Advanced Solid TumorsPhase 1NCT04727554
Study of AMG 994 Monotherapy and AMG 994 and AMG 404 Combination Therapy in Participants With Advanced Solid Tumors
A Phase 1 study testing AMG 994 and AMG 404 in people with Advanced Solid Tumors, run by Amgen at 17 sites in 10 countries.
Trial 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. 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 994 and AMG 404
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 17 sitesin 10 countries
- Study dates
- 29 Apr 2021to 5 Jun 2023
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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/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.
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- 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):
- Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
- Platelet count ≥ 75 x 109/L
- Hemoglobin ≥ 9 g/dL
- Adequate renal laboratory assessments, as follows:
- Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation ≥ 45 mL/min/1.73 m2
- Hepatic function, as follows:
- Total bilirubin (TBL) ≤ 1.5 x upper limit of normal (ULN) or ≤ 3 x ULN for participants with liver metastasis
- Aspartate transaminase (AST) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis
- Alanine aminotransferase (ALT) ≤ 3 x ULN or ≤ 5 x ULN for participants with liver metastasis
- Alkaline phosphatase ≤ 2.5 x ULN or ≤ 5 x ULN for participants with liver metastasis
Who cannot join
- 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.
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- 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
- Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 21 days prior to study day 1.
- Treatment with a checkpoint inhibitor within 9 weeks prior to study day 1.
- Live vaccine therapy within 4 weeks prior to study drug administration.
- Current treatment or within 14 days of day 1 with immunosuppressive corticosteroid defined as > 10 mg prednisone daily or equivalent. Steroids with no minimal systemic effect (such as topical or inhalation) are permitted.
- Prior/Concurrent Clinical Study Experience
- Currently receiving treatment in another investigational device or drug study, or less than 21 days prior to study day 1 since ending treatment on another investigational device or drug study(ies).
- Evidence of active or radiological sequelae of non-infectious pneumonitis.
- History of any immune-related colitis. Infectious colitis is allowed if evidence of adequate treatment and clinical recovery exists and at least 3 months interval observed since diagnosis of colitis.
- History of allergic reactions or acute hypersensitivity reaction to antibody therapies.
- Positive/non-negative test results for human immunodeficiency virus (HIV).
- Hepatitis B and C based on the following results:
- Positive for hepatitis B surface antigen (HBsAg) (indicative of chronic hepatitis B or recent acute hepatitis B)
- Negative HBsAG and positive for hepatitis B core antibody: hepatitis B virus DNA by polymerase chain reaction (PCR) is necessary. Detectable hepatitis B virus DNA suggests occult hepatitis B.
- Positive hepatitis C virus antibody (HCVAb): hepatitis C virus RNA by PCR is necessary. Detectable hepatitis C virus RNA suggests chronic hepatitis C.
- Active infection requiring oral or intravenous therapy.
- Active or history of any autoimmune disease or immunodeficiencies. Participants with diabetes Type 1, vitiligo, psoriasis, hypo- or hyper-thyroid disease not requiring immunosuppressive treatment are permitted.
- 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.
- Unresolved toxicities from prior anti-tumor therapy, defined as not having resolved to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1, or are stable and well controlled with minimal, local, or noninvasive intervention AND there is agreement to allow by both the investigator and the Amgen Medical Monitor.
- Any history of grade 3 or higher colitis, pneumonitis, or neurological toxicity OR
- Unresolved toxicities from prior checkpoint inhibitor therapy, defined as not having resolved to CTCAE v5.0 grade 1.
- Exception: - clinically stable hypothyroid status managed with hormone replacement therapy, is permitted
- Other Exclusions
- Female participant is pregnant or breastfeeding or planning to become pregnant or breastfeed during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
- Female participants of childbearing potential unwilling to use 1 highly effective method of contraception during treatment and for an additional 6 months after the last dose of AMG 994 and/or AMG 404.
- Female participants of childbearing potential with a positive pregnancy test assessed at day 1 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 8 months after the last dose of AMG 994 and/or AMG 404.
