meningitis, motor/sensory neuropathy; Guillain-Barre syndrome/myasthenic syndrome/myasthenia gravis; Infusion-related reaction requiring infusion discontinuation.

3. Number of Participants with adverse events (AEs) [ Time Frame: Up to 27 months ]
   An AE is any untoward medical occurrence in a participant temporally associated with the use of study IP, whether or not considered related to the study IP, and other study treatments. 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 study IP and other study treatments. This includes events related to the comparator and events related to the (study) procedures. AEs will be graded using NCI-CTCAE version 5.0.
4. Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 27 months ]
   An AE is considered "serious" if the event results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; results in congenital anomaly/birth defect; other medically important events.
5. Number of participants with laboratory value abnormalities and/or AEs [ Time Frame: Up to 27 months ]
   Number of participants with potentially clinically significant laboratory values.
6. Number of participants with 12-lead electrocardiogram (ECG) abnormalities and/or AEs [ Time Frame: Up to 27 months ]
   Number of participants with potentially clinically significant 12-lead ECG values.
7. Number of participants with vital sign abnormalities and/or AEs [ Time Frame: Up to 27 months ]
   Number of participants with potentially clinically significant vital sign values.
8. Number of participants with physical exam abnormalities and/or AEs [ Time Frame: Up to 27 months ]
   Number of participants with potentially clinically significant physical exam values.
9. Number of participants at each grade of the Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 27 months ]
   The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
10. Objective Response Rate per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review [ Time Frame: Up to 36 months ]
    iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed Complete Response (iCR) or Partial Response (iPR) per iRECIST by Independent Central Review.

Secondary Outcome Measures :

1. Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 36 months ]
   ORR is defined as the proportion of participants for each dose level whose best overall response is rated as Complete Response (CR) or Partial Response (PR) per RECIST v1.1.
2. Disease Control Rate per iRECIST (iDCR) [ Time Frame: Up to 36 months ]
   iDCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR, iPR or stable disease (SD), per iRECIST.
3. Disease Control Rate per RECIST v1.1 (DCR) [ Time Frame: Up to 36 months ]
   DCR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed CR, PR or stable disease (SD), per RECIST v1.1.
4. Progression-Free Survival per iRECIST (iPFS) by Independent Central Review [ Time Frame: Up to 36 months ]
   iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST, whichever comes first, as assessed by Independent Central Review.
5. iPFS per iRECIST by local assessment [ Time Frame: Up to 36 months ]
   iPFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per iRECIST, whichever comes first, as assessed by local assessment.
6. Progression-Free Survival per RECIST v1.1 (PFS) by Independent Central Review [ Time Frame: Up to 36 months ]
   PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1, whichever comes first, as assessed by independent central review.
7. PFS per RECIST v1.1 by local assessment [ Time Frame: Up to 36 months ]
   PFS is defined as the time from the start of the study treatment until death from any cause or radiographic disease progression assessed per RECIST v1.1, whichever comes first, as assessed by local assessment.
8. Duration of Overall Survival (OS) [ Time Frame: Up to 48 months ]
   OS is defined as the time from the date of first dose until the date of death from any cause.
9. Duration of Response per iRECIST (iDOR) by Independent Central Review [ Time Frame: Up to 36 months ]
   iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST, as assessed by Independent Central Review.
10. iDOR per iRECIST by local assessment [ Time Frame: Up to 36 months ]
    iDOR will be calculated only for the subgroup of participants with confirmed response iCR/iPR per iRECIST, as assessed by local assessment.
11. Duration of Response per RECIST (DOR) v1.1 by Independent Central Review [ Time Frame: Up to 36 months ]
    DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1, as assessed by Independent Central Review.
12. DOR per RECIST v1.1 by local assessment [ Time Frame: Up to 36 months ]
    DOR will be calculated only for the subgroup of participants with confirmed response CR/PR per RECIST v1.1, as assessed by local assessment.
13. ORR per iRECIST (iORR) by local assessment [ Time Frame: Up to 36 months ]
    iORR is defined as the proportion of participants for each dose level whose best overall response is rated as confirmed iCR or iPR, by local assessment.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Phase 1 Dose Escalation only:

- Participant has relapsed/refractory (R/R) solid tumor known to express NY-ESO-1 after completing available Standard of Care (SOC) therapy or is not a candidate for SOC therapy. NY-ESO-1 expression status is not required for participant entry.

Safety Lead-in, Phase 2 Single agent and Combination Therapy only:

• Participant has relapsed/refractory (R/R) synovial sarcoma (SS) or myxoid/round cell liposarcoma (MRCL) disease after undergoing available SOC treatment or is not a candidate for SOC therapy (must have previously received either an anthracycline or ifosfamide containing regimen or another systemic regimen, if not a candidate for either agent).

  • Participant has not received prior checkpoint inhibitor therapy (i.e., Programmed Cell Death Protein 1 [PD-1]/Programmed Death Ligand 1 [PD-L1] treatment naive)
  • SS: confirmation by the presence of a translocation between SYT on the X chromosome and SSX1, SSX2, or SSX4 on chromosome 18 (may be presented in the pathology report as t [X;18]).
  • MRCL: confirmation by the presence of the reciprocal chromosomal translocation t (12;16) (q13;p11) or t(12;22)(q13;q12).

• Participant has R/R ovarian cancer that is:

  • platinum resistant OR platinum-sensitive, but the participant is not a candidate for platinum or other SOC therapy.
  • Participant has not received prior checkpoint inhibitor therapy (i.e., naive PD-1/PD-L1 treatment participants).
• Participant has R/R solid tumor (melanoma, non-small cell lung cancer [NSCLC]-adenocarcinoma and squamous cell, or esophageal squamous cell carcinoma [ESCC]) after available SOC treatment or is not a candidate for SOC therapy (single-agent only).
• Participant consents to provide an archival tumor specimen in a tissue block or unstained serial slides prior to IP administration.
• Participant in phase 2 consents to provide tumor specimen obtained within 56 days prior to first dose of study treatment, as tissue block or unstained serial slides.
• Participant in phase 2 consents to undergoing a tumor biopsy (core needle biopsy or excision) during the treatment period.
• Participant has an Eastern Cooperative Oncology Group (ECOG) performance status of <= 2.
• Participant with life expectancy of >= 12 weeks at the time of screening.
• Participant must meet criteria for clinical laboratory tests during screening period.

• A female participant is eligible to participate if she is not pregnant and at least one of the following conditions apply:

  • Not a woman of childbearing potential (WOCBP) OR
  • WOCBP who agrees to follow the contraceptive guidance throughout the treatment period and for at least 6 months after the final investigational product (IP) administration.
• Female participant must not be breastfeeding at screening or during the study period and for 6 months after the final IP administration.
• Female participant must not donate ova at screening and throughout the study period and for 6 months after the final IP administration.
• A male participant with female partner(s) of childbearing potential must agree to use contraception during the treatment period and for at least 6 months after the final IP administration.
• Male participant must not donate sperm starting at screening and throughout the study period and for 6 months after the final IP administration.
• Participant agrees not to participate in another interventional study while on treatment.
• Participant measurable disease according to RECIST 1.1. For participant with only 1 measurable lesion and prior radiotherapy, the lesion must be outside the field of prior radiotherapy or must have documented progression following radiation therapy.

Exclusion Criteria:

• Participant has persistent non-hematological toxicities of >= grade 2 (National Cancer Institute's Common Terminology Criteria for Adverse Events [NCI-CTCAE] version 5.0), with symptoms and objective findings from treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation or surgery).

