Clinical trial NCT04939701: Study of ASP0739 Alone and With Pembrolizumab in Advanced Solid Tumors With NY-ESO-1 Expression Participants
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Ovarian Cancer
NSCLC
ESCC
Solid Tumors
Keywords: NY-ESO-1
ASP0739
Solid Tumor
NSCLC
ESCC
MRCL
Ovarian Cancer
R/R SS
Lead sponsor: Astellas Pharma Inc
Sponsor class: INDUSTRY
First posted: 2021-06-25
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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

This study also evaluated 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.

Detailed description: The study comprised of 2 phases. Phase 1 (dose escalation) included 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) included participants with relapsed/refractory Synovial Sarcoma (SS), myxoid/round cell liposarcoma (MRCL), and ovarian cancer who had not responded to Standard of Care (SOC) or were ineligible for standard therapy. Phase 2 single agent also included 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 were only enrolled into the monotherapy arm of the dose expansion cohort.

Eligibility 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.

Primary outcomes:
measure: Number of Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 Day 1 (C1D1) up to C1D28
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) & Serious Adverse Events (SAEs)
timeFrame: From first dose up to 198 days
measure: Number of Participants With ECOG Performance Status at C1D2
timeFrame: At C1D2
measure: Number of Participants With ECOG Performance Status at C1D8
timeFrame: At C1D8
measure: Number of Participants With ECOG Performance Status at CID15
timeFrame: At CID15
measure: Number of Participants With ECOG Performance Status at CID22
timeFrame: At CID22
measure: Number of Participants With ECOG Performance Status at C2D1
timeFrame: At C2D1
measure: Number of Participants With ECOG Performance Status at C2D2
timeFrame: At C2D2
measure: Number of Participants With ECOG Performance Status at C2D8
timeFrame: At C2D8
measure: Number of Participants With ECOG Performance Status at C2D15
timeFrame: At C2D15
measure: Number of Participants With ECOG Performance Status at C2D22
timeFrame: At C2D22
measure: Number of Participants With ECOG Performance Status at C3D1
timeFrame: At C3D1
measure: Number of Participants With ECOG Performance Status at C3D8
timeFrame: At C3D8
measure: Number of Participants With ECOG Performance Status at C3D15
timeFrame: At C3D15
measure: Number of Participants With ECOG Performance Status at C3D22
timeFrame: At C3D22
measure: Number of Participants With ECOG Performance Status at C4D1
timeFrame: At C4D1
measure: Number of Participants With ECOG Performance Status at C4D8
timeFrame: At C4D8
measure: Number of Participants With ECOG Performance Status at C4D15
timeFrame: At C4D15
measure: Number of Participants With ECOG Performance Status at C4D22
timeFrame: At C4D22
measure: Number of Participants With ECOG Performance Status at C5D1
timeFrame: At C5D1
measure: Number of Participants With ECOG Performance Status at C5D15
timeFrame: At C5D15
measure: Number of Participants With ECOG Performance Status at C6D1
timeFrame: At C6D1
measure: Number of Participants With ECOG Performance Status at C6D15
timeFrame: At C6D15
measure: Number of Participants With ECOG Performance Status at End of Treatment (EOT) Visit
timeFrame: At EOT visit (day 175)
measure: Number of Participants With ECOG Performance Status at Safety Follow up 30 Days
timeFrame: At 30 days safety follow up (day 198)
measure: Number of Participants With ECOG Performance Status at Safety Follow up 60 Days
timeFrame: At 60 days safety follow up (day 228)
measure: Number of Participants With ECOG Performance Status at Safety Follow up 90 Days
timeFrame: At 90 days safety follow up (day 258)
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: C1D1 up to C1D28
measure: Objective Response Rate Per Immune Response Evaluation Criteria in Solid Tumors (iRECIST) (iORR) by Independent Central Review
timeFrame: From first dose up to 525 days
Secondary outcomes:
measure: Objective Response Rate Per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (ORR) by Investigator Assessment
timeFrame: From first dose up to 525 days
measure: Disease Control Rate Per iRECIST (iDCR) by Investigator Assessment
timeFrame: From first dose up to 525 days
measure: Disease Control Rate Per RECIST v1.1 (DCR) by Investigator Assessment
timeFrame: From first dose up to 525 days
measure: Progression-Free Survival Per iRECIST (iPFS) by Independent Central Review
timeFrame: From first dose up to 525 days
measure: iPFS Per iRECIST by Investigator Assessment
timeFrame: From first dose up to 525 days
measure: Progression-Free Survival Per RECIST v1.1 (PFS) by Investigator Assessment
timeFrame: From first dose up to 525 days
measure: Duration of Overall Survival (OS)
timeFrame: From first dose up to 525 days
measure: Duration of Response Per iRECIST (iDOR)
timeFrame: From first response up to 525 days
measure: Duration of Response Per RECIST (DOR) v1.1
timeFrame: From first response up to 525 days
measure: ORR Per iRECIST (iORR) by Investigator Assessment
timeFrame: From first dose up to 525 days
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Chicago
country: United States
facility: Northwestern University Robert H. Lurie Comprehensive Cancer Center
state: Illinois
city: Chicago
country: United States
facility: The University of Chicago Medicine
state: Illinois
city: New York
country: United States
facility: NYU Perlmutter Cancer Center
state: New York
city: Providence
country: United States
facility: Brown University
state: Rhode Island
Study officials:
affiliation: Astellas Pharma Global Development, Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: