A Phase 1 Study of ASP5834 in Participants With Locally Advanced (Unresectable) or Metastatic Solid Tumor Malignancies With KRAS Mutations or KRAS Amplifications

Plain English Summary

A Study to Find a Suitable Dose of ASP5834 in Adults With Solid Tumors is a Phase 1 clinical trial sponsored by Astellas Pharma Inc studying Solid Tumor, Non-Small-Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Colorectal Cancer. This trial tests a new drug called ASP5834, alone or with another drug (panitumumab), to see if it's safe and to find the right dose. It is for adults with advanced solid tumors that have specific changes (mutations or amplifications) in a gene called KRAS. Participation involves receiving the study drug(s) through an IV infusion and regular check-ups to monitor for side effects and how the treatment is working. Alternative treatments may include standard chemotherapy, targeted therapies, or immunotherapy, depending on the specific cancer type and prior treatments. The trial aims to enroll 364 participants.

Official Summary

Genes contain genetic code which tell the body which proteins to make. Many types of cancer are caused by changes, or mutations, in a gene called KRAS. Researchers are looking for ways to stop the actions of abnormal proteins made from the mutated KRAS gene. ASP5834 is being studied in people with solid tumors who have certain KRAS gene mutations. Some people with solid tumors of the colon or rectum (colorectal cancer), will be given ASP5834 with panitumumab. Panitumumab is a treatment for colorectal cancer. In this study, the researchers will learn how ASP5834 is processed by and acts upon the body. This information will help find a suitable dose of ASP5834 and check for any potential medical problems from the treatment. The main aims of this study are to check the safety of ASP5834 given by itself or given with panitumumab, and how well it is tolerated; and to find a suitable dose of ASP5834 given by itself or given with panitumumab. People in this study will be adults with locally advanced, unresectable, or metastatic solid tumors with certain KRAS gene mutations. 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. They either haven't responded to standard treatment or couldn't be given standard treatment. The key reasons people cannot take part are if they have specific uncontrollable cancers such as symptomatic or untreated cancers in nervous system, have specific heart conditions, swelling and irritation of lung tissues (pneumonitis or interstitial lung disease, also called ILD), infections, or have recently had a stroke or a bleed on the brain. In this study, ASP5834 is being given to humans for the first time. This is an open-label study. This means that people in this study and clinic staff will know that they will receive ASP5834 by itself or ASP5834 with panitumumab. This study will be in 2 parts: Part 1 is called

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults with solid tumors (like lung, pancreatic, or colorectal cancer) that have spread or cannot be removed by surgery, and have specific KRAS gene changes. Individuals who have not responded to or cannot receive standard treatments. People with certain serious health conditions, such as active brain tumors, recent stroke, or lung inflammation, may not be eligible. Age is not specified as a strict exclusion, but participants must be adults. This trial is studying Solid Tumor, Non-Small-Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcomes measure how safe the drug is and what side effects occur, helping doctors understand the risks and benefits of ASP5834. The specific primary outcome measures are: Incidence of Dose Limiting Toxicities (DLTs) (Dose Escalation only) (Up to 21 days); Number of participants with Adverse Events (AEs) (Up to 40 months); Number of Participants with Serious Adverse Events (SAEs) (Up to 40 months); Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to 40 months); Number of Participants with Eye Exam abnormalities and/or Adverse Events (AEs) (Up to 39 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 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a significant unmet need by investigating a novel therapy for patients with KRAS-mutated solid tumors, a challenging group of cancers with limited effective treatment options. This research targets Solid Tumor, Non-Small-Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma, Colorectal Cancer, where improved treatment options are needed.

Investor Insight

This Phase 1 trial represents an early-stage investment in a potentially new targeted therapy for a common and difficult-to-treat cancer mutation, with a high probability of informing future developme Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific KRAS mutation your cancer has and if it matches the trial's requirements. Understand that this is an early-phase study, meaning the drug is being tested for the first time in humans, and the full effects are not yet known. Be prepared for regular clinic visits for drug infusions, blood tests, scans, and to report any new symptoms or side effects. This trial is currently recruiting participants. The trial is being conducted at 18 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: 364 participants

Interventions

• DRUG: ASP5834 — Intravenous infusion
• DRUG: panitumumab — Intravenous infusion

Primary Outcomes

• Incidence of Dose Limiting Toxicities (DLTs) (Dose Escalation only) (Up to 21 days)
• Number of participants with Adverse Events (AEs) (Up to 40 months)
• Number of Participants with Serious Adverse Events (SAEs) (Up to 40 months)
• Number of participants with laboratory value abnormalities and/or adverse events (AEs) (Up to 40 months)
• Number of Participants with Eye Exam abnormalities and/or Adverse Events (AEs) (Up to 39 months)

Secondary Outcomes

• Objective Response Rate (ORR) of ASP5834 per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (Up to 45 months)
• Duration of Response (DOR) of ASP5834 per RECIST v1.1 (Up to 45 months)
• Disease Control Rate (DCR) of ASP5834 per RECIST v1.1 (Up to 45 months)
• Progression Free Survival (PFS) per RECIST v1.1 (Up to 45 months)
• Overall Survival (OS) (Up to 45 months)

Full Eligibility Criteria

Inclusion Criteria:

* Participant has histologically confirmed locally advanced (unresectable) or metastatic solid tumor malignancy with a documented Kirsten rat sarcoma viral oncogene homolog (KRAS) G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification (copy number \>/= 4) determined by local testing.

  * For a participant with a documented KRAS amplification, only those with no other co-occurring KRAS mutation or those with a co-occurring KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation are eligible.
  * Unique to Europe (EU): Only participants who have pre-existing local results can be enrolled.
* For the ASP5834 monotherapy dose escalation part, participant with any histologically confirmed locally advanced (unresectable) or metastatic solid tumor malignancy is eligible. Participant must have received prior standard therapy in the advanced setting, and the investigator does not see any further clinical benefit from continuing such therapy or the participant is ineligible to receive standard approved therapies.
* For the ASP5834 monotherapy dose expansion part, the following criteria apply:

  * \[pancreatic ductal adenocarcinoma (PDAC) Expansion Cohort(s)\] Participant has histologically confirmed locally advanced (unresectable) or metastatic PDAC.
  * \[PDAC Expansion Cohort(s)\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation determined by local testing.
  * \[PDAC Expansion Cohort(s)\] Participant must have received standard therapy in the advanced setting, including prior therapy with a gemcitabine-based or fluoropyrimidine-based regimen or is ineligible for these therapies.
  * \[PDAC Expansion Cohort(s)\] No more than 2 prior lines of systemic therapy are allowed in the advanced setting (note: maintenance therapy does not count as a separate line of therapy).
  * \[PDAC Expansion Cohort(s)\] For a participant who received prior neoadjuvant or adjuvant chemotherapy and had recurrence on or within 6 months of completion of therapy, the neoadjuvant or adjuvant chemotherapy should be counted as a regimen in the advanced setting.
  * \[non-small cell lung cancer (NSCLC) Expansion Cohort(s)\] Participant has histologically confirmed locally advanced (unresectable) or metastatic NSCLC.
  * \[NSCLC Expansion Cohort(s)\] Participant has a documented KRAS G12V, G12D, G12R, G12A or G13D mutation determined by local testing.
  * \[NSCLC Expansion Cohort(s)\] Participant must have received standard therapy in the advanced setting, including prior platinum-based chemotherapy and checkpoint inhibitor therapy or is ineligible for these therapies. Participants with known actionable genomic alterations (AGA) must have received prior therapy with an approved targeted therapy in accordance with local requirements.
  * \[NSCLC Expansion Cohort(s)\] For a participant who has received prior neoadjuvant or adjuvant therapy and had recurrence during or within 6 months of completion of therapy, the neoadjuvant or adjuvant therapy should be counted as a regimen in the advanced setting (for those who received perioperative therapy, the entire course should be counted as therapy in the advanced setting).
  * \[NSCLC Expansion Cohort(s)\] For a participant with a history of unresectable Stage III disease who received prior multi-modal therapy and had recurrence on or within 6 months of completion of therapy, the multi-modal therapy should be counted as a therapy in the advanced setting. If chemoradiation was followed by treatment with checkpoint inhibitor therapy without documented progression between chemoradiation and checkpoint inhibitor therapy, the entire treatment course should be counted as therapy in the advanced setting.
  * \[Other Solid Tumor Expansion Cohort\] Participant has a histologically confirmed locally advanced (unresectable) or metastatic solid tumor type other than PDAC, colorectal cancer (CRC) or NSCLC.
  * \[Other Solid Tumor Expansion Cohort\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation or KRAS amplification (copy number \>/=4) determined by local testing.
  * \[Other Solid Tumor Expansion Cohort\] Participant must have received prior standard therapy in the advanced setting, and the investigator does not see any further clinical benefit from continuing such therapy or is ineligible to receive standard approved therapies.
* For ASP5834 combination therapy dose escalation and dose expansion parts, the following criteria apply:

  * \[CRC Dose Escalation and Dose Expansion Parts\] Participant has histologically confirmed locally advanced (unresectable) or metastatic adenocarcinoma of the colon or rectum.
  * \[CRC Dose Escalation and Dose Expansion Parts\] Participant has a documented KRAS G12V, G12D, G12C, G12R, G12A or G13D mutation determined by local testing.
  * \[CRC Dose Escalation and Dose Expansion Parts\] Participant must have received standard therapy in the advanced setting, including prior therapy with fluo

Trial Locations

• Winship Cancer Institute at Emory University, Atlanta, Georgia, United States
• Ochsner Health, Jefferson, Louisiana, United States
• START Midwest, Grand Rapids, Michigan, United States
• Washington University School of Medicine, St Louis, Missouri, United States
• Hackensack University Medical Center, Hackensack, New Jersey, United States
• Roswell Cancer Institute, Buffalo, New York, United States
• Memorial Sloan Kettering Cancer Center, New York, New York, United States
• University Hospitals - UH Cleveland Medical Center, Cleveland, Ohio, United States
• NEXT Oncology Dallas, Irving, Texas, United States
• NEXT Oncology Virginia, Fairfax, Virginia, United States
• ...and 8 more locations

Frequently Asked Questions

Related Conditions

• Solid Tumor Malignancies
• Non-Small-Cell Lung Cancer
• Pancreatic Ductal Adenocarcinoma
• Colorectal Cancer
• KRAS Mutations
• KRAS Amplifications
• Oncology
• Gastrointestinal Cancers
• Thoracic Cancers
• Targeted Therapy

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