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A Study of ASP3082 in Adults With Previously Treated Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05382559
Recruitment Status : Recruiting
First Posted : May 19, 2022
Last Update Posted : August 2, 2022
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc

Tracking Information
First Submitted Date  ICMJE May 16, 2022
First Posted Date  ICMJE May 19, 2022
Last Update Posted Date August 2, 2022
Actual Study Start Date  ICMJE June 8, 2022
Estimated Primary Completion Date May 31, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • Incidence of Dose Limiting Toxicities (DLTs) [ Time Frame: Up to 21 Days ]
    A DLT is defined as any event meeting the DLT criteria occurring within 21 days of first dose on Cycle 1 Day 1 (C1D1), excluding toxicities clearly related to disease progression or intercurrent illness.
  • Number of Participants with Adverse Events (AEs) [ Time Frame: Up to 50 months ]
    An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study IP, whether or not considered related to the study investigational product (IP). Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom or disease (new or exacerbated) temporally associated with the use of study IP. This includes events related to the comparator and events related to the (study) procedures.
  • Number of Participants with Serious Adverse Events (SAEs) [ Time Frame: Up to 50 months ]
    An SAE is defined as any untoward medical occurrence that, at any dose: Results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important events.
  • Number of Participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]
    Number of participants with potentially clinically significant laboratory values.
  • Number of Participants with electrocardiogram (ECG) abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]
    Number of participants with potentially clinically significant ECG values.
  • Number of Participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to 48 months ]
    Number of participants with potentially clinically significant vital sign values.
  • Number of Participants with physical exam abnormalities and/or adverse events [ Time Frame: Up to 48 months ]
    Number of participants with potentially clinically significant physical exam values.
  • Number of Participants with Eastern Cooperative Oncology Group (ECOG) performance status [ Time Frame: Up to 48 months ]
    The ECOG scale will be used to assess performance status. Grades range from 0 (fully active) to 5 (dead). Negative change scores indicate an improvement. Positive scores indicate a decline in performance.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2022)
  • Objective Response Rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [ Time Frame: Up to 48 months ]
    ORR is defined as the proportion of participants whose best overall response is rated as complete response (CR) or partial response (PR) per RECIST v1.1.
  • Duration of Response (DOR) per RECIST v 1.1 [ Time Frame: Up to 48 months ]
    DOR is measured from the time measurement criteria are first met for CR/PR (whichever is first recorded) until the first date of documented radiological disease progression per RECIST v1.1 or death in the absence of progression.
  • Disease Control Rate (DCR) per RECIST v 1.1 [ Time Frame: Up to 48 months ]
    DCR is defined as the proportion of participants whose best overall response is rated as CR, PR or SD based on RECIST v1.1.
  • Pharmacokinetics (PK) of ASP3082 in plasma: Area under the concentration-time curve (AUC) [ Time Frame: Up to 48 months ]
    AUC will be recorded from the PK plasma samples collected.
  • PK of ASP3082 in plasma: Maximum Concentration (Cmax) [ Time Frame: Up to 48 months ]
    Cmax will be recorded from the PK plasma samples collected.
  • PK of ASP3082 in plasma: concentration immediately prior to dosing at multiple dosing (Ctrough) [ Time Frame: Up to 48 months ]
    Ctrough will be recorded from the PK plasma samples collected.
  • PK of ASP3082 in plasma: Time of maximum concentration (tmax) [ Time Frame: Up to 48 months ]
    tmax will be recorded from the PK plasma samples collected.
  • Changes in Kirsten rat sarcoma (KRAS) viral oncogene homolog G12D in tumor samples [ Time Frame: Up to 48 months ]
    Changes in KRAS G12D in tumor samples will be measured.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ASP3082 in Adults With Previously Treated Solid Tumors
Official Title  ICMJE A Phase 1 Study of ASP3082 in Participants With Previously Treated Locally Advanced or Metastatic Solid Tumor Malignancies With KRAS G12D Mutation
Brief Summary

ASP3082 is a potential new treatment for people with certain solid tumors. Before ASP3082 is available as a treatment, the researchers need to understand how it is processed by and acts upon the body. This information will help find a suitable dose and check for potential medical problems from the treatment.

People in this study will be adults with locally advanced or metastatic solid tumors with changes in their KRAS gene (G12D mutation). Metastatic means the cancer has spread to other parts of the body. They will have been previously treated with all available standard therapies.

There are 2 main aims of this study. The first is to learn if people with certain solid tumors have any medical problems after receiving different doses of ASP3082. The second is to find a suitable dose of ASP3082 to use in future studies.

This study will be in 2 parts. In Part 1, different small groups of people will receive lower to higher doses of ASP3082. Any medical problems will be recorded at each dose. This is done to find suitable doses of ASP3082 to use in Part 2 of the study. The first group will receive the lowest dose of ASP3082. A medical expert panel will check the results from this group and decide if the next group can receive a higher dose of ASP3082. The panel will do this for each group until all groups have taken ASP3082 or until suitable doses have been selected for Part 2.

In Part 2, other different small groups of people will receive ASP3082 with the most suitable doses worked out from Part 1. This will help find a more accurate dose of ASP3082 to use in future studies.

ASP3082 will be given through a vein. This is called an infusion. Each treatment cycle is 21 days long. They will continue treatment until: they have medical problems from the treatment; their cancer gets worse; they start other cancer treatment; they ask to stop treatment; they do not come back for treatment.

People will visit the clinic on certain days during their treatment, with extra visits during the first 2 cycles of treatment. During these visits, the study doctors will check for any medical problems from ASP3082. At some visits, other checks will include a medical examination, laboratory tests and vital signs. Vital signs include temperature, pulse, breathing rate, and blood pressure. Also, blood and urine samples will be taken. Tumor samples will be taken during certain visits during treatment and when treatment has finished.

People will visit the clinic within 7 days after stopping treatment. The study doctors will check for any medical problems from ASP3082. Other checks will include a medical examination, laboratory tests and vital signs. Then, they may visit the clinic at 30 days and 90 days after stopping treatment. At the 30-day visit, the study doctors will check for any medical problems from ASP3082. People will have their vital signs checked and have some laboratory tests. At the 90-day visit, the study doctors will check for any medical problems from ASP3082 and people will have their vital signs checked. After this, people will continue to visit the clinic every 9 weeks. This is to check the condition of their cancer. They will do this until 45 weeks after treatment stopped, their cancer is worse, they start other cancer treatment, they ask to stop treatment, or they do not come back for treatment.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Solid Tumor
Intervention  ICMJE Drug: ASP3082
Intravenous Infusion
Study Arms  ICMJE
  • Experimental: ASP3082 Dose Escalation (Part 1)
    Participants will receive ASP3082 in a 21-day cycle.
    Intervention: Drug: ASP3082
  • Experimental: ASP3082 Dose Expansion (Part 2)
    Participants will receive ASP3082 with dose level(s) selected from dose escalation (part 1) in a 21-day cycle.
    Intervention: Drug: ASP3082
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 16, 2022)
136
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE May 31, 2026
Estimated Primary Completion Date May 31, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Participant has locally advanced (unresectable) or metastatic solid tumor malignancy with documented Kirsten rat sarcoma viral oncogene homolog [KRAS] G12D mutation and has progressed after receiving all available standard approved therapies (no limit to the number of prior treatment regimens). If KRAS mutation status is unknown, an archival tumor sample can be sent to the central lab during the prescreening/screening period.
  • Participant consents to provide tumor specimen in a tissue block or unstained serial slides or a tumor biopsy (core needle biopsy or excision) obtained after the last interventional treatment, but not more than 56 days prior to start of investigational product (IP). Participant also consents to provide a sample for tumor biopsy during the treatment period as indicated in the Schedule of Assessments.
  • Participant has at least 1 measurable lesion per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
  • Participant has an ECOG performance status of 0, 1 or 2.
  • Participant's last dose of prior antineoplastic therapy, including any immunotherapy, was 21 days or 5 half-lives, whichever is shorter, prior to initiation of IP administration.
  • Participant has completed any radiotherapy (including stereotactic radiosurgery) at least 14 days prior to the start of IP 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.
  • Participant's adverse events [AEs] (excluding alopecia) from prior therapy have improved to grade 1 or baseline within 14 days prior to start of IP.
  • Participant has adequate organ function as indicated by protocol laboratory value parameters (If a participant has received a recent blood transfusion, the laboratory tests must be obtained >= 28 days after any blood transfusion.).
  • Female participant is not pregnant and at least 1 of the following conditions apply:

