What side effects are associated with this type of intervention?

Common side effects of treatments that reactivate T-cells to attack tumors, such as immune checkpoint inhibitors like pembrolizumab, include immune-related adverse events. These can manifest as colitis, pneumonitis, hepatitis, endocrinopathies (e.g., thyroiditis, adrenal insufficiency), and skin reactions like rash and pruritus. Severe side effects can include high-grade pneumonitis and hepatitis, requiring prompt management with immunosuppressive therapies.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of solid tumors, focusing on reactivating T-cells to attack tumors. Pembrolizumab (Keytruda) targets PD-1 and is approved for various cancers, including melanoma, non-small cell lung cancer (NSCLC), and others. Nivolumab (Opdivo), another PD-1 inhibitor, and ipilimumab (Yervoy), which targets CTLA-4, are also approved for similar indications. These treatments work by blocking inhibitory signals to T-cells, thereby enhancing the immune system's ability to target and destroy cancer cells, similar to the investigational drug ASP1570.

What other types of research exist?

Promising alternatives to ASP1570 for reactivating T-cells in solid tumor patients include: 1) Nivolumab-relatlimab, which has shown efficacy in metastatic melanoma by targeting PD-1 and LAG-3 pathways. 2) Anti-CD20 monoclonal antibodies combined with IL-15 superagonist ALT-803, enhancing NK cell responses and antibody-dependent cellular cytotoxicity. 3) ONC201, a DRD2 antagonist, which has demonstrated potential in treating gliomas by targeting mitochondrial protease ClpP. These therapies represent novel approaches in immunotherapy for solid tumors.

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ASP1570 + Pembrolizumab for Advanced Cancer

Phase 1 & 2

Recruiting

Research Sponsored by Astellas Pharma Global Development, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Participant's adverse events from prior therapy have improved to grade 1 or baseline at least 14 days prior to the first dose of IP

Participant has no actionable driver mutation (e.g., EGFR, ALK, NTRK) for NSCLC monotherapy expansion cohort

Must not have

Participant has a history of bleeding diathesis

Participant has known or suspected hypersensitivity to ASP1570 or pembrolizumab

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 27 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing ASP1570, a new drug that helps the immune system fight cancer by reactivating T-cells. It targets adults with advanced solid tumors that have spread and are not responding to standard treatments. ASP1570 works by counteracting the signals that tumors use to turn off T-cells. The study will determine the best dose and test its effectiveness alone or with another drug called pembrolizumab.

Who is the study for?

Adults with advanced solid tumors, including NSCLC or melanoma, who have worsened after standard therapy or can't receive it. They must have at least one measurable tumor lesion and be in good physical condition (ECOG 0-1). Participants should not have had recent major surgery, known allergies to the drugs being tested, uncontrolled illnesses, certain infections like HIV/HBV/HCV, or received other treatments that could interfere with the trial.

What is being tested?

The study tests ASP1570 alone or combined with pembrolizumab on adults with advanced solid tumors. Part 1 determines the best dose of ASP1570; participants take increasing doses unless significant issues arise. In Part 2, they continue with the established best dose from Part 1. Pembrolizumab is given every six weeks for some patients.

What are the potential side effects?

Potential side effects include immune-related reactions due to T-cell activation (like inflammation in various organs), infusion reactions from pembrolizumab administration, fatigue, possible digestive disturbances and changes in blood counts which may increase infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My side effects from previous treatments have mostly gone away.

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My lung cancer does not have mutations like EGFR, ALK, or NTRK.

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My condition worsened after standard treatments, or I can't or won't use them.

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My cancer (NSCLC or melanoma) diagnosis is confirmed by lab tests.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My NSCLC worsened after first-line checkpoint inhibitor therapy.

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My organs are functioning well enough for treatment, based on recent tests.

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My cancer is advanced and cannot be removed by surgery.

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My lung cancer is stage IV, PD-L1 positive, and lacks specific gene changes.

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I am not pregnant and follow the required birth control measures.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have a history of unusual bleeding.

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I am allergic to ASP1570 or pembrolizumab.

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I had radiotherapy less than 2 weeks ago or have had radiation pneumonitis.

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I have not taken medication for an infection in the last 14 days.

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I have had a stem cell or organ transplant.

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I will need additional cancer treatment while on this study.

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I have symptoms from cancer spread to my brain or it's unstable.

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I need to take strong or moderate drugs that affect liver enzyme CYP2D6 during the study.

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I have had or currently have pneumonitis that needed strong steroids.

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I haven't taken any experimental drugs within the last 21 days or before the half-life period prior to starting ASP1570 or pembrolizumab.

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I am HIV-positive and have had Kaposi sarcoma or Multicentric Castleman Disease.

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I have not had any cancer except for certain types in the last 2 years.

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I stopped my previous immune therapy due to severe side effects.

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I need blood-thinning medication.

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My high blood pressure is not well-controlled.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 27 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 27 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 27 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Change from baseline to 45 days after End of Treatment (EOT) in laboratory values

Incidence of Dose Limiting Toxicities (DLTs) for ASP1570 Single Agent

Number of Participants with Adverse Events (AEs)

+2 more

Secondary study objectives

Changes in tumor infiltration with CD4/CD8 cells

Disease Control Rate (DCR) of ASP1570 per RECIST 1.1

Disease Control Rate (DCR) of ASP1570 per iRECIST

+9 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

10Treatment groups

Experimental Treatment

Group I: ASP1570 Monotherapy Tumor Specific Dose Expansion - Response-triggered Tumor (Part 2)Experimental Treatment1 Intervention

Participants will receive ASP1570 in a 21-day cycle in tumor-specific cohort if dose escalation cohort had partial response (PR) or complete response (CR) in same tumor type at a dose that has been cleared and deemed tolerable.

Group II: ASP1570 Monotherapy Dose Expansion - Stepwise dosing (Part 2)Experimental Treatment1 Intervention

Participants will receive ASP1570 administered by intra-subject dose escalation with gradual multiple dose steps (e.g., 3 steps) and increased dose up to RP2D in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group III: ASP1570 Monotherapy Dose Expansion - Prophylactic Steriods (Part 2)Experimental Treatment1 Intervention

Participants will receive RP2D of ASP1570 along with the prophylactic steroids in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group IV: ASP1570 Monotherapy Dose Expansion - Non-Small Cell Lung Carcinoma (NSCLC) (Part 2)Experimental Treatment1 Intervention

Participants who have NSCLC will receive RP2D of ASP1570 daily in a 21-day cycle.

Group V: ASP1570 Monotherapy Dose Expansion - Melanoma (Part 2)Experimental Treatment1 Intervention

Participants who have melanoma will receive recommended Phase 2 dose (RP2D) of ASP1570 in a 21-day cycle.

Group VI: ASP1570 Monotherapy Dose Expansion - Intermittent dosing (Part 2)Experimental Treatment1 Intervention

Participants will receive RP2D of ASP1570 with some periodical drug holiday in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group VII: ASP1570 Monotherapy Dose Expansion - Food Effect (Part 2)Experimental Treatment1 Intervention

Participants will receive RP2D of ASP1570 after the meal in a 21-day cycle. This cohort will be opened at the discretion of the sponsor.

Group VIII: ASP1570 Monotherapy Dose Escalation (Part 1)Experimental Treatment1 Intervention

Participants will receive daily dose of ASP1570 in a 21-day cycle.

Group IX: ASP1570 + pembrolizumab Combination therapy Dose Expansion - NSCLC (Part 2)Experimental Treatment2 Interventions

Participants who have NSCLC will receive RP2D of ASP1570 daily in a 21-day cycle. pembrolizumab will be administered every 6 weeks on day 1 of every other ASP1570 cycle.

Group X: ASP1570 + pembrolizumab Combination therapy Dose Escalation (Part 1)Experimental Treatment2 Interventions

Participants will receive daily dose of ASP1570 in a 21-day cycle. pembrolizumab will be administered every 6 weeks on day 1 of every other ASP1570 cycle.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

pembrolizumab

2017

Completed Phase 3

~5890

0 / 25Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Immune therapies for solid tumors, such as those involving ASP1570, work by reactivating T-cells to target and attack cancer cells. Tumors often evade the immune system by sending 'off' signals to T-cells, rendering them inactive. Treatments like ASP1570 aim to switch these T-cells back on, enabling them to recognize and destroy tumor cells. This approach is crucial for patients with solid tumors, especially those with advanced or metastatic cancer, as it offers a potential new avenue for treatment when standard therapies have failed or are not an option.