A Study of ASP2998 Given by Itself and Given With Standard Therapies in People With Solid Tumors

NCT07287995 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2998-CL-01012025-524567-21
• Study Type: interventional
• Target: 428
• Locations: 2 countries
• Sites: 7

Brief Summary

Specific proteins found in tumors help the tumors spread and grow. People with solid tumors often have a protein called TROP2 in their tumor. ASP2998 is being developed to attach to TROP2 and then attack the tumor cells in people with solid tumors. ASP2998 will either be given by itself, or given together with one or more of standard cancer treatments pembrolizumab, carboplatin, and enfortumab vedotin. This is an early development study to collect information about ASP2998 in people with solid tumors. In this study ASP2998 will be given to humans for the first time. Early development studies are mostly about safety, but also to find the most suitable dose. Other aims are to check if ASP2998 shows signs of reducing tumor growth, to learn how the body processes ASP2998, and to check if there are changes either in the TROP2 protein or in the immune system. The main aim of the study is to check the safety of ASP2998 when given by itself and given with the standard cancer treatments, and how well it is tolerated. People in this study will be adults with locally advanced, unresectable or metastatic solid tumors. Locally advanced means the cancer has spread to nearby tissue. Unresectable means the cancer cannot be removed by surgery. Metastatic means the cancer has spread to other parts of the body. People's cancer came back or became worse after previous treatment or they couldn't receive treatment. Some people who had previously refused treatment may be able to take part. This will depend on which study treatment they receive. People will either have cancer in the bladder lining (urothelial cancer), non-small cell lung cancer (NSCLC), gastric cancer or cancer where the food pipe joins the stomach (gastroesophageal cancer, or GEJ), or certain types of breast cancer. People cannot take part if the cancer cells have spread to the thin tissue covering the brain and spinal cord (leptomeningeal disease), have symptoms of cancer in the brain or nervous system, or need medicines to suppress their immune system. In this study, ASP2998 will be given to humans for the first time. ASP2998 will either be given by itself, or given together with one or more of standard cancer treatments pembrolizumab, carboplatin and enfortumab vedotin. The standard cancer treatment given will depend on which cancer people have. The study will have 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP2998 given by itself or together with one or more of the standard cancer treatments. Any medical problems will be recorded for each dose. This is done to find suitable doses of ASP2998 to use in Part 2. In Part 2, other different small groups will receive suitable doses of ASP2998 worked out from Part 1. ASP2998 will either be given by itself or given together with one or more of the standard cancer treatments. This part will also check how each type of cancer responds to ASP2998 when given by itself or together with the standard cancer treatments. In both parts of the study, safety checks will be done at each visit, and the doctors will continue to check for medical problems throughout the study. ASP2998 will be given slowly through a tube into a vein (infusion). People will continue to receive ASP2998 until their cancer gets worse, they can't tolerate ASP2998, they start other cancer treatment, they or the doctor decides the person should stop receiving ASP2998.

Conditions

Locally Advanced or Metastatic Malignant Solid Tumors

Keywords

ASP2998; Safety; Tolerability; Pembrolizumab; Enfortumab Vedotin; Carboplatin; Non-small cell lung cancer; Gastroesophageal junction cancer; Breast cancer; Pharmacokinetics; Urothelial carcinoma

Outcome Measures

Primary Outcomes (7)

• Number of Participants with Dose Limiting Toxicities (DLTs)

  A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1) that cannot clearly be attributed to a cause other than ASP2998 administered in monotherapy or in combination with standard treatments.

  Up to 21 days

• Number of Participants with Treatment-Emergent Adverse Events (TEAEs)

  An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. NOTE: 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 intervention. This includes events related to the comparator, if applicable, and events related to the (study) procedures. A TEAE is an AE with onset at any time from first dosing until last scheduled procedure.

  Up to 21 Months

• Number of participants with laboratory value abnormalities and/or adverse events (AEs)

  Number of participants with potentially clinically significant laboratory values.

  Up to 21 months

• Number of participants with vital sign abnormalities and/or AEs

  Number of participants with potentially clinically significant vital sign values.

  Up to 19 months

• Number of participants with electrocardiogram (ECG) abnormalities and/or AEs

  Number of participants with potentially clinically significant ECG values.

  Up to 19 months

• Number of Participants with Physical Examination (PE) abnormalities and/or AEs

  Number of participants with potentially clinically significant PE values.

  Up to 19 months

• Number of Participants at each grade of Eastern Cooperative Oncology Group (ECOG) performance status score

  The ECOG scale will be used to assess performance status. Scores range from 0 (fully active) to 5 (dead). Negative change scores represent an improvement. Positive scores represent a decline in performance.

  Up to 19 months

Secondary Outcomes (13)

• Objective Response Rate (ORR) of ASP2998 per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

  Up to 27 months

• Duration of Response (DOR) of ASP2998 per RECIST v1.1

  Up to 27 months

• Disease Control Rate (DCR) of ASP2998 per RECIST v1.1

  Up to 27 months

• Progression Free Survival (PFS) per RECIST v1.1

  Up to 27 months

• Overall Survival (OS)

  Up to 33 months

Study Arms (6)

ASP2998 Dose Escalation

EXPERIMENTAL

Participants with urothelial carcinoma (UC), NSCLC, gastric/GEJ cancer or breast cancer (HER2-negative) will receive sequential doses of ASP2998 in a 21-day cycle.

Drug: ASP2998

ASP2998 Dose Expansion

EXPERIMENTAL

Participants with UC or NSCLC will receive ASP2998 in a 21-day cycle with dose level(s) selected from dose escalation.

Drug: ASP2998

ASP2998 Monotherapy Dose Escalation (Tumor Specific)

EXPERIMENTAL

Participants with select tumor types will receive ASP2998 in a 21-day cycle at dose level(s) based on emerging data.

Drug: ASP2998

ASP2998 Monotherapy Dose Expansion (Tumor Specific)

EXPERIMENTAL

Participants with select tumor types will receive ASP2998 in a 21-day cycle at dose level(s) based on emerging data.

Drug: ASP2998

ASP2998 Combination Therapy Dose Escalation (Tumor Specific)

EXPERIMENTAL

Participants with select tumor types will receive ASP2998 in a 21-day cycle at dose level(s) based on emerging data.

Drug: ASP2998; Drug: Pembrolizumab; Drug: Enfortumab Vedotin; Drug: Carboplatin

ASP2998 Combination Therapy Dose Expansion (Tumor Specific)

EXPERIMENTAL

Participants with select tumor types will receive ASP2998 in a 21-day cycle at dose level(s) based on emerging data.

Drug: ASP2998; Drug: Pembrolizumab; Drug: Enfortumab Vedotin; Drug: Carboplatin

Interventions

ASP2998 DRUG

Intravenous infusion

ASP2998 Combination Therapy Dose Escalation (Tumor Specific); ASP2998 Combination Therapy Dose Expansion (Tumor Specific); ASP2998 Dose Escalation; ASP2998 Dose Expansion; ASP2998 Monotherapy Dose Escalation (Tumor Specific); ASP2998 Monotherapy Dose Expansion (Tumor Specific)

Pembrolizumab DRUG

Intravenous infusion

Also known as: Keytruda

ASP2998 Combination Therapy Dose Escalation (Tumor Specific); ASP2998 Combination Therapy Dose Expansion (Tumor Specific)

Enfortumab Vedotin DRUG

Intravenous infusion

Also known as: Padcev

ASP2998 Combination Therapy Dose Escalation (Tumor Specific); ASP2998 Combination Therapy Dose Expansion (Tumor Specific)

Carboplatin DRUG

Intravenous infusion

ASP2998 Combination Therapy Dose Escalation (Tumor Specific); ASP2998 Combination Therapy Dose Expansion (Tumor Specific)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For the ASP2998 monotherapy dose escalation (excluding urothelial and non-small cell lung cancer (NSCLC) tumor-specific backfill participants), the following criteria apply:
• Participant has a confirmed diagnosis of locally advanced unresectable or metastatic solid tumors.
• Participant has progressed on, is ineligible for, or has refused all available standard therapies (no limit to the number of prior treatment regimens).
• Prior exposure to TROP2, stimulator of interferon genes (STING) agonist or topoisomerase I (TopI) directed therapy is allowed.
• Participant must have one of the following malignancies: Urothelial carcinoma, NSCLC (nonsquamous cell histology), Gastric/ gastroesophageal junction (GEJ) cancer, Breast cancer (human epidermal growth factor receptor 2 \[HER2\]-negative; local testing for HER2 status is acceptable).
• For all tumor types, any component of neuroendocrine histology is ineligible.
• For the ASP2998 NSCLC second line (2L)+ Monotherapy Dose Expansion Cohort(s) (including the tumor-specific backfill participants from the monotherapy dose escalation), the following criteria apply:
• Participant has locally advanced unresectable or metastatic NSCLC with known programmed cell death-1 (PD-L1) status, without actionable oncogenic alteration (AGA), according to local testing.
• Participant must have histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic NSCLC that has progressed on or after receiving platinum-based chemotherapy and/or checkpoint inhibitors according to local/regional standard of care.
• Participant is also eligible if there is disease progression within 12 months of receiving neoadjuvant or adjuvant therapy for resectable disease.
• Participant must be eligible to receive treatment in 2L+ setting.
• Participant must have had no more than 3 prior lines of therapy.
• No prior exposure to TROP2, STING agonist or TopI directed therapy is allowed.
• For the ASP2998 Urothelial Carcinoma Monotherapy Dose Expansion Cohort(s) (including the tumor-specific backfill participants from the monotherapy dose escalation), the following criteria apply:
• Participant must have histologically or cytologically confirmed diagnosis of urothelial carcinoma (i.e., cancer of the bladder, renal pelvis, ureter or urethra) in locally advanced unresectable or metastatic setting that has progressed on a combination of enfortumab vedotin and pembrolizumab according to local/regional standard of care. Participant with urothelial carcinoma (transitional cell) with \< 50% squamous differentiation or mixed cell types is eligible.

