What is the mechanism of action of this treatment?

Targeted therapies for solid tumors, such as ASP3082, work by inhibiting abnormal proteins produced by specific genetic mutations like the G12D mutation in the KRAS gene. This is crucial for patients because it directly disrupts the cancer's growth and survival pathways. Similar treatments include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, which target specific enzymes and growth factor receptors on cancer cells. These therapies offer a personalized approach, potentially improving outcomes and reducing side effects compared to traditional chemotherapy.

What side effects are associated with this type of intervention?

Common side effects of treatments for solid tumors, particularly those targeting KRAS mutations like ASP3082, include fatigue, diarrhea, skin rash, and liver toxicity. When combined with cetuximab or chemotherapy, additional side effects may include nausea, vomiting, decreased blood cell counts, and increased risk of infections. Monitoring is essential to manage these side effects effectively.

What prior FDA approvals exist?

FDA-approved treatments for solid tumors often target specific genetic mutations that drive cancer growth. For example, therapies targeting the KRAS gene mutations, such as cetuximab and panitumumab, are used in colorectal cancer with wild-type KRAS. Additionally, targeted therapies like vemurafenib and dabrafenib inhibit the BRAF V600E mutation in melanoma. While specific inhibitors for the KRAS G12D mutation are still under investigation, these examples illustrate the broader approach of targeting genetic mutations in solid tumors.

What other types of research exist?

Promising alternatives to ASP3082 for solid tumors with KRAS mutations include AZ304, a dual BRAF inhibitor that inhibits both wild type and V600E mutant BRAF, and ABT-100, a farnesyltransferase inhibitor effective against various Ras mutations. Both have shown significant antitumor activity in preclinical models.

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Monoclonal Antibodies

ASP3082 for Cancer

Phase 1

Recruiting

Research Sponsored by Astellas Pharma Inc

Eligibility Criteria Checklist

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

Must have

- Female participant must not donate ova starting at first dose of study intervention and throughout the study period and for 6 months after study intervention administration.

Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of study intervention administration. Participants must have recovered from all radiation-related toxicities, not require corticosteroids (NOTE: Physiologic replacement dose of hydrocortisone or its equivalent [defined as up to 30 mg per day of hydrocortisone, 2 mg per day of dexamethasone, or up to 10 mg per day of prednisone] is permitted), and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (<= 2 weeks of radiotherapy) to non-central nervous system disease.

Must not have

Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of study intervention, left ventricular ejection fraction (LVEF) < 50% as determined by multigated acquisition (MUGA) scan or echocardiogram (ECHO) or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, obligate use of a cardiac pacemaker, or long QT syndrome.

Participant has leptomeningeal disease as a manifestation of the current malignancy.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 48 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called ASP3082 for adults with advanced cancers. The drug works by blocking harmful proteins. The study will determine the best dose and check for any side effects.

Who is the study for?

Adults with advanced solid tumors that can't be removed by surgery or have spread, and who have a specific mutation (KRAS G12D) after standard treatments or refusal of such therapies. They must be in good physical condition, not pregnant, agree to contraception use, and have recovered from previous treatment side effects.

What is being tested?

The trial is testing ASP3082 alone and combined with cetuximab in adults with certain solid tumors having the KRAS G12D mutation. It's an open-label study where participants know what they're receiving. The goal is to determine safe dosages and monitor how well patients tolerate the treatments over multiple cycles.

What are the potential side effects?

Potential side effects are not explicitly listed but may include typical reactions to cancer medications like infusion-related discomfort, organ inflammation, fatigue, digestive issues, blood disorders, increased infection risk as well as any adverse events observed during the trial.

Eligibility Criteria

Inclusion Criteria

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

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I will not donate eggs during and for 6 months after the study.

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I finished any radiotherapy 14 days ago, have no side effects, and don't need steroids.

Select...

It's been over 21 days or 5 half-lives since my last cancer treatment before starting the study.

Select...

I agree not to breastfeed during and for 6 months after the study.

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I can care for myself and am up and about more than 50% of my waking hours.

Exclusion Criteria

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

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I have not had a heart attack or severe heart issues in the last 6 months.

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My cancer has spread to the lining of my brain and spinal cord.

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I had to stop taking cetuximab because it was causing me severe side effects.

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I have active hepatitis B or C.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 48 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 48 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 48 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

Incidence of Dose Limiting Toxicities (DLTs)

Number of Participants with Adverse Events (AEs)

Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status

+5 more

Secondary study objectives

Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples

Disease Control Rate (DCR) per RECIST v 1.1

Duration of Response (DOR) per RECIST v 1.1

+5 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

7Treatment groups

Experimental Treatment

Group I: Treatment naive PDAC cohort ASP3082 + Nab-Paclitaxel + GemcitabineExperimental Treatment2 Interventions

Upon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with Nab-P + GEM (nanoparticle albumin-bound-paclitaxel plus gemcitabine) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.

Group II: Treatment naive PDAC cohort ASP3082 + FOLFIRINOXExperimental Treatment4 Interventions

Upon completion of dose escalation (part 1), participants with KRAS G12D mutant will receive ASP3082 in combination with FOLFIRINOX (leucovorin \[LV\]/fluorouracil \[5-FU\]/irinotecan/oxaliplatin) with dose level(s) selected from dose escalation (part 1) in a 28-day cycle.

Group III: ASP3082 Dose Expansion (Monotherapy Part 2)Experimental Treatment1 Intervention

Participants will receive ASP3082 with dose level(s) selected from dose escalation (part 1) in a 21-day cycle.

Group IV: ASP3082 Dose Escalation (Monotherapy Part 1)Experimental Treatment1 Intervention

Participants will receive ASP3082 in a 21-day cycle.

Group V: ASP3082 China Safety CohortExperimental Treatment1 Intervention

Participants will receive ASP3082 with dose level selected from dose escalation (Monotherapy part 1) in a 21-day cycle.

Group VI: ASP3082 + Cetuximab Dose Expansion (Combination Therapy Part 2)Experimental Treatment2 Interventions

Participants will receive ASP3082 or ASP3082 + Cetuximab with dose level(s) selected from dose escalation (part 1) in a 21-day cycle. Cetuximab will be administered weekly.

Group VII: ASP3082 + Cetuximab Dose Escalation (Combination Therapy Part 1)Experimental Treatment2 Interventions

Participants will receive ASP3082 in a 21-day cycle. Cetuximab will be administered weekly.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Leucovorin

2005

Completed Phase 4

~6010

Irinotecan

2017

Completed Phase 3

~2590

Gemcitabine

2017

Completed Phase 3

~1920

Fluorouracil

2014

Completed Phase 3

~11700

Cetuximab

2011

Completed Phase 3

~2480

0 / 9Eligibility 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

Targeted therapies for solid tumors, such as ASP3082, work by inhibiting abnormal proteins produced by specific genetic mutations like the G12D mutation in the KRAS gene. This is crucial for patients because it directly disrupts the cancer's growth and survival pathways. Similar treatments include tyrosine kinase inhibitors (TKIs) and monoclonal antibodies, which target specific enzymes and growth factor receptors on cancer cells. These therapies offer a personalized approach, potentially improving outcomes and reducing side effects compared to traditional chemotherapy.

Molecular-targeting therapies against quantitative abnormalities in gene expression with malignant tumors.