- Male participants unwilling to abstain from donating sperm during treatment and for an additional 8 months after the last dose of AMG 994 and/or AMG 404.
- 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 (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.
Trial locations and contacts
17 sites in 10 countries.
17 sites in 10 countries
United States5 sites
University Hospitals Cleveland Medical Center
Cleveland, Ohio, 44106
Henry Ford Hospital, Henry Ford Health Systems
Detroit, Michigan, 48202
City of Hope National Medical Center
Duarte, California, 91010
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Australia2 sites
Monash Medical Centre
Clayton, Victoria, 3168
Linear Clinical Research Limited
Nedlands, Western Australia, 6009
Germany2 sites
Universitatsklinikum Ulm
Ulm, 89081
Universitätsklinikum Würzburg
Würzburg, 97078
Japan2 sites
National Cancer Center Hospital East
Kashiwa-shi, Chiba, 277-8577
National Hospital Organization Shikoku Cancer Center
Matsuyama, Ehime, 791-0280
Poland1 site
Narodowy Instytut Onkologii im Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy
Warsaw, 02-781
United Kingdom1 site
University College London Hospital
London, W1T 7HA
About this study
Official title: A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors
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.
Read the detailed description
AMG 994 will be administered by short term intravenous (IV) infusion once weekly in each 28-day cycle and AMG 404 will be administered by short-term IV infusion once every 4 weeks (Q4W) in a 28 day cycle (on day 1 of cycle 2 and beyond). The study will be conducted in 2 parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.
- Conditions
- Advanced Solid Tumors
- Being tested
- AMG 994, AMG 404
- Keywords
- Mesothelin expression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AMG 994Drug
Administered as an intravenous (IV) infusion.
AMG 404Drug
Administered as an intravenous (IV) infusion.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: AMG 994; Drug: AMG 404 |
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)
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
Measured: 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.
Measured: 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
OR was defined as achieving complete response (CR) or partial response (PR) per the modified RECIST 1.1 where CR is the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm and PR is at 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum of diameters.
Measured: Up to approximately 19.32 months
Duration of Response (DoR) Per Modified RECIST 1.1
DoR was defined as the number of months between first OR to disease progression or death (due to any cause), whichever occurs first. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.
Measured: Up to approximately 19.32 months
Overall Survival (OS) Per Modified RECIST 1.1
OS was defined as the time from initiation of AMG 994 until event of death due to any cause. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.
Measured: Up to approximately 19.32 months
Progression-free Survival Per Modified RECIST 1.1
PFS was defined as the time from initiation of AMG 994 until disease progression or death whichever occurs first. Death due to any cause counted as the event. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.
Measured: Up to approximately 19.32 months
Time to Progression (TTP) Per Modified RECIST 1.1
TTP was defined as time from initiation of AMG 994 until disease progression. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.
Measured: Up to approximately 19.32 months
Time to Subsequent Therapy
Time to subsequent therapy was defined as the time from initiation of AMG 994 until the first subsequent therapy. Median and 95% CI estimates of survival time were based on the Kaplan-Meier analysis.
Measured: Up to approximately 19.32 months
Maximum Serum Concentration (Cmax) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Time to Maximum Serum Concentration (Tmax) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Minimum Observed Serum Concentration (Cmin) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Area Under the Serum Concentration-time Curve During a Dosing Interval (AUCtau) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Terminal Half-life (t1/2) of AMG 994
Measured: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Cmax of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Tmax of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Cmin of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
AUClast of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
AUCtau of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
T1/2 of AMG 404
Measured: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2021
- Study start29 Apr 2021
- Primary completion5 Jun 2023
- Study completion5 Jun 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.
- 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
- 11 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
- NCT04727554
- Sponsor's protocol ID
- 20190136
- Status last verified
- Nov 2024
- First submitted
- 25 Jan 2021
- Last updated
- 6 Jan 2025
- 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.
Study at a glance
From the registry record, last updated by the sponsor on 6 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Multicenter, Open-label, Dose Exploration and Dose Expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics and Efficacy of AMG 994 Monotherapy and Combination of AMG 994 and AMG 404 in Subjects With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04727554
- Acronym / sponsor ID
- 20190136
- Conditions
- Advanced Solid Tumors
- Keywords
- Mesothelin expression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- AmgenIndustry (pharma, biotech, devices)
- Study start
- 29 Apr 2021 (actual)
- Primary completion
- 5 Jun 2023 (actual)
- Study completion
- 5 Jun 2023 (actual)
- First posted
- 27 Jan 2021 (actual)
- Results
- Posted 6 Jan 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
AMG 994 will be administered by short term intravenous (IV) infusion once weekly in each 28-day cycle and AMG 404 will be administered by short-term IV infusion once every 4 weeks (Q4W) in a 28 day cycle (on day 1 of cycle 2 and beyond). The study will be conducted in 2 parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Part 1a: Dose Exploration | Experimental | Drug: AMG 994, Drug: AMG 404Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404. |
| Part 1b: Dose Exploration | Experimental | Drug: AMG 994, Drug: AMG 404Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404. |
| Part 1c: Dose Exploration | Experimental | Drug: AMG 994, Drug: AMG 404Determine the maximum tolerated dose (MTD) or the recommended phase 2 dose (RP2D) of AMG 994, in combination with AMG 404. |
| Part 2: Dose Expansion | Experimental | Drug: AMG 994, Drug: AMG 404Participants 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. |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- 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:
- 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.
Key exclusion criteria (45 listed)
- 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]:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AMG 994Administered as an intravenous (IV) infusion. | Drug | Part 1a: Dose Exploration, Part 1b: Dose Exploration, Part 1c: Dose Exploration, Part 2: Dose Expansion |
| AMG 404Administered as an intravenous (IV) infusion. | Drug | Part 1a: Dose Exploration, Part 1b: Dose Exploration, Part 1c: Dose Exploration, Part 2: Dose Expansion |
Primary outcome
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Time frame: Up to Day 28 of Cycle 1 (one cycle = 28 days)
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
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
Time frame: 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.
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.
18 secondary outcomes
Objective Response (OR) Per Modified Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: Up to approximately 19.32 months
Duration of Response (DoR) Per Modified RECIST 1.1
Time frame: Up to approximately 19.32 months
Overall Survival (OS) Per Modified RECIST 1.1
Time frame: Up to approximately 19.32 months
Progression-free Survival Per Modified RECIST 1.1
Time frame: Up to approximately 19.32 months
Time to Progression (TTP) Per Modified RECIST 1.1
Time frame: Up to approximately 19.32 months
Time to Subsequent Therapy
Time frame: Up to approximately 19.32 months
Maximum Serum Concentration (Cmax) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Time to Maximum Serum Concentration (Tmax) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Minimum Observed Serum Concentration (Cmin) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Area Under the Serum Concentration-time Curve From Time Zero to Time of Last Quantifiable Concentration (AUClast) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Area Under the Serum Concentration-time Curve During a Dosing Interval (AUCtau) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Terminal Half-life (t1/2) of AMG 994
Time frame: Cycle 1 and 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose); Cycle 1, Day 22 (pre-dose, EOI, 6, and 12 hours post dose)
Cmax of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Tmax of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Cmin of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
AUClast of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
AUCtau of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
T1/2 of AMG 404
Time frame: Cycle 2, Day 1 (pre-dose, end of infusion [EOI], 2, 4.5, 6.5, and 12 hours post dose)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jan 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- AmgenTrials clinical trials websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MD study director
Amgen
17 sites in 10 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing AMG 994 and AMG 404 in people with Advanced Solid Tumors, run by Amgen at 17 sites in 10 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 25 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 17 sites in United States, Australia, Germany, Japan, Belgium and 5 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Jan 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) (time frame: Up to Day 28 of Cycle 1 (one cycle = 28 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jan 2025.