You may not qualify if:

• Participant weighs \< 40 kg during screening.
• Participant has known active central nervous system (CNS) metastases. NOTE: A participant with CNS metastases that have been treated with surgery and/or radiation therapy, who is no longer taking pharmacologic doses of glucocorticoids and is neurologically stable, is eligible. Prophylactic use of anticonvulsants is permitted.
• Participant has any of the following:
• Any history of recurrent Grade 3 AEs/ immune-related AEs (irAEs) or history of Grade 4 irAEs related to prior anticancer therapy.
• Participant has active or prior autoimmune or inflammatory disorders requiring systemic anti-inflammatory or immunosuppressive therapy within the past 3 years. Participants with type 1 diabetes mellitus or endocrinopathies stably maintained on appropriate replacement therapy will not be excluded.
• Participant has uncontrolled diabetes mellitus. For cohorts receiving enfortumab vedotin, uncontrolled diabetes is defined as hemoglobin A1c (HbA1c) of ≥ 8% or HbA1c of 7% to \< 8% with associated diabetes symptoms (polyuria or polydipsia).
• Participant has leptomeningeal disease as a manifestation of the current malignancy.
• Participant has a known additional malignancy that requires active treatment, with the exception of any of the following:
• Locally curable malignancies that have been apparently cured with no recurrence in the past 2 years.
• Adequately treated stage I cancer from which the participant is currently in remission and has been in remission for ≥ 2 years.
• Any other cancer from which the participant has been disease-free for ≥ 5 years.
• Participant has a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of first administration of study intervention. Inhaled or topical steroids and adrenal replacement doses ≤ 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
• Participant has jaundice or known current active liver disease from any cause, including hepatitis A (hepatitis A virus (HAV) immunoglobulin M (IgM) positive, but testing for hepatitis A viral load in screening is not required), hepatitis B (hepatis B virus (HBV) (hepatitis B surface antigen positive, or HBV DNA positive if HBsAg is negative and anti-HBs and/or anti-HBc positive)), or hepatitis C (HCV antibody positive, confirmed by HCV RNA). NOTE: screening for these infections should be conducted per local requirements.
• Participant has a known history of human immunodeficiency virus (HIV) infection with acquired immunodeficiency syndrome (AIDS)-related complications. HIV testing will be conducted per local requirements.
• Participant has clinically significant cardiac disease, defined as any of the following:

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead

Study Sites (7)

John Theurer Cancer Center at Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

START New York Long Island

New Hyde Park, New York, 11042, United States

RECRUITING

Tennessee Oncology

Nashville, Tennessee, 37203, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, Japan

RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, Japan

RECRUITING

The Cancer Institute Hospital of JFCR

Koto-ku, Tokyo, Japan

RECRUITING

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Breast Neoplasms; Carcinoma, Transitional Cell

Interventions

pembrolizumab; enfortumab vedotin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals

Study Officials

• Medical Monitor

  Astellas Pharma Global Development, Inc.

  STUDY DIRECTOR

Central Study Contacts

Astellas Pharma Global Development, Inc.

CONTACT

800-888-7704; Astellas.registration@astellas.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2025
• First Posted: December 17, 2025
• Study Start: February 5, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2029
• Last Updated: June 10, 2026

Record last verified: 2026-06

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 (3); US (4)