Advanced Solid TumorsPhase 1NCT04362748
Study of AMG 256 in Adult Subjects With Advanced Solid Tumors
A Phase 1 study testing AMG 256 in people with Advanced Solid Tumors, run by Amgen at 11 sites in 4 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Advanced Solid Tumors
- What is being tested?
- AMG 256
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 11 sitesin 4 countries
- Study dates
- 15 Sep 2020to 21 Sep 2023
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
11 sites in 4 countries.
11 sites in 4 countries
United States4 sites
City of Hope National Medical Center
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Indiana University
Indianapolis, Indiana, 46202
Washington University
St Louis, Missouri, 63110
Australia3 sites
Chris OBrien Lifehouse
Camperdown, New South Wales, 2050
Monash Medical Centre
Clayton, Victoria, 3168
St Vincents Hospital Sydney
Darlinghurst, New South Wales, 2010
Belgium2 sites
Cliniques Universitaires Saint Luc
Brussels, 1200
Universitair Ziekenhuis Gent
Ghent, 9000
Spain2 sites
Hospital Universitari Vall d Hebron
Barcelona, Catalonia, 08035
Hospital Clinic i Provincial de Barcelona
Barcelona, Catalonia, 08036
About this study
Official title: A Phase 1 Study to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of AMG 256 in Patients With Advanced Solid Tumors
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).
- Conditions
- Advanced Solid Tumors
- Being tested
- AMG 256
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 256Drug
AMG 256 administered as an intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| Dose Escalation Phase | Experimental | Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose RP2D of AMG 256. Receives: Drug: AMG 256 |
| Dose Expansion Phase: Group 1 | Experimental | Participants will be administered with the MTD or RP2D of AMG 256 identified in the dose escalation part of the study. Receives: Drug: AMG 256 |
| Dose Expansion Phase: Group 2 | Experimental | Participants will be administered with the MTD or RP2D of AMG 256 identified in the dose escalation part of the study. Receives: Drug: AMG 256 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
The following toxicities graded using the Common Terminology Criteria for Adverse Events (CTCAE) that happened in the first 28 days after the first administration of AMG 256 were classified as DLTs:
- Any treatment related grade 5 toxicity.
- Grade 4 neutropenia or thrombocytopenia.
- Febrile neutropenia.
- Grade 4 anemia.
- Grade 3 or 4 non-hematologic toxicity, except: Grade 3 endocrinopathies, grade 3 nausea/vomiting or diarrhea, grade 3 fatigue < 1 week, asymptomatic ≥ grade 3 electrolyte abnormalities, ≥ grade 3 amylase or lipase, and other laboratory parameters of ≥ 3, not considered clinically relevant, and improved to grade ≤ 2 within 72 hours.
- Recurrent grade 2 pneumonitis.
- Delay in cycle 2 treatment for > 14 days due to an adverse event in the dose escalation portion of the trial due to trial drug-related toxicity.
- Any other toxicity requiring permanent discontinuation of AMG 256.
Measured: Day 1 to Day 28
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
An AE was any untoward medical occurrence in a clinical trial participant irrespective of a causal relationship with the study treatment. An AE could be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of a treatment. A TEAE was any AE that started on or after the first dose of IP and up to including 30 days after the last dose of IP or the end of trial date. A treatment-related AE was any TEAE that per investigator review had a reasonable possibility of being caused by the investigational product. Serious AEs (SAEs) included outcomes such as death, life-threatening situations, hospitalization or an extended hospital stay, significant incapacity, congenital defects, or other medically important events.
Measured: From 1st dose of AMG 256 untillast dose + 30 days or end of trial; median (min, max) trial duration was 3.7 (0.6, 23.6) months
Secondary outcomes (14)
Cohorts 1 to 9: Maximum Observed Plasma Concentration (Cmax) of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 22
Cohorts 1a and 2a: Cmax of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 15
Cohorts 1 to 9: Time to Reach Cmax (Tmax) of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 22
Cohorts 1a and 2a: Tmax of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 15
Cohorts 1 to 9: Area Under the Time Curve From Time 0 to 168 Hours Post-dose (AUC168) of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 22
Cohorts 1a and 2a: AUC168 of AMG 256
Blood samples of approximately 5 mL were collected for measurement of serum concentrations of AMG 256, estimated using non-compartmental methods.
