ASP3082 for Cancer

Recruiting at 59 trial locations

Overseen By Astellas Pharma Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Astellas Pharma Inc

Must not be taking: KRAS inhibitors

Disqualifiers: CNS metastases, Active hepatitis, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

651 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ASP3082 for individuals with advanced solid tumors that have a specific gene change known as KRAS G12D. The trial aims to determine the safety and tolerability of ASP3082, both alone and in combination with other cancer treatments like cetuximab (a monoclonal antibody used for certain cancers). Participants will receive the treatment in cycles through an infusion directly into a vein. The trial seeks participants with tumors that have the KRAS G12D mutation and who have not succeeded with standard treatments. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must have completed any prior cancer treatments at least 21 days before starting the study, and any radiotherapy at least 14 days prior. It's best to discuss your specific medications with the study team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ASP3082 has been tested for safety and effectiveness in patients with certain cancers, such as pancreatic, colorectal, and non-small cell lung cancer. In these studies, ASP3082 was used alone (monotherapy). Among 111 patients, results indicated that ASP3082 was generally well-tolerated, with most side effects being mild to moderate, such as tiredness or nausea.

When combined with cetuximab, a cancer treatment known to cause skin reactions, ASP3082 maintained a manageable safety profile. Some patients experienced a rash or itchiness, common side effects of cetuximab.

These findings suggest that ASP3082, whether used alone or with cetuximab, is mostly well-tolerated. However, as this study is in an early phase, the complete safety profile is still under investigation. Participants should discuss potential risks and benefits with their healthcare provider before joining the trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about ASP3082 because it targets the KRAS G12D mutation, a common driver in certain cancers like pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). Unlike standard treatments that may not specifically address this mutation, ASP3082 aims to tackle the cancer at a genetic level. This specificity could potentially lead to more effective outcomes and less collateral damage to healthy cells. Additionally, ASP3082 is being tested in combination with various chemotherapy and immunotherapy agents, which might enhance its impact and offer new hope for patients with these challenging cancers.

What evidence suggests that this trial's treatments could be effective for advanced solid tumors with KRAS G12D mutation?

Research has shown that ASP3082 has promising effects against tumors in lab studies. For cancers with the KRAS G12D mutation, ASP3082 helped shrink tumors in various tests. In one study with doses between 300–600 mg, 23.1% of patients with non-small cell lung cancer (NSCLC) experienced tumor shrinkage, and 84.6% had stabilized disease. These findings suggest that ASP3082 may be effective for tumors with the KRAS G12D mutation. In this trial, researchers are testing ASP3082 in various treatment arms, including combinations with other treatments like cetuximab and chemotherapy, to evaluate its potential for enhanced effectiveness. This combination approach might improve outcomes for patients with specific cancer mutations. ^{1 2 4 5 6}

Who Is on the Research Team?

Medical Director

Principal Investigator

Astellas Pharma Inc

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

I agree to provide recent or archived tumor samples for the study.

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

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

Exclusion Criteria

I have brain metastases but they are either symptom-free or treated.

I will need additional cancer treatment while on the study.

I haven't needed treatment for another cancer in the last 2 years, except for certain skin, bladder, cervix, or breast conditions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation (Part 1)

Participants receive escalating doses of ASP3082, alone or with cetuximab, to determine suitable doses for Part 2

21-28 days per cycle

Weekly visits for cetuximab administration

Dose Expansion (Part 2)

Participants receive ASP3082, alone or in combination with chemotherapy agents, at doses determined in Part 1

21-28 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 48 months

What Are the Treatments Tested in This Trial?

Interventions

• ASP3082
• Cetuximab

Trial Overview 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.

How Is the Trial Designed?

Group I: Treatment naive PDAC cohort ASP3082 + Nab-Paclitaxel + Gemcitabine Experimental Treatment 3 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 + FOLFIRINOX Experimental Treatment 5 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 Treatment 1 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 Treatment 1 Intervention

Participants will receive ASP3082 in a 21-day cycle.

Group V: ASP3082 China Safety Cohort Experimental Treatment 1 Intervention

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

Group VI: ASP3082 + Pembrolizumab - NSCLC Experimental Treatment 2 Interventions

Participants with KRAS G12D mutant will receive ASP3082 in combination with pembrolizumab in a 21-day cycle.

Group VII: ASP3082 + Docetaxel - NSCLC Experimental Treatment 2 Interventions

Participants with KRAS G12D mutant will receive ASP3082 in combination with docetaxel in a 21-day cycle.

Group VIII: ASP3082 + Cetuximab Dose Expansion (Combination Therapy Part 2) Experimental Treatment 2 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 IX: ASP3082 + Cetuximab Dose Escalation (Combination Therapy Part 1) Experimental Treatment 2 Interventions

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

Group X: ASP3082 + (Cisplatin or Carboplatin) and Pemetrexed +/- Pembrolizumab - NSCLC Experimental Treatment 5 Interventions

Participants with KRAS G12D mutant will receive ASP3082 in combination with platinum-based chemotherapy (cisplatin or carboplatin) and pemetrexed, with or without pembrolizumab in a 21-day cycle.

Who Is Running the Clinical Trial?

Astellas Pharma Inc

Lead Sponsor

Trials

700

Recruited

236,000+

Headquarters

Tokyo, Japan

Top Products

- Xtandi (enzalutamide) for prostate cancer, - Xospata (gilteritinib) for AML, - Padcev (enfortumab vedotin) for bladder cancer, - Prograf (tacrolimus) for organ rejection prevention

Tadaaki Taniguchi

Astellas Pharma Inc

Chief Medical Officer since 2023

MD, PhD

Naoki Okamura

Astellas Pharma Inc

Chief Executive Officer since 2023

University of Tokyo, Faculty of Pharmacy

Published Research Related to This Trial

A virtual interdisciplinary communication workshop was found to be feasible and acceptable for improving communication among oncology team members, based on feedback from 87 patients and 56 clinicians.

The workshop highlighted areas for improvement in communication practices, suggesting that targeted interventions can enhance patient care and safety in ambulatory oncology settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and Evaluation of a Data-Driven, Interactive Workshop to Facilitate Communication and Teamwork in Ambulatory Medical Oncology Settings. Blok, AC., Costa, DK., Wright, NC., et al.[2023]

A total of 3120 adverse event cases related to avapritinib were reported to the FDA, with 44% occurring within the first 30 days of treatment, highlighting the importance of monitoring patients closely during this period.

The study found that elderly male patients are at a higher risk for serious adverse events, indicating that clinicians should exercise caution when prescribing avapritinib to this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A post-marketing pharmacovigilance study of avapritinib: Adverse event data mining and analysis based on the United States Food and Drug Administration Adverse Event Reporting System database. Rong, L., Xie, M., Jiang, M., et al.[2023]

In a study of 66 patients with operable stage III non-small cell lung cancer (NSCLC), the combination of Camrelizumab with Docetaxel and Cisplatin showed good overall safety, with most adverse events (AEs) being mild (grade 1-2) and only 9.1% being severe (grade 3-4).

The supervision of adverse events during neoadjuvant therapy not only helped in managing complications but also led to an improvement in patients' quality of life, indicating that careful monitoring can enhance treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of Adverse Events Supervision in Clinical Trials in Neoadjuvant Treatment of Operable Stage III NSCLC]. Zhang, Y., Zhou, S., Tao, W., et al.[2023]

A meta-analysis of 53 Phase II/III/IV trials involving nearly 20,000 patients revealed that molecular target anticancer drugs significantly increase the risk of serious adverse events (SAEs) by 57% and fatal adverse events (FAEs) by 51% compared to placebo.

The overall incidence rates for SAEs and FAEs were found to be 26.9% and 2.3%, respectively, highlighting the need for careful monitoring and preventive measures for patients receiving these treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk of serious adverse event and fatal adverse event with molecular target anticancer drugs in cancer patients: A meta-analysis. Wang, Z., Yang, X., Wang, J., et al.[2020]

Only 5.3% of dose-finding oncology trials included patient-reported outcomes (PROs), indicating that their use is still quite limited despite a gradual increase over time.

Among completed trials, only 19.5% reported PRO results on ClinicalTrials.gov, highlighting a need for better standardization and reporting practices for PROs in oncology research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov. Lai-Kwon, J., Yin, Z., Minchom, A., et al.[2023]

Citations

1. annalsofoncology.org annalsofoncology.org/article/S0923-7534(24)02194-X/fulltext

608O Preliminary safety and clinical activity of ASP3082, a ... The ongoing study suggests that ASP3082, a novel KRAS G12D degrader, has an acceptable safety profile and promising antitumor activity, especially in pts with ...

2. astellas.com astellas.com/content/dam/astellas-com/global/en/documents/product-meetings/asp3082-targeted-protein-degradation-online-meeting-september-27-2024-presentation-material-en-fy2021.pdf

asp3082-targeted-protein-degradation- ... ... NSCLC, non-small cell lung cancer; CRC, colorectal cancer. ASP3082 monotherapy QW. Characteristic. 300–600mg (n = 48). Overall (N = 111). Median ...

3. nature.com nature.com/articles/s42004-025-01662-4

Discovery of KRAS(G12D) selective degrader ASP3082 ASP3082 showed potent anti-tumor activity and achieved tumor regression in multiple KRAS(G12D)-mutated cancer xenograft models with once- or ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12207871/

KRAS mutated NSCLC: past, present, and future directions in ... Lab studies have shown a higher activation and expression of genes correlating with T cell mobilization and antigen expression in the tumor ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05382559

A Study of ASP3082 in Adults With Advanced Solid Tumors This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP3082. The study aims to check how ...

6. kraskickers.org kraskickers.org/post/preliminary-safety-and-clinical-activity-of-asp3082-a-first-in-class-kras-g12d-selective-protein-d

Preliminary safety and clinical activity of ASP3082, a first-in ... A second phase I dose-escalation study investigated the clinical activity of the first-in-class KRAS G12D selective protein degrader ASP3082 in 111 patients.