• Participant has received any of the following therapies (for inclusion in the study, all abnormalities must have returned to <= grade 1):

  • Systemic immunomodulators (checkpoint inhibitors)-except the dose escalation phase and the NY-ESO-1 solid tumor (melanoma, NSCLC-adenocarcinoma and squamous cell and ESCC) cohorts in the dose expansion phase of monotherapy, which may have received prior checkpoint inhibitor therapy
  • Immunosuppressive drugs including steroids <= 14 days prior to treatment
  • Cytotoxic agents <= 14 days prior to treatment
  • Investigational agent <= 21 days prior to treatment or 5 half-lives, whichever is shorter
  • Radiation therapy <= 21 days prior to treatment
• Participant has clinically active or untreated nervous system metastases. Participants with previously treated Central Nervous System (CNS) metastases are eligible, if they are 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.
• Participant has an active autoimmune disease. Participant 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.
• Participant was discontinued from prior immunomodulatory therapy due to a grade >= 3 toxicity that was mechanistically related (e.g., immune related) to the agent.
• Participant has known history of serious hypersensitivity reaction to a known ingredient of ASP0739 or pembrolizumab or severe hypersensitivity reaction to treatment with another monoclonal antibody.
• Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years prior to screening visit, except for locally curable malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast.
• Participant has received a prior allogeneic bone marrow or solid organ transplant.
• Participant has an active uncontrolled infection within 14 days of treatment.
• Participant is known to have human immunodeficiency virus infection.
• Participant has active hepatitis B or C or other active hepatic disorder or participant is on hepatitis treatment. Hepatitis C RNA testing is not required in participants with negative hepatitis C antibody testing.
• Participant has any condition which makes the participant unsuitable for study participation.
• Participant has had a major surgical procedure and has not completely recovered within 28 days prior to the start of study treatment.
• Participant 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.
• Participant is expected to require another form of anti-cancer therapy while on study treatment.
• Participant has a known or suspected hypersensitivity to bovine-derived protein or has suspected hypersensitivity to any ingredients of ASP0739.

Additional Exclusion Criteria for Participants in Combination Therapy Cohorts

• Participants with a history of myocarditis or congestive heart failure (as defined by New York Heart Associated Functional Classification III or IV), as well as unstable angina, serious uncontrolled cardiac arrhythmia, uncontrolled infection, or myocardial infarction 6 months prior to study entry.
• Participants with active interstitial lung disease (ILD)/pneumonitis or a history of ILD/pneumonitis requiring treatment with systemic steroids.
• Participants with baseline pulse oximetry < 92% "on Room air."
• Participants must not have known microsatellite instability-high or deficient MisMatch Repair.

Contacts and Locations

Locations

United States, California

City of Hope

Duarte, California, United States, 91010

United States, Florida

University of Miami

Miami, Florida, United States, 33136

United States, Illinois

Northwestern University Robert H. Lurie Comprehensive Cancer Center

Chicago, Illinois, United States, 60611

The University of Chicago Medicine

Chicago, Illinois, United States, 60637

United States, New York

NYU Perlmutter Cancer Center

New York, New York, United States, 10016

United States, Oregon

Oregon Health & Science University

Portland, Oregon, United States, 97239

United States, Rhode Island

Brown University

Providence, Rhode Island, United States, 02903

Sponsors and Collaborators

Astellas Pharma Global Development, Inc.

Investigators

• Study Director: Medical Director; Astellas Pharma Global Development, Inc.

More Information

• Responsible Party: Astellas Pharma Global Development, Inc.
• ClinicalTrials.gov Identifier: NCT04939701
• Other Study ID Numbers: 0739-CL-0101
• First Posted: June 25, 2021
• Last Update Posted: January 25, 2023
• Last Verified: January 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: 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.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (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.
• URL: https://www.clinicalstudydatarequest.com/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):

NY-ESO-1; ASP0739; Solid Tumor; NSCLC; ESCC; MRCL; Ovarian Cancer; R/R SS

Additional relevant MeSH terms:

Ovarian Neoplasms; Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Ovarian Diseases; Adnexal Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Endocrine System Diseases; Gonadal Disorders; Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents