Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors

NCT04727554 | Completed Phase 1 Results FDA Drug

• 1 other identifier: 20190136
• Study Type: interventional
• Target: 11
• Locations: 10 countries
• Sites: 17

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.

Conditions

Advanced Solid Tumors

Keywords

Mesothelin expression

Outcome Measures

Primary Outcomes (2)

• Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)

  DLTs were defined as: * Grade 5 events * Grade 4 neutropenia/thrombocytopenia of any duration * Grade 3 thrombocytopenia w/ clin significant bleeding or lasting \>7 days * Febrile neutropenia * Grade 4 anemia * Grade 3/4 non-hematologic toxicity, except: Grade 3 nausea/vomiting or diarrhea \< 72 hours; Grade 3 fatigue \< 1 week; Asymptomatic grade 3 electrolyte abnormalities that last \< 72 hours, are not clinically complicated, and resolve spontaneously or respond to conventional medical interventions; Grade 3 amylase/ lipase elevations; Other laboratory parameters of grade 3, not considered clinically relevant and improved to grade ≤ 2 within 72 hours. * Any grade 3 event requiring hospitalization * Recurrent grade 2 pneumonitis * Delay in cycle 2 treatment for \> 14 days due to an adverse event in the dose escalation portion of the study * Any event requiring discontinuation of AMG 994

  Up to Day 28 of Cycle 1 (one cycle = 28 days)

• Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)

  TEAEs were those that occurred after the first intervention dose. A serious adverse event (SAE) included outcomes such as death, life-threatening situations, hospitalization or an extended hospital stay, significant incapacity, congenital defects, or other crucial medical events. AE severity followed the CTCAE Version 5.0 scale: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), and grade 5 (death). Clinically significant laboratory results or other assessments (e.g., ECGs, scans, vital signs) that worsened from baseline and were deemed important by the investigator, independent of disease progression, were also considered.

  From first dose of investigational product through 140 days after last dose (AMG 994 or AMG 404, whichever is later), or end of study (whichever is first); median (min, max) duration was 12.5 ( 1.48, 19.32) months.

Secondary Outcomes (18)

• Objective Response (OR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Up to approximately 19.32 months

• Duration of Response (DoR) Per Modified RECIST 1.1

  Up to approximately 19.32 months

• Overall Survival (OS) Per Modified RECIST 1.1

  Up to approximately 19.32 months

• Progression-free Survival Per Modified RECIST 1.1

  Up to approximately 19.32 months

• Time to Progression (TTP) Per Modified RECIST 1.1

  Up to approximately 19.32 months

Study Arms (4)

Part 1a: Dose Exploration

EXPERIMENTAL

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Drug: AMG 994; Drug: AMG 404

Part 1b: Dose Exploration

EXPERIMENTAL

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Drug: AMG 994; Drug: AMG 404

Part 1c: Dose Exploration

EXPERIMENTAL

Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404.

Drug: AMG 994; Drug: AMG 404

Part 2: Dose Expansion

EXPERIMENTAL

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; Drug: AMG 404

Interventions

AMG 994 DRUG

Administered as an intravenous (IV) infusion.

Part 1a: Dose Exploration; Part 1b: Dose Exploration; Part 1c: Dose Exploration; Part 2: Dose Expansion

AMG 404 DRUG

Administered as an intravenous (IV) infusion.

Part 1a: Dose Exploration; Part 1b: Dose Exploration; Part 1c: Dose Exploration; Part 2: Dose Expansion

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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):

You may not qualify if:

• 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

Sponsors & Collaborators

• Amgen: lead

Study Sites (17)

City of Hope National Medical Center

Duarte, California, 91010, United States

Location

Henry Ford Hospital, Henry Ford Health Systems

Detroit, Michigan, 48202, United States

Location

University Hospitals Cleveland Medical Center

Cleveland, Ohio, 44106, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Monash Medical Centre

Clayton, Victoria, 3168, Australia

Location

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Centre Leon Berard

Lyon, 69008, France

Location

Universitatsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, 97078, Germany

Location

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

Location

National Hospital Organization Shikoku Cancer Center

Matsuyama, Ehime, 791-0280, Japan

Location

Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy

Warsaw, 02-781, Poland

Location

Hospital Universitari Vall d Hebron

Barcelona, Catalonia, 08035, Spain

Location

University College London Hospital

London, W1T 7HA, United Kingdom

Location

Related Links

• AmgenTrials clinical trials website

Limitations and Caveats

The study was planned to be conducted in 2 parts: part 1 (dose exploration) and part 2 (dose expansion); however, no participants enrolled beyond Cohort 2 due to a business decision to discontinue development of AMG 994. This decision was unrelated to the safety or efficacy.

Results Point of Contact

• Title: Study Director
• Organization: Amgen Inc.

medinfo@amgen.com

866-572-6436

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 27, 2021
• Study Start: April 29, 2021
• Primary Completion: June 5, 2023
• Study Completion: June 5, 2023
• Last Updated: January 6, 2025
• Results First Posted: January 6, 2025

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, 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.

Locations

US (5); FR (1); AU (2); ES (1); GB (1); DE (2); JP (2); PL (1); BE (1); CA (1)