Advanced Solid Tumors
Conditions
Keywords
Safety, Tolerability, Pharmacokinetics
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)
Interventions
DRUGAMG 305
Short-term intravenous (IV) infusion
Sponsors
Amgen
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants who Experience Dose Limiting Toxicities (DLTs) | Day 1 to Day 28 | — |
| Percentage of Participants who Experience Treatment-Emergent Adverse Events (TEAEs) | Up to a maximum of 2 years | Adverse events (AEs) are defined as any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. TEAEs are any event that occurs after the participant has received study treatment. Any clinically significant changes in vital signs, electrocardiograms (ECGs), and clinical laboratory tests, as assessed by the investigator, will also be reported as TEAEs. |
| Percentage of Participants who Experience Treatment-Related Adverse Events | Up to a maximum of 2 years | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum Serum Concentration (Cmax) of AMG 305 | Up to a maximum of 2 years | — |
| Minimum Serum Concentration (Cmin) of AMG 305 | Up to a maximum of 2 years | — |
| Area Under the Concentration-Time Curve (AUC) of AMG 305 | Up to a maximum of 2 years | — |
| Objective Response Rate (ORR) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) | Up to a maximum of 2 years | ORR is defined as best overall response (BOR) of complete response (CR) or partial response (PR), Clinical Benefit Rate (defined as BOR of CR, PR, or stable disease \[SD\] with duration of 24 weeks or longer) based on RECIST v1.1. |
| ORR based on Immune Response Evaluation Criteria in Solid Tumors (iRECIST) | Up to a maximum of 2 years | ORR is defined as immune best overall response (iBOR) of immune complete response (iCR) or immune partial response (iPR), Clinical Benefit Rate (defined as iBOR of iCR, iPR, or immune stable disease \[iSD\] with duration of 24 weeks or longer) based on iRECIST. |
| Duration of Response (DOR) | Up to a maximum of 2 years | DOR is defined as the time from the first documentation of objective response until the first documentation of disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST. |
| Time to Progression | Up to a maximum of 2 years | Time to progression is defined as the time rom first AMG 305 dose until the first documentation of radiological disease progression by RECIST v1.1 and iRECIST. |
| Progression-Free Survival (PFS) | Up to a maximum of 2 years | PFS is defined as the time from first AMG 305 dose until the first documentation of radiologic disease progression or death due to any cause, whichever occurs first) by RECIST v1.1 and iRECIST. |
| Overall Survival (OS) at 1 Year | 1 year | — |
| OS at 2 Years | 2 years | — |
Countries
Australia, Canada, France, Germany, Japan, South Korea, Spain, United Kingdom, United States
Contacts
STUDY_DIRECTORMD
Amgen
Outcome results
None listed