Clinical trial NCT05800964: Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors
Official title: Phase 1 First-In-Human Study to Explore the Safety, Tolerability, and Pharmacokinetics of AMG 305 in Subjects With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Advanced Solid Tumors
Keywords: Safety
Tolerability
Pharmacokinetics
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2023-04-06
Enrollment: 220
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to:

* Evaluate the safety and tolerability of AMG 305 in adult participants
* Determine the optimal biologically active dose (OBD), at or below the maximum tolerated dose (MTD) with MTD 1 as the maximum tolerated starting dose and MTD 2 as the maximum tolerated target dose
* Determine the recommended phase 2 dose (RP2D)


Eligibility criteria: Key Inclusion Criteria:

* Participant has provided informed consent to the main study prior to initiation of any study specific activities/procedures
* Male or female participants age ≥ 18 years
* Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
* Participants with histologically or cytologically documented selected solid tumor diseases. Participants must have exhausted available standard of care (SOC) systemic therapy or must not be candidates for such available therapy
* For dose expansion cohorts: participants with at least 1 measurable lesion ≥10 mm which has not undergone biopsy within 3 months of screening scan. This lesion cannot be biopsied at any time during the study
* Life expectancy \> 3 months
* Adequate organ function

Key Exclusion Criteria:

* Untreated central nervous system (CNS) metastases, leptomeningeal disease, or spinal cord compression
* History of other malignancy within the past 2 years
* Ongoing or active infection (including chronic or localized)
* Any pleural effusion or pericardial effusion within 4 weeks or ascites requiring recurrent drainage procedures or other medical intervention within 2 weeks prior to the first dose of the investigational products.
* Known interstitial lung disease
* Positive test for human immunodeficiency virus (HIV)
* Positive hepatitis B surface antigen or positive hepatitis C virus ribonucleic acid (RNA) by polymerase chain reaction (PCR)
* History of non-infectious/immune-checkpoint inhibitor related pneumonitis that required corticosteroids, or current or suspected pneumonitis that cannot be ruled out by imaging at screening.
* Anticancer therapies including radiotherapy (with the exception of palliative radiation) chemotherapy or molecularly targeted treatments or tyrosine kinase inhibitors (TKI) within 4 weeks of administration of the first dose of AMG 305; checkpoint inhibitor therapy within 3 months of the first dose of AMG 305; or other immunotherapies/monoclonal antibodies within 3 weeks of administration of the first dose of AMG 305.
* Has had a major surgery within 4 weeks of administration of a first dose of study treatment
* Autoimmune disorders requiring chronic systemic steroid therapy or any other form of immunosuppressive therapy while on study (eg, ulcerative colitis, Crohn's disease)
* Live and/or live-attenuated vaccines received within 28 days (or longer, if required locally) prior to the first dose of AMG 305
* Participants with unresolved toxicities from prior anti-tumor therapies to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1 or better, with the exception of alopecia and grade 2 peripheral neuropathy, which has been unchanged within the last 2 months and there is agreement to allow by both the investigator and sponsor
* Currently receiving treatment in another investigational device or drug study
* Female participants of childbearing potential or male participants unwilling to use protocol specified method of contraception
* Females who are pregnant, breastfeeding or who plan to breastfeed or become pregnant while on study
* 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

Primary outcomes:
measure: Percentage of Participants who Experience Dose Limiting Toxicities (DLTs)
timeFrame: Day 1 to Day 28
measure: Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Up to a maximum of 2 years
measure: Percentage of Participants who Experience Treatment-Related Adverse Events
timeFrame: Up to a maximum of 2 years
Secondary outcomes:
measure: Maximum Serum Concentration (Cmax) of AMG 305
timeFrame: Up to a maximum of 2 years
measure: Minimum Serum Concentration (Cmin) of AMG 305
timeFrame: Up to a maximum of 2 years
measure: Area Under the Concentration-Time Curve (AUC) of AMG 305
timeFrame: Up to a maximum of 2 years
measure: Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
timeFrame: Up to a maximum of 2 years
measure: ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
timeFrame: Up to a maximum of 2 years
measure: Duration of Response (DOR)
timeFrame: Up to a maximum of 2 years
measure: Time to Progression
timeFrame: Up to a maximum of 2 years
measure: Progression-Free Survival (PFS)
timeFrame: Up to a maximum of 2 years
measure: Overall Survival (OS) at 1 Year
timeFrame: 1 year
measure: OS at 2 Years
timeFrame: 2 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: New York
country: United States
facility: New York University Cancer Institute
state: New York
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: San Antonio
country: United States
facility: Next Oncology
state: Texas
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Toulouse cedex 9
country: France
facility: Institut Universitaire du Cancer Toulouse Oncopole
city: Villejuif
country: France
facility: Gustave Roussy
city: Dresden
country: Germany
facility: Universitaetsklinikum Dresden
city: Essen
country: Germany
facility: Universitaetsklinikum Essen
city: Wuerzburg
country: Germany
facility: Universitaetsklinikum Wuerzburg
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d Hebron
state: Cataluña
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
state: Cataluña
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: Manchester
country: United Kingdom
facility: Christie Hospital
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Sutton
country: United Kingdom
facility: Royal Marsden Hospital
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References: