Advanced Solid Tumors
Conditions
Brief summary
To evaluate the safety and tolerability of AMG 404, a monoclonal antibody that binds to PD-1 and inhibits its engagement with ligands, in patients with advanced solid tumors.
Interventions
DRUGAMG 404
AMG 404 will be examined for safety, tolerability, PK, and PD of AMG 404 in subjects with advanced solid tumors.
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
* Subject has provided informed consent prior to initiation of any study specific activities/procedures. * Age greater than or equal to 18 years old at the time of signing informed consent. * Life expectancy of greater than 3 months, in the opinion of the investigator * Subject must have histologically or cytologically confirmed metastatic or locally advanced solid tumors not amenable to curative treatment with surgery or radiation. * Cohort 7: participant must have one of the following tumor types: melanoma, small cell lung cancer, NSCLC (PD-L1 positive), head and neck squamous cell cancer (PD-L1 positive), urothelial (PD-L1 positive), gastric or GEJ adenocarcinoma (PD-L1 positive), esophageal (squamous, PD-L1 positive), cervical (PD-L1 positive), hepatocellular carcinoma, merkel cell carcinoma, squamous cell carcinoma of the skin, renal cell carcinoma (clear cell) subtypes of sarcoma (undifferentiated pleiomorphic / malignant fibrous histiocytoma, poorly differentiated and/or dedifferentiated liposarcoma, alveolar soft tissue sarcoma, angiosarcoma), thymic carcinoma, nasopharyngeal carcinoma (EBV positive), mesothelioma * Cohort 8: participant must be MSI-H or MMR-deficient * Cohort 9: participant must have NSCLC, PD-L1 positive, TPS ≥ 50%; not have EGFR or ALK or ROS1 genomic tumor aberrations and may not have received prior systemic treatment for the advanced disease (prior neoadjuvant, adjuvant, or concurrent chemoradiation is allowed). * At least 1 measurable as defined by modified RECIST 1.1 which has not undergone biopsy within 3 months of the screening scan. This lesion cannot be biopsied at any time during the study. Note: if there is only one lesion available for biopsy and radiographic assessment, it may be permitted to be biopsied after discussion with sponsor. * Subjects 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 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 are deemed irreversible, 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. * Eastern Cooperative Oncology Group (ECOG) Performance Status of less than or equal to 2. * Hematologic function, as follows without growth factor support within 2 weeks prior to study day 1: Absolute neutrophil count (ANC) greater than or equal to 1.0 x 10E9/L; Platelet count greater than or equal to 75 x 10E9/L; Hemoglobin greater than or equal to 9 g/dL (90 g/L). * Adequate renal laboratory assessments, as follows: Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation . 60 ml/min/1.73 m\^2 for Cohorts 1, 2, and 4 Estimated glomerular filtration rate based on MDRD (Modification of Diet in Renal Disease) calculation \>= 45 ml/min/1.73 m\^2 for Cohorts 3, 6, 7, 8 and 9. * Hepatic function, as follows: Total bilirubin less than or equal to 1.5 x ULN or less than or equal to 3 x ULN for subjects with liver metastasis; AST less than or equal to 3 x ULN or less than or equal to' 5 x ULN for subjects with liver metastasis; ALT less than or equal to 3 x ULN or less than or equal to 5 x ULN for subjects with liver metastasis; Alkaline phosphatase less than or equal to 2.5 x ULN or less than or equal to 5 x ULN for subjects with liver metastasis (Note: elevated alkaline phosphatase is acceptable if it is due to non-hepatic associated pathology \[eg, bone disease\]). * Subjects enrolled to Cohorts 7-9 must submit tumor tissue sample. Fresh tumor biopsies may be performed if subject has a readily accessible tumor lesion and who consent to the biopsies. If fresh biopsies cannot be obtained, archival tumor samples are acceptable. Prior to enrollment it is required to determine that there is enough tumor tissue available to be sent to the central laboratory: Cohorts 7 and 9: Archival tissue collected up to 12 months prior to screening date is permitted. Biopsies collected between 12-18 months prior to screening are allowed upon discussion with the medical monitor. Subjects with EBV associated nasopharyngeal carcinoma may submit biopsy with EBV test results from within 36 months prior to screening; Cohort 8: Archival tissue with MSI-high/dMMR test results collected up to 36 months prior to screening is permitted.
Exclusion criteria
* Disease Related. Primary brain tumor, untreated or symptomatic brain metastases and leptomeningeal disease (exception: benign asymptomatic tumors are permitted). * 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 greater than or equal to 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. Other malignancies which do not require systemic therapy, may be considered upon discussion with the medical monitor. * History of solid organ transplantation. * Major surgery within 28 days of study day 1. * Prior/Concomitant Therapy: Prior treatment with anti-programmed death 1 (PD-1), anti-PD-L1, CTLA-4 or other checkpoint inhibitor drugs * Anti-tumor therapy (radiotherapy, chemotherapy, antibody therapy, molecular targeted therapy, or investigational agent) within 21 days prior to study day 1. Note: Palliative radiotherapy is permitted. * 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 greater than 10 mg prednisone daily or equivalent. Corticosteroids with no or minimal systemic effect (such as topical or inhalation) are permitted. Note: Corticosteroids \> 10 mg prednisone used for management of contrast allergy for study scans is allowed. * 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). * Diagnostic Assessments: Evidence of interstitial lung disease or active, 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 for Human Immunodeficiency Virus (HIV). * Has known active Hepatitis B (eg, hepatitis B antigen \[HBsAg\] reactive) or Hepatitis C (eg, HCV RNA \[qualitative\] is detected). * Subject currently has an active infection requiring systemic therapy. * Active or history of any autoimmune disease or immunodeficiencies. Subjects with Type I diabetes, 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 greater than class II), unstable angina, or cardiac arrhythmia requiring antiarrhythmic 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 non-invasive intervention AND there is agreement to allow by both the investigator and the Amgen Medical Monitor. * Other Exclusions: Males and females of reproductive potential who are unwilling to practice highly effective methods of birth control while on study through 6 months (females) and 8 months (males) after receiving the last dose of AMG 404.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | Up to Day 28 | Toxicities were graded with the Common Terminology Criteria for Adverse Events CTCAE v5.0., the following toxicities 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 * Recurrent grade 2 pneumonitis * Any other toxicity requiring permanent discontinuation of AMG 404. |
| Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Up to the last dose of AMG 404 + 140 days (approximately 46 months); median (min, max) exposure to AMG 404 was 3.58 (0.02, 41.7) months | A TEAE is any adverse event (AE) starting on or after the first administration of investigational product (IP) and up to and including 140 days after the last IP dose date or end of the study, whichever occurs earlier. A TEAE with unknown/missing relatedness to AMG 404 is assumed as an event is related to AMG 404. A serious adverse event (SAE) is defined as an adverse event that: is fatal, is life threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important serious event. A treatment-related AE (TRAE) is any TEAE that per investigator review has a reasonable possibility of being caused by the investigational product. In the unlikely event that the relationship is missing, the TEAE will be considered TRAE and documented in a footnote of the treatment-related summary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length) | Assessment of AMG 404 exposure over 28 days. |
| Number of Participants With Anti-AMG 404 Antibodies | Day 1 pre-dose and Day 15 | Transient was defined as the number of participants with negative result at the participant's last time point tested within the study period. Only participants with both baseline and post-baseline are included. |
| Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | Up to approximately 54 months | Objective response was defined as a tumor response assessment of either complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of the diameters of target lesions) measured by positron emission tomography(PET)/computed tomography (CT), CT or magnetic resonance imaging (MRI) and assessed per RECIST v1.1. Participants who did not experience PR/CR or did not have any follow-up tumor assessments was regarded as non-responders. This endpoint was determined only for participants with measurable disease at baseline. |
| AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length) | Maximum concentration of AMG 404 in blood serum at different time points. |
| Disease Control Rate (DCR) Per Modified RECIST v1.1 | Up to approximately 54 months | DCR was defined as the percentage of participants in whom objective response (CR or PR) or stable disease (SD) was determined as per RECIST v1.1. |
| Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | Up to approximately 54 months | DoSD was measured from the start of treatment until the first documentation of disease progression or death due to any cause. DoSD was calculated only in participants with the best overall response of SD, defined as neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for PD. KM analysis was used to estimate the median DoSD, and CIs were calculated using the Brookmeyer and Crowley method. DoSD was censored at the last evaluable post-baseline tumor assessment date or at the first dose of IP, if no progression or death was documented. |
| Progression-free Survival (PFS) Per Modified RECIST v1.1 | Up to approximately 48 months | PFS was defined as the time from the first dose of IP unite the first documentation of radiological disease progression or death due to any cause, whichever occurred first in the absence of subsequent anticancer therapy. |
| Duration of Response (DOR) Per Modified RECIST v1.1 | Up to approximately 43 months | DOR was defined as the time from the first documentation of objective response (CR or PR) until the first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who achieved objective response were evaluated for DOR. DOR was censored at the last evaluable post-baseline tumor assessment date; otherwise, at the first dose of IP. Kaplan-Meier (KM) analysis was used to estimate DOR for responders, providing a median value and 80% confidence intervals (CI) where sufficient data were available. The Brookmeyer and Crowley method was used to calculate confidence intervals. For cohorts with limited responders or heavily censored data, the median DOR or CI bounds could not be calculated. |
| AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length) | Tmax represents the time to reach Cmax in the blood serum. |
Countries
Australia, Belgium, Brazil, Canada, Japan, Poland, Singapore, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
This study was conducted at 34 centers in Australia, Belgium, Brazil, Canada, Japan, Poland, Singapore, South Korea, Spain, Taiwan, Turkey, the United Kingdom, and the United States. Participants were recruited between 05 March 2019 and 02 November 2023.
Pre-assignment details
Participants were screened for a period up to 28 days prior to Day 1, and then randomized to receive different doses of AMG 404. Cohort 5 was planned but it was never opened.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) Participants received AMG 404 Dose A administered as an IV injection. This cohort contributed to identifying the RP2D. | 3 |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) Participants received AMG 404 Dose B administered as an IV injection. This cohort contributed to identifying the RP2D. | 9 |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) Participants received AMG 404 Dose B administered as an IV injection. This cohort contributed to identifying the RP2D. | 21 |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) Participants received AMG 404 Dose C administered as an IV injection. This cohort contributed to identifying the RP2D. | 21 |
| Cohort 6: Dose Expansion AMG 404 RP2D Participants received AMG 404 at the RP2D (Dose B). | 20 |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy Participants affected by various types of specific tumors received AMG 404 at the RP2D (Dose B). | 42 |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy Participants affected by MSI-high and dMMR types of tumors received AMG 404 at the RP2D (Dose B). | 42 |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy Participants affected by PD-L1 positive non-small cell lung cancer with a TPS ≥ 50% received AMG 404 at the RP2D (Dose B). | 13 |
| Total | 171 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 2 | 5 | 8 | 10 | 3 | 20 | 10 | 5 |
| Overall Study | Decision by Sponsor | 0 | 0 | 1 | 0 | 1 | 1 | 10 | 2 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 1 | 3 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 2 | 1 | 4 | 5 | 3 |
Baseline characteristics
| Characteristic | Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Cohort 4: Dose Exploration AMG 404 Dose C (High) | Cohort 6: Dose Expansion AMG 404 RP2D | Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 59.3 years STANDARD_DEVIATION 10.7 | 62.1 years STANDARD_DEVIATION 9.8 | 59.3 years STANDARD_DEVIATION 14.5 | 58.8 years STANDARD_DEVIATION 12.6 | 60.1 years STANDARD_DEVIATION 8.7 | 59.5 years STANDARD_DEVIATION 14.5 | 62.5 years STANDARD_DEVIATION 11.8 | 64.6 years STANDARD_DEVIATION 9 | 60.7 years STANDARD_DEVIATION 12.3 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 7 Participants | 1 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 9 Participants | 20 Participants | 19 Participants | 19 Participants | 37 Participants | 35 Participants | 12 Participants | 152 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants | 0 Participants | 0 Participants | 6 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants | 0 Participants | 5 Participants | 4 Participants | 4 Participants | 8 Participants | 11 Participants | 9 Participants | 41 Participants |
| Race/Ethnicity, Customized Black (or African American) | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants | 1 Participants | 7 Participants |
| Race/Ethnicity, Customized Multiple | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 6 Participants | 0 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized White | 2 Participants | 9 Participants | 14 Participants | 14 Participants | 15 Participants | 28 Participants | 28 Participants | 3 Participants | 113 Participants |
| Sex: Female, Male Female | 1 Participants | 5 Participants | 10 Participants | 11 Participants | 10 Participants | 17 Participants | 23 Participants | 2 Participants | 79 Participants |
| Sex: Female, Male Male | 2 Participants | 4 Participants | 11 Participants | 10 Participants | 10 Participants | 25 Participants | 19 Participants | 11 Participants | 92 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 5 / 9 | 8 / 21 | 10 / 21 | 3 / 20 | 20 / 42 | 10 / 42 | 5 / 13 | 63 / 171 |
| other Total, other adverse events | 3 / 3 | 9 / 9 | 20 / 20 | 20 / 21 | 20 / 20 | 41 / 41 | 39 / 41 | 12 / 13 | 164 / 168 |
| serious Total, serious adverse events | 2 / 3 | 5 / 9 | 12 / 20 | 15 / 21 | 11 / 20 | 28 / 41 | 16 / 41 | 7 / 13 | 96 / 168 |
Outcome results
Primary
Number of Participants Who Experienced Dose Limiting Toxicities (DLTs)
Toxicities were graded with the Common Terminology Criteria for Adverse Events CTCAE v5.0., the following toxicities 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 * Recurrent grade 2 pneumonitis * Any other toxicity requiring permanent discontinuation of AMG 404.
Time frame: Up to Day 28
Population: The DLT analysis set included DLT evaluable participants who had completed the DLT window period of 28 days on AMG 404 treatment (starting cycle 1, day 1) or experienced a DLT any time during the DLT window or had received at least 90% of the planned dose of investigational product and was followed for at least 1 cycle. Only participants in cohort 1 to 4 were DLT-evaluable.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) | 0 Participants |
Primary
Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs)
A TEAE is any adverse event (AE) starting on or after the first administration of investigational product (IP) and up to and including 140 days after the last IP dose date or end of the study, whichever occurs earlier. A TEAE with unknown/missing relatedness to AMG 404 is assumed as an event is related to AMG 404. A serious adverse event (SAE) is defined as an adverse event that: is fatal, is life threatening, requires in-patient hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and other medically important serious event. A treatment-related AE (TRAE) is any TEAE that per investigator review has a reasonable possibility of being caused by the investigational product. In the unlikely event that the relationship is missing, the TEAE will be considered TRAE and documented in a footnote of the treatment-related summary.
Time frame: Up to the last dose of AMG 404 + 140 days (approximately 46 months); median (min, max) exposure to AMG 404 was 3.58 (0.02, 41.7) months
Population: The safety analysis set consisted of all participants who received at least one dose of AMG 404.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 3 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 1 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 2 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 1 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 5 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 4 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 9 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 5 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 20 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 8 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 3 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 12 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 21 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 8 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 15 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 15 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 13 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 11 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 2 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 20 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 34 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 28 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 15 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 41 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 26 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 40 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 16 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 7 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | Fatal AEs | 5 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | SAEs | 7 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | TRAEs | 8 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants Who Experienced Treatment-emergent Adverse Events (TEAEs) | All TEAEs | 13 Participants |
Secondary
AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2
Maximum concentration of AMG 404 in blood serum at different time points.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
Population: The PK Analysis Set contained all participants who received at least 1 dose of AMG 404 and had at least 1 PK sample collected. These participants were evaluated for PK analysis unless the number of data points required for analysis was not enough, or significant protocol deviations affected the data, or if key dosing or sampling information was missing. Per SAP, cohorts have been combined by dose for reporting of PK data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 1 | 84 µg/mL | Geometric Coefficient of Variation 38 |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 2 | 96 µg/mL | Geometric Coefficient of Variation 39 |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 1 | 176 µg/mL | Geometric Coefficient of Variation 23 |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 2 | 203 µg/mL | Geometric Coefficient of Variation 33 |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 1 | 398 µg/mL | Geometric Coefficient of Variation 24 |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 Pharmacokinetic (PK) Parameter by Dose Group: Maximum Observed Serum Concentration (Cmax) During Cycle 1 and 2 | Cycle 2 | 485 µg/mL | Geometric Coefficient of Variation 50 |
Secondary
AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2
Assessment of AMG 404 exposure over 28 days.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
Population: The PK Analysis Set contained all participants who received at least 1 dose of AMG 404 and had at least 1 PK sample collected. These participants were evaluated for PK analysis unless the number of data points required for analysis was not enough, or significant protocol deviations affected the data, or if key dosing or sampling information was missing. Per SAP, cohorts have been combined by dose for reporting of PK data
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 1 | 732 day*µg/mL | Geometric Coefficient of Variation 40 |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 2 | 1130 day*µg/mL | Geometric Coefficient of Variation 27 |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 1 | 1660 day*µg/mL | Geometric Coefficient of Variation 30 |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 2 | 2240 day*µg/mL | Geometric Coefficient of Variation 33 |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 1 | 3800 day*µg/mL | Geometric Coefficient of Variation 31 |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Area Under the Serum Concentration-time Curve From Day 0 to Day 28 (AUC0-28d) During Cycle 1 and 2 | Cycle 2 | 4730 day*µg/mL | Geometric Coefficient of Variation 49 |
Secondary
AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2
Tmax represents the time to reach Cmax in the blood serum.
Time frame: Day 1 pre-dose, end of infusion (EOI), 2h, 4h post dose; Day 2; Day 4; Day 8; Day 15 of Cycle 1 and 2 (28 day cycle length)
Population: The PK Analysis Set contained all participants who received at least 1 dose of AMG 404 and had at least 1 PK sample collected. These participants were evaluated for PK analysis unless the number of data points required for analysis was not enough, or significant protocol deviations affected the data, or if key dosing or sampling information was missing. Per SAP, cohorts have been combined by dose for reporting of PK data
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 1 | 0.550 Hour |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 2 | 2.53 Hour |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 1 | 0.783 Hour |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 2 | 0.742 Hour |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 1 | 2.50 Hour |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | AMG 404 PK Parameter by Dose Group: Time to Achieve Cmax (Tmax) During Cycle 1 and 2 | Cycle 2 | 0.883 Hour |
Secondary
Disease Control Rate (DCR) Per Modified RECIST v1.1
DCR was defined as the percentage of participants in whom objective response (CR or PR) or stable disease (SD) was determined as per RECIST v1.1.
Time frame: Up to approximately 54 months
Population: The safety analysis set consisted of all participants who received at least one dose of AMG 404.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 33.3 Percentage of participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 44.4 Percentage of participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 35.0 Percentage of participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 42.9 Percentage of participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 55.0 Percentage of participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 48.8 Percentage of participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 70.7 Percentage of participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Disease Control Rate (DCR) Per Modified RECIST v1.1 | 76.9 Percentage of participants |
Secondary
Duration of Response (DOR) Per Modified RECIST v1.1
DOR was defined as the time from the first documentation of objective response (CR or PR) until the first documentation of disease progression or death due to any cause, whichever occurred first. Only participants who achieved objective response were evaluated for DOR. DOR was censored at the last evaluable post-baseline tumor assessment date; otherwise, at the first dose of IP. Kaplan-Meier (KM) analysis was used to estimate DOR for responders, providing a median value and 80% confidence intervals (CI) where sufficient data were available. The Brookmeyer and Crowley method was used to calculate confidence intervals. For cohorts with limited responders or heavily censored data, the median DOR or CI bounds could not be calculated.
Time frame: Up to approximately 43 months
Population: The safety analysis set included all participants who received at least one dose of AMG 404. The DOR analysis was conducted for participants who achieved an objective response (CR or PR) as determined by modified RECIST 1.1 criteria. Participants who did not achieve an objective response were not included in the DOR analysis, as DOR could not be calculated for these cases.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Duration of Response (DOR) Per Modified RECIST v1.1 | NA Months |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Duration of Response (DOR) Per Modified RECIST v1.1 | 16.85 Months |
| Cohort 6: Dose Expansion AMG 404 RP2D | Duration of Response (DOR) Per Modified RECIST v1.1 | NA Months |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Duration of Response (DOR) Per Modified RECIST v1.1 | 11.07 Months |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Duration of Response (DOR) Per Modified RECIST v1.1 | NA Months |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Duration of Response (DOR) Per Modified RECIST v1.1 | NA Months |
Secondary
Duration of Stable Disease (DoSD) Per Modified RECIST v1.1
DoSD was measured from the start of treatment until the first documentation of disease progression or death due to any cause. DoSD was calculated only in participants with the best overall response of SD, defined as neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for PD. KM analysis was used to estimate the median DoSD, and CIs were calculated using the Brookmeyer and Crowley method. DoSD was censored at the last evaluable post-baseline tumor assessment date or at the first dose of IP, if no progression or death was documented.
Time frame: Up to approximately 54 months
Population: The analysis population consisted of participants who achieved a best overall response of SD per Modified RECIST v1.1 criteria. This analysis includes only participants from the safety analysis set who received at least one dose of AMG 404 and met the criteria for SD based on tumor assessments.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 5.36 Months |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 5.54 Months |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 6.54 Months |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 5.59 Months |
| Cohort 6: Dose Expansion AMG 404 RP2D | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 4.62 Months |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 5.55 Months |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 16.56 Months |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Duration of Stable Disease (DoSD) Per Modified RECIST v1.1 | 3.55 Months |
Secondary
Number of Participants With Anti-AMG 404 Antibodies
Transient was defined as the number of participants with negative result at the participant's last time point tested within the study period. Only participants with both baseline and post-baseline are included.
Time frame: Day 1 pre-dose and Day 15
Population: The safety analysis set consisted of all participants who received at least one dose of AMG 404.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants With Anti-AMG 404 Antibodies | Transient | 0 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 0 Participants |
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 0 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 1 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Transient | 1 Participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 1 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 1 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 4 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 3 Participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Number of Participants With Anti-AMG 404 Antibodies | Transient | 1 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants With Anti-AMG 404 Antibodies | Transient | 0 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 1 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 1 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 4 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants With Anti-AMG 404 Antibodies | Transient | 4 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 4 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Transient | 7 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 11 Participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 11 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 7 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 2 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Transient | 4 Participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 5 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Transient | 2 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive post-baseline and negative at baseline | 2 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at anytime | 2 Participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Number of Participants With Anti-AMG 404 Antibodies | Positive at or before baseline | 0 Participants |
Secondary
Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1
Objective response was defined as a tumor response assessment of either complete response (CR) (disappearance of all target lesions) or partial response (PR) (at least a 30% decrease in the sum of the diameters of target lesions) measured by positron emission tomography(PET)/computed tomography (CT), CT or magnetic resonance imaging (MRI) and assessed per RECIST v1.1. Participants who did not experience PR/CR or did not have any follow-up tumor assessments was regarded as non-responders. This endpoint was determined only for participants with measurable disease at baseline.
Time frame: Up to approximately 54 months
Population: The safety analysis set consisted of all participants who received at least one dose of AMG 404.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 0.0 Percentage of participants |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 0.0 Percentage of participants |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 5.0 Percentage of participants |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 4.8 Percentage of participants |
| Cohort 6: Dose Expansion AMG 404 RP2D | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 25.0 Percentage of participants |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 17.1 Percentage of participants |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 36.6 Percentage of participants |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Objective Tumor Response Per Evaluation Criteria in Solid Tumours (RECIST) V1.1 | 30.8 Percentage of participants |
Secondary
Progression-free Survival (PFS) Per Modified RECIST v1.1
PFS was defined as the time from the first dose of IP unite the first documentation of radiological disease progression or death due to any cause, whichever occurred first in the absence of subsequent anticancer therapy.
Time frame: Up to approximately 48 months
Population: The safety analysis set consisted of all participants who received at least one dose of AMG 404.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1: Dose Escalation AMG 404 Dose A (Low) | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 2.89 Months |
| Cohort 2: Dose Escalation AMG 404 Dose B (Mid) | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 1.84 Months |
| Cohort 3: Dose Expansion AMG 404 Dose B (Mid) | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 1.89 Months |
| Cohort 4: Dose Exploration AMG 404 Dose C (High) | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 1.84 Months |
| Cohort 6: Dose Expansion AMG 404 RP2D | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 3.68 Months |
| Cohort 7: AMG 404 RP2D Tumor Specific Efficacy | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 3.06 Months |
| Cohort 8: AMG 404 RP2D Tumor Specific Efficacy | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 16.56 Months |
| Cohort 9: AMG 404 RP2D Tumor Specific Efficacy | Progression-free Survival (PFS) Per Modified RECIST v1.1 | 4.37 Months |