A Phase 1b/2 Study of ASP2998 as Monotherapy and in Combination With Standard Therapies in Participants With Locally Advanced Unresectable or Metastatic Solid Tumors

Plain English Summary

A Study of ASP2998 Given by Itself and Given With Standard Therapies in People With Solid Tumors is a Phase 2 clinical trial sponsored by Astellas Pharma Global Development, Inc. studying Locally Advanced or Metastatic Malignant Solid Tumors. This trial tests a new drug called ASP2998, alone or with standard treatments, for advanced solid tumors. It is for adults with specific types of solid tumors that have spread or cannot be removed by surgery, and have not responded to or cannot tolerate other treatments. Participation involves receiving ASP2998 by IV infusion, either by itself or with other cancer drugs, and attending regular study visits for monitoring. Alternative treatments include other standard chemotherapy, targeted therapies, or immunotherapy, depending on the cancer type and prior treatments. The trial aims to enroll 428 participants.

Official 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 medi

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with locally advanced, unresectable, or metastatic solid tumors are eligible. Specific cancer types include urothelial carcinoma, non-small cell lung cancer (NSCLC), gastric cancer, gastroesophageal junction cancer, and certain HER2-negative breast cancers. Patients must have progressed on or be unable to receive standard therapies, with specific criteria for prior treatments depending on the treatment arm. Individuals with cancer that has spread to the brain or spinal cord lining (leptomeningeal disease) or with active brain metastases are generally not eligible. This trial is studying Locally Advanced or Metastatic Malignant Solid Tumors, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure the safety and tolerability of ASP2998, meaning how often side effects occur and how well patients can handle the treatment, which is crucial for determining its potential The specific primary outcome measures are: Number of Participants with Dose Limiting Toxicities (DLTs) (Up to 21 days); Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (Up to 21 Months); Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to 21 months); Number of participants with vital sign abnormalities and/or AEs (Up to 19 months); Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Up to 19 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial is important because it investigates a novel drug, ASP2998, targeting the TROP2 protein, to address the unmet need for effective treatments in patients with advanced solid tumors that have Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Locally Advanced or Metastatic Malignant Solid Tumors, where improved treatment options are needed.

Investor Insight

This Phase 1b/2 study represents an early-stage investment in a novel oncology drug targeting TROP2, a marker present in various solid tumors, with potential to enter a competitive market if successfu Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific type of ASP2998 treatment you might receive (alone or with other drugs) and what side effects are most common. Be prepared for regular clinic visits for drug infusions, blood tests, scans, and to report any new symptoms or side effects. Understand that this is an early study, and while it aims to find effective treatments, the primary focus is on safety and determining the right dose. This trial is currently recruiting participants. The trial is being conducted at 6 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 428 participants

Interventions

• DRUG: ASP2998 — Intravenous infusion
• DRUG: Pembrolizumab — Intravenous infusion
• DRUG: Enfortumab Vedotin — Intravenous infusion
• DRUG: Carboplatin — Intravenous infusion

Primary Outcomes

• Number of Participants with Dose Limiting Toxicities (DLTs) (Up to 21 days)
• Number of Participants with Treatment-Emergent Adverse Events (TEAEs) (Up to 21 Months)
• Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to 21 months)
• Number of participants with vital sign abnormalities and/or AEs (Up to 19 months)
• Number of participants with electrocardiogram (ECG) abnormalities and/or AEs (Up to 19 months)

Secondary Outcomes

• 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)

Full Eligibility Criteria

Inclusion Criteria:

* 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, 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.
  * Participant is also eligible if there is disease progression within 12 months of receiving adjuvant or neoadjuvant 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 ASP2998 combination therapy (including the tumor-specific backfill participants from the combination therapy dose escalation), the following criteria apply for the NSCLC first line (1L) ASP2998 + Pembrolizumab + Carboplatin Dose Escalation and Expansion Cohort(s):

  * Participant has locally advanced unresectable or metastatic NSCLC (adenocarcinoma only, no mixed histology allowed), with known PD-L1 status, without AGA, according to local testing.
  * Participant is also eligible if there is disease progression \> 12 months after completing adjuvant or neoadjuvant therapy for resectable disease.
  * Participant has not received prior therapy for metastatic disease.
  * No prior exposure to TROP2, STING agonist or TopI directed therapy is allowed in dose escalation or dose expansion.
* For ASP2998 combination therapy (including the tumor-specific backfill participants from the combination therapy dose escalation), the following criteria apply for the Urothelial Carcinoma 1L ASP2998 + Pembrolizumab + Enfortumab Vedotin Dose Escalation and Expansion Cohort(s):

  * 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. Participant with urothelial carcinoma (transitional cell) with \< 50% squamous differentiation or mixed cell types is eligible.
  * Participant is also eligible if there is disease progression \> 12 months after completing adjuvant or neoadjuvant therapy for resectable disease.
  * Participant has not received prior therapy for metastatic disease.
  * No prior exposure to TROP2, STING agonist or TopI directed therapy is allowed in dose escalation or dose expansion.
* For ASP2998 combination therapy (including the tumor-specific backfill participants from the combination therapy dose escalation), the following criteria apply for the NSCLC 2L+ ASP2998 + Pembrolizumab Dose 

Trial Locations

• John Theurer Cancer Center at Hackensack University Medical Center, Hackensack, New Jersey, United States
• START New York Long Island, New Hyde Park, New York, United States
• Tennessee Oncology, Nashville, Tennessee, United States
• NEXT Virginia, Fairfax, Virginia, United States
• National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
• The Cancer Institute Hospital of JFCR, Koto-ku, Tokyo, Japan

Frequently Asked Questions

Related Conditions

• Urothelial Carcinoma
• Non-Small Cell Lung Cancer (NSCLC)
• Gastric Cancer
• Gastroesophageal Junction (GEJ) Cancer
• Breast Cancer
• Solid Tumors
• Metastatic Cancer
• Advanced Cancer
• Oncology
• Cancer Immunotherapy

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