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History of Changes for Study: NCT04727554
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors
Latest version (submitted November 16, 2022) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 January 25, 2021 None (earliest Version on record)
2 March 4, 2021 Study Status
3 May 5, 2021 Recruitment Status, Study Status, Contacts/Locations and Oversight
4 May 20, 2021 Contacts/Locations and Study Status
5 May 21, 2021 Study Status
6 June 2, 2021 Contacts/Locations and Study Status
7 June 16, 2021 Study Status and Contacts/Locations
8 July 29, 2021 Study Status and Contacts/Locations
9 August 11, 2021 Study Status and Contacts/Locations
10 September 1, 2021 Study Status and Contacts/Locations
11 September 8, 2021 Contacts/Locations and Study Status
12 September 15, 2021 Contacts/Locations and Study Status
13 September 29, 2021 Contacts/Locations and Study Status
14 November 24, 2021 Study Status, Contacts/Locations, Conditions and Study Description
15 April 6, 2022 Study Status and Contacts/Locations
16 May 9, 2022 Recruitment Status, Study Status, Contacts/Locations and Study Design
17 November 16, 2022 Study Status
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Study NCT04727554
Submitted Date:  January 25, 2021 (v1)

Open or close this module Study Identification
Unique Protocol ID: 20190136
Brief Title: Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors
Official Title: A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors
Secondary IDs:
Open or close this module Study Status
Record Verification: December 2020
Overall Status: Not yet recruiting
Study Start: February 3, 2021
Primary Completion: July 12, 2024 [Anticipated]
Study Completion: July 12, 2024 [Anticipated]
First Submitted: January 25, 2021
First Submitted that
Met QC Criteria:
January 25, 2021
First Posted: January 27, 2021 [Actual]
Last Update Submitted that
Met QC Criteria:
January 25, 2021
Last Update Posted: January 27, 2021 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Amgen
Responsible Party: Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: Yes
U.S. FDA-regulated Device: No
Data Monitoring:
Open or close this module Study Description
Brief Summary: The primary objective of this study is to evaluate the safety, tolerability, and maximum tolerated dose (MTD)/maximum tolerated combination dose (MTCD) or recommended phase 2 dose (RP2D) of AMG 994 as monotherapy and AMG 994 in combination with AMG 404 in participants with advanced solid tumors.
Detailed Description:
Open or close this module Conditions
Conditions: Advanced Solid Tumors
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Treatment
Study Phase: Phase 1
Interventional Study Model: Sequential Assignment
Number of Arms: 4
Masking: None (Open Label)
Allocation: Non-Randomized
Enrollment: 214 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Part 1a: Dose Exploration
Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
Drug: AMG 994
Administered as an intravenous (IV) infusion.
Drug: AMG 404
Administered as an intravenous (IV) infusion.
Experimental: Part 1b: Dose Exploration
Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
Drug: AMG 994
Administered as an intravenous (IV) infusion.
Drug: AMG 404
Administered as an intravenous (IV) infusion.
Experimental: Part 1c: Dose Exploration
Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.
Drug: AMG 994
Administered as an intravenous (IV) infusion.
Drug: AMG 404
Administered as an intravenous (IV) infusion.
Experimental: Part 2: Dose Expansion
Participants will be administered with the MTD or RP2D of AMG 994 identified in the dose escalation part of the study, in combination with AMG 404.
Drug: AMG 994
Administered as an intravenous (IV) infusion.
Drug: AMG 404
Administered as an intravenous (IV) infusion.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. Number of Participants with Dose Limiting Toxicities (DLTs)
[ Time Frame: 28 days ]

2. Number of Participants with Treatment-emergent Adverse Events (TEAEs)
[ Time Frame: Up to 36 months ]

3. Number of Participants with Treatment-Related Adverse Events
[ Time Frame: Up to 36 months ]

4. Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurements
[ Time Frame: Up to 24 months ]

5. Number of Participants Who Experience a Clinically Significant Change from Baseline in Electrocardiogram (ECG) Results
[ Time Frame: Up to 24 months ]

6. Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
[ Time Frame: Up to 30 months ]

Secondary Outcome Measures:
1. Objective Response (OR)
[ Time Frame: Up to 36 months ]

2. Duration of Response (DOR)
[ Time Frame: Up to 36 months ]

3. Overall Survival (OS)
[ Time Frame: Up to 36 months ]

4. Progression-Free Survival (PFS)
[ Time Frame: Up to 36 months ]

5. Time to Progression
[ Time Frame: Up to 36 months ]

6. Time to Subsequent Therapy
[ Time Frame: Up to 36 months ]

7. Maximum Observed Serum Concentration (Cmax) of AMG 994
[ Time Frame: Up to 30 months ]

8. Maximum Observed Serum Concentration (Cmax) of AMG 404
[ Time Frame: Up to 30 months ]

9. Minimum Observed Serum Concentration (Cmin) of AMG 994
[ Time Frame: Up to 30 months ]

10. Minimum Observed Serum Concentration (Cmin) of AMG 404
[ Time Frame: Up to 30 months ]

11. Area Under the Serum Concentration-time Curve (AUC) of AMG 994
[ Time Frame: Up to 30 months ]

12. Area Under the Serum Concentration-time Curve (AUC) of AMG 404
[ Time Frame: Up to 30 months ]

13. Half-life (t1/2) of AMG 994
[ Time Frame: Up to 30 months ]

14. Half-life (t1/2) of AMG 404
[ Time Frame: Up to 30 months ]

Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age: 100 Years
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

Inclusion Criteria:

  • Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
  • Age ≥ 18 years at the time of signing informed consent.
  • Life expectancy of > 3 months, in the opinion of the investigator.
  • Participant must have histologically or cytologically proven metastatic or locally advanced solid tumors of known MSLN expression who have relapsed after and/or are refractory to established and available therapies with known clinical benefit, for which:
    • No standard systemic therapy exists; or
    • Standard systemic therapy has failed or is not available.
  • Dose Expansion (Part 2): Participant must have one of the following malignancies: mesothelioma, pancreatic adenocarcinoma, MSLN positive NSCLC squamous cell carcinoma or adenocarcinoma, high grade serous ovarian carcinoma.
  • At least 1 measurable or evaluable lesion as defined by modified RECIST 1.1 guidelines.
  • Participants must be willing to undergo a biopsy prior to enrollment and during treatment with AMG 994.
  • Participants with treated brain metastases are eligible provided they meet the following criteria:
    • Definitive therapy was completed at least 2 weeks prior to enrollment.
    • No evidence of radiographic central nervous system (CNS) progression or CNS disease following definitive therapy and by the time of study screening. Patients manifesting progression in lesions previously treated with stereotactic radiosurgery may still be eligible if pseudoprogression can be demonstrated by appropriate means and after discussion with the medical monitor.
    • Any CNS disease is asymptomatic, any neurologic symptoms due to CNS disease have returned to baseline, or non-serious CNS diseases that are asymptomatic and deemed irreversible (eg, peripheral neuropathy), the patient is off steroids for at least 7 days (physiologic doses of steroids are permitted), and the patient is off or on stable doses of anti-epileptic drugs for malignant CNS disease and has not had a seizure within 1 month prior to the screening visit.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of ≤ 2.
  • Hematologic function, as follows (transfusions or growth factor support must not be administered within 7 days prior to obtaining screening labs):
    • Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
    • Platelet count ≥ 75 x 109/L
    • Hemoglobin ≥ 9 g/dL
  • Adequate renal laboratory assessments, as follows:

    • Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 45 mL/min/1.73 m2

  • Hepatic function, as follows:
    • Total bilirubin (TBL) ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for participants with liver metastasis
    • Aspartate transaminase (AST) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis
    • Alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis
    • Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN for participants with liver metastasis

Exclusion Criteria:

Disease Related

  • Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal disease.

Other Medical Conditions

  • History of other malignancy within the past 2 years, with the following exception[s]:
    • Malignancy treated with curative intent and with no known active disease present for ≥ 3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
    • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
    • Adequately treated cervical carcinoma in situ without evidence of disease.
    • Adequately treated breast ductal carcinoma in situ without evidence of disease.
    • Prostatic intraepithelial neoplasia without evidence of prostate cancer.
    • Adequately treated urothelial papillary noninvasive carcinoma or carcinoma in situ.
  • Participants with NSCLC squamous cell carcinoma (Part 1), MSLN negative NSCLC squamous cell carcinoma (Part 2), or MSLN negative NSCLC adenocarcinoma (Part 2) once the participant has been screened for MSLN expression.
  • Participants with sarcomatoid mesothelioma and small cell lung cancer will be excluded from both the Dose Exploration (Part 1) and Dose Expansion (Part 2) parts of the study.
  • History of solid organ transplantation.
  • Major surgery within 28 days of study day 1.

Prior/Concomitant Therapy

  • Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 21 days prior to study day 1.
  • Treatment with a checkpoint inhibitor within 9 weeks prior to study day 1.
  • Live vaccine therapy within 4 weeks prior to study drug administration.
  • Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid defined as > 10 mg prednisone daily or equivalent. Steroids with no minimal systemic effect (such as topical or inhalation) are permitted.

Prior/Concurrent Clinical Study Experience

  • Currently receiving treatment in another investigational device or drug study, or less than 21 days prior to study day 1 since ending treatment on another investigational device or drug study(ies).
  • Evidence of active or radiological sequelae of non-infectious pneumonitis.
  • History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis.
  • History of allergic reactions or acute hypersensitivity reaction to antibody therapies.
  • Positive/non-negative test results for human immunodeficiency virus (HIV).
  • Hepatitis B and C based on the following results:
    • Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
    • Negative HBsAG and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
    • Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
  • Active infection requiring oral or intravenous therapy.
  • Active or history of any autoimmune disease or immunodeficiencies. Participants with diabetes Type 1, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.
  • Myocardial infarction within 6 months of study day 1, symptomatic congestive heart failure (New York Heart Association > class II), unstable angina, or cardiac arrhythmia requiring medication.
  • Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or are stable and well controlled with minimal, local, or noninvasive intervention AND there is agreement to allow by both the investigator and the Amgen Medical Monitor.
    • Any history of grade 3 or higher colitis, pneumonitis, or neurological toxicity OR
    • Unresolved toxicities from prior checkpoint inhibitor therapy, defined as not having resolved to CTCAE v5.0 grade 1.
    • Exception: - clinically stable hypothyroid status managed with hormone replacement therapy, is permitted

Other Exclusions

  • Female participant is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
  • Female participants of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
  • Female participants of childbearing potential with a positive pregnancy test assessed at day 1 by a serum pregnancy test.
  • Male participants with a female partner of childbearing potential who are unwilling to practice sexual abstinence (refrain from heterosexual intercourse) or use contraception during treatment and for an additional 8 months after the last dose of AMG 994 and/or AMG 404.
  • Male participants unwilling to abstain from donating sperm during treatment and for an additional 8 months after the last dose of AMG 994 and/or AMG 404.
  • Participant has known sensitivity to any of the products or components to be administered during dosing.
  • Participant likely to not be available to complete all protocol-required study visits or procedures, and/or to comply with all required study procedures to the best of the participant and investigator's knowledge.
  • History or evidence of any other clinically significant disorder, condition or disease (with the exception of those outlined above) that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participant safety or interfere with the study evaluation, procedures or completion.
Open or close this module Contacts/Locations
Central Contact Person: Amgen Call Center
Telephone: 866-572-6436
Email: medinfo@amgen.com
Study Officials: MD
Study Director
Amgen
Locations:
Open or close this module IPDSharing
Plan to Share IPD: Yes
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Supporting Information:
Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame:
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Access Criteria:
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
URL: http://www.amgen.com/datasharing
Open or close this module References
Citations:
Links: Description: AmgenTrials clinical trials website
Available IPD/Information:

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