Clinical trial NCT04362748: Study of AMG 256 in Adult Subjects With Advanced Solid Tumors
Official title: A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 256 in Patients With Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Advanced Solid Tumors
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2020-04-27
Enrollment: 34
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: To evaluate the safety and tolerability of AMG 256 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).


Eligibility criteria: Inclusion Criteria:

* Participant has provided informed consent 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 not amenable to curative treatment with surgery or radiation for which:
* No standard therapy exists, or
* Standard therapy has failed, not available, or
* In the investigator's opinion, standard therapy does not result in meaningful clinical benefit.
* 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.

Exclusion Criteria:

* Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal disease.
* History of other malignancy within the past 2 years, with the following Exceptions:
* Malignancy treated with curative intent and with no known active disease present for ≥ 2 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.
* History of solid organ transplantation.
* Major surgery within 28 days of study day 1.
* Live vaccine therapy within 4 weeks prior to study day 1.
* Currently receiving treatment in another investigational device or drug study, or less than 28 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
* Active infection requiring oral or intravenous therapy.
* 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.
* History of severe allergic reactions or severe acute hypersensitivity reaction.
* Female participant is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 3 months after the last dose of AMG 256.
* Female participants of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 3 months after the last dose of AMG 256.
* Female participants of childbearing potential with a positive pregnancy test assessed within 48 hours prior to day 1 of treatment 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 5 months after the last dose of AMG 256.
* Male participants with a pregnant partner who are unwilling to practice abstinence or use a condom during treatment and for an additional 5 months after the last dose of AMG 256.
* Male participants unwilling to abstain from donating sperm during treatment and for an additional 5 months after the last dose of AMG 256.
* 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 that, in the opinion of the investigator or Amgen physician, if consulted, would pose a risk to participants safety or interfere with the study evaluation, procedures or completion.

Primary outcomes:
measure: Number of Participants with Dose Limiting Toxicities (DLTs)
timeFrame: 28 days
measure: Number of Participants with Treatment-emergent Adverse Events (TEAEs)
timeFrame: Up to 2.5 Years
measure: Number of Participants with Treatment-Related Adverse Events
timeFrame: Up to 2.5 Years
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Vital Sign Measurement
timeFrame: Up to 2 Years
measure: Number of Participants Who Experience a Clinically Significant Change from Baseline in Clinical Laboratory Tests
timeFrame: Up to 2 Years
measure: Maximum Tolerated Dose (MTD) of AMG 256
timeFrame: 28 days
measure: Recommended Phase 2 Dose (RP2D) of AMG 256
timeFrame: 28 days
Secondary outcomes:
measure: Maximum Observed Plasma Concentration (Cmax) of AMG 256
timeFrame: Up to 2.5 Years
measure: Time to Achieve Cmax (Tmax) of AMG 256
timeFrame: Up to 2.5 Years
measure: Area Under the Plasma Concentration-time Curve (AUC) of AMG 256
timeFrame: Up to 2.5 Years
measure: Objective Response (OR)
timeFrame: Up to 2.5 Years
measure: Duration of Response (DOR)
timeFrame: Up to 2.5 Years
measure: Progression-Free Survival (PFS)
timeFrame: Up to 1 Year
measure: Disease Control Rate (DCR)
timeFrame: Up to 2.5 Years
measure: Duration of Stable Disease
timeFrame: Up to 2.5 Years
measure: Overall Survival (OS)
timeFrame: Up to 2 Years
measure: Number of Participants with anti-AMG 256 Antibodies
timeFrame: Up to 2.5 Years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Camperdown
country: Australia
facility: Chris OBrien Lifehouse
state: New South Wales
city: Darlinghurst
country: Australia
facility: St Vincents Hospital Sydney
state: New South Wales
city: Clayton
country: Australia
facility: Monash Medical Centre
state: Victoria
city: Bruxelles
country: Belgium
facility: Cliniques Universitaires Saint Luc
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
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
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
References:
citation: Kroenke MA, Starcevic Manning M, Zuch de Zafra CL, Zhang X, Cook KD, Archer M, Lolkema MP, Wang J, Hoofring S, Saini G, Aeffner F, Ahern E, Cabanas EG, Govindan R, Hui M, Gupta S, Mytych DT. Translatability of findings from cynomolgus monkey to human suggests a mechanistic role for IL-21 in promoting immunogenicity to an anti-PD-1/IL-21 mutein fusion protein. Front Immunol. 2024 Jan 26;15:1345473. doi: 10.3389/fimmu.2024.1345473. eCollection 2024.