Measured: Day 1 and Day 15
Objective Response Rate (ORR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
ORR is defined as the percentage of participants with a best overall response (BOR) of complete response (CR) or partial response (PR) per modified RECIST 1.1. Disappearance of all target lesions, non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR) is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Non target lesions must be non-Progressive Disease (non-PD). 95% confidence intervals (CI) for proportions are based on Clopper Pearson Method.
Measured: From 1st dose until min (last dose + 30 days, end of trial); Median (min, max) duration was 3.7 (0.6, 23.6) months
Immune ORR (iORR) Per Modified Immune Response Evaluation Criteria in Solid Tumors (iRECIST)
iORR per iRECIST is defined as the percentage of participants with confirmed BOR per iRECIST (iBOR) of immune CR (iCR) or immune PR (iPR). iBOR is the best time point response recorded from the start of the trial treatment until the end of treatment, taking into account any requirement for confirmation. iCR is the disappearance of all target lesions, non-target lesions and normalization of tumor markers. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. iPR is defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the re-treatment baseline sum diameters. 95% CI for proportions are based on Clopper Pearson Method.
Measured: From 1st dose until min (last dose + 30 days, end of trial); Median (min, max) duration was 3.7 (0.6, 23.6) months
Duration of Response (DOR) Per Modified RECIST v1.1
DOR is defined as time from first evidence of PR or CR until the first documentation ofdisease progression or death due to any cause;, whichever was earlier. DOR was derived for participants who had a confirmed PR or CR per RECIST 1.1. 95% CI is based on Kaplan-Meier method.
Measured: From 1st dose until min (last dose + 30 days, end of trial); Median (min, max) duration was 3.7 (0.6, 23.6) months
Progression-free Survival (PFS) Per Modified RECIST v1.1
PFS is defined as interval from the start of treatment to disease progression or death due to any cause (whichever came first). 95% CI is based on Kaplan-Meier method.
Measured: From enrollment until end of trial; Median (min, max) was 7.8 (0.6, 25.8) months
Disease Control Rate (DCR) Modified RECIST v1.1
DCR was defined as the percentange of participants with objective response or stable disease (SD) ≥ 16 weeks (from the first dosing date) as per modified RECIST 1.1.
Measured: From 1st study dose until min (last dose + 30 days, end of trial); Median (min, max) duration was 3.7 (0.6, 23.6) months
Duration of Stable Disease (DoSD) Per Modified RECIST v1.1
DoSD was defined as time from first IP until the first documentation of disease progression or death due to any cause, whichever occurred first. DoSD was calculated only in participants with best overall response of stable disease (SD).
Measured: From 1st dose of AMG 256 to end of trial (EOT); median trial duration (min, max) was 7.8 (0.6, 25.8) months
Overall Survival (OS)
OS was defined as the time from the start of treatment until eventt of death due to any cause.
Measured: From 1st dose of AMG 256 to end of trial (EOT); median trial duration (min, max) was 7.8 (0.6, 25.8) months
Number of Participants With Anti-AMG 256 Antibodies
Immunogenicity samples were collected the day of dosing, (within 60 minutes prior to the AMG 256 infusion) for the measurement of anti-AMG 256 binding antibodies at baseline and during post-baseline visits.
Measured: Cyle 1: Day 1, 8, 15 and 22; Cycle 2: Day 1 and 15; Cycle 3: Day 1; End of treatment (EOT) (2 years)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2020
- Study start15 Sep 2020
- Primary completion21 Sep 2023
- Study completion21 Sep 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Solid TumorsStudies of the same condition, open and under way.
- More trials run by AmgenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amgen
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- MD, Study director, Amgen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04362748
- Sponsor's protocol ID
- 20180144
- Status last verified
- Jul 2026
- First submitted
- 23 Apr 2020
- Last updated
- 23 Oct 2026
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
Publications
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.
PubMed 38343535