    • Not a woman of childbearing potential (WOCBP).
    • WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 6 months after IP administration.
  • Female participant must agree not to breastfeed starting at screening and throughout the study period and for 6 months after IP administration.
  • Female participant must not donate ova starting at first dose of IP and throughout the study period and for 6 months after IP administration.
  • Male participant with female partner(s) of childbearing potential (including breastfeeding partner) must agree to use contraception throughout the treatment period and for 3 months after IP administration.
  • Male participant must not donate sperm during the treatment period and for 3 months after IP administration.
  • Male participant with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 3 months after IP administration.
  • Participant agrees not to participate in another interventional study while receiving IP (Participants who are currently in the follow-up period of an interventional clinical trial are allowed).

Exclusion Criteria

  • Participant has received investigational therapy within 21 days or 5 half-lives, whichever is shorter, prior to start of IP.
  • Participant has symptomatic or untreated central nervous system (CNS) metastases. Participants with asymptomatic, treated CNS metastases are eligible if they have been off corticosteroids and antiepileptic drugs for at least 14 days prior to start of IP.
  • Participant has leptomeningeal disease as a manifestation of the current malignancy.
  • Participant has a prior malignancy active (i.e., requiring treatment or intervention) within the previous 2 years, except for local malignancies that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix or breast, which are allowed.
  • Participant has a known or suspected hypersensitivity to ASP3082 or any components of the formulation used.
  • Participant with known history of positive hepatitis B surface antigen or isolated hepatitis B core antibody (including acute hepatitis B virus [HBV] or chronic HBV) or hepatitis C virus [HCV] (ribonucleic acid [RNA] detected by qualitative assay). HCV RNA testing is not required in participants with negative HCV antibody testing.
  • Participant has a known history of human immunodeficiency virus [HIV] infection. No HIV testing is required unless mandated by a local health authority.
  • Participant has had a myocardial infarction or unstable angina within 6 months prior to the start of IP or currently has an uncontrolled illness including, but not limited to symptomatic congestive heart failure, clinically significant cardiac disease, unstable angina pectoris, cardiac arrhythmia, complete left bundle branch block, obligate use of a cardiac pacemaker, long QT syndrome, or right bundle branch block with left anterior hemiblock (bifascicular block).
  • Participant has a corrected QT interval (single electrocardiogram [ECG]) using Fridericia's formula (QTcF) > 450 milliseconds (msec) during screening. ECGs will be performed in triplicate during screening.
  • Participant has received prior treatment with a specific KRAS G12D inhibitor.
  • Participant has an infection requiring systemic therapy (e.g., intravenous antibiotics) within 14 days prior to IP.
  • Participant is expected to require another form of antineoplastic therapy while on study treatment.
  • Participant has any condition which makes the participant unsuitable for study participation (such as psychiatric illness/social situations that would limit compliance with study requirements).
  • Participant has known history of COVID-19 positive polymerase chain reaction (PCR) test within 4 weeks prior to the start of study treatment.
  • Participant has had major surgery within 4 weeks prior to first dose of IP.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Astellas Pharma Inc. 800-888-7704 astellas.registration@astellas.com
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05382559
Other Study ID Numbers  ICMJE 3082-CL-0101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Access to anonymized individual participant level data collected during the study, in addition to study-related supporting documentation, is planned for studies conducted with approved product indications and formulations, as well as compounds terminated during development. Studies conducted with product indications or formulations that remain active in development are assessed after study completion to determine if Individual Participant Data can be shared. Conditions and exceptions are described under the Sponsor Specific Details for Astellas on www.clinicalstudydatarequest.com.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: Access to participant level data is offered to researchers after publication of the primary manuscript (if applicable) and is available as long as Astellas has legal authority to provide the data.
Access Criteria: Researchers must submit a proposal to conduct a scientifically relevant analysis of the study data. The research proposal is reviewed by an Independent Research Panel. If the proposal is approved, access to the study data is provided in a secure data sharing environment after receipt of a signed Data Sharing Agreement.
URL: https://www.clinicalstudydatarequest.com
Current Responsible Party Astellas Pharma Inc
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Astellas Pharma Inc
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Medical Director Astellas Pharma Inc
PRS Account Astellas Pharma Inc
Verification Date July 2022

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP