Bladder Cancer, Esophageal Cancer, Locally Advanced or Metastatic Solid Tumor(s), Non-small Cell Lung Cancer (NSCLC), Prostate Cancer, Squamous Cell Carcinoma of Head and Neck (SCCHN), Triple Negative Breast Cancer (TNBC), Uterine Cancer
Conditions
Brief summary
The purpose of the trial is to evaluate the safety, determine the recommended Phase 2 dose (RP2D), and assess preliminary clinical activity of GEN1044 in patients with solid tumors.
Detailed description
The trial is an open-label, multi-center safety trial of GEN1044. The trial consists of two parts: a dose-escalation part (Phase 1) and an expansion part (Phase 2a). The expansion part of the trial will be initiated once the RP2D has been determined from Phase 1.
Interventions
BIOLOGICALGEN1044 is an immunoglobulin G1 (IgG1) bispecific antibody targeting CD3 and 5T4.
GEN1044 will be administered intravenously in cycles of 21 days.
Sponsors
AbbVie
Genmab
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: Dose-escalation part: • Patient with locally advanced or metastatic solid tumor(s) (excluding patients with primary central nervous system \[CNS\] tumors), who has experienced disease progression while on standard therapy or is intolerant of, or not eligible for, standard therapy. Expansion part: • Must have an advanced or metastatic, pathologically confirmed diagnosis of one of the following tumors: Uterine Cancer, Prostate Cancer, Esophageal Cancer, TNBC, SCCHN, NSCLC (both adenocarcinoma \[ACC\] and squamous cell carcinoma \[SCC\], Bladder Cancer. Both parts: * Must sign an informed consent form (ICF) indicating that he or she understands the purpose of, and procedures required for the trial, and is willing to participate in the trial prior to any trial related assessments or procedures. * Must have measurable disease according to response assessment criteria relevant to the tumor type. * Must have an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score of 0-1 at Screening and on C1D1. * A woman of reproductive potential must agree to use adequate contraception during the trial and for 4 months after the last GEN1044 administration. Adequate contraception is defined as highly effective methods of contraception. Key
Exclusion criteria
(both parts): 1. Has an uncontrolled intercurrent illness, including but not limited to: 1. Ongoing or active infection requiring intravenous treatment with anti-infective therapy 2. Symptomatic congestive heart failure (grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia. 3. Uncontrolled hypertension defined as systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg, despite optimal medical management. 4. Ongoing or recent evidence of significant autoimmune disease. Patients with a history of grade 3 or higher immune-related adverse events that led to treatment discontinuation. 5. Patients with a prior history of myositis, Guillain-Barré syndrome, or myasthenia gravis of any grade. 6. History of chronic liver disease or evidence of hepatic cirrhosis. 7. History of non-infectious pneumonitis that has required steroids, or currently has pneumonitis. 8. History of organ allograft (except for corneal transplant) or autologous or allogeneic bone marrow transplant, or stem cell rescue within 3 months prior to the first dose of GEN1044. 9. Serious, non-healing wound, skin ulcer (of any grade), or bone fracture. 2. Any history of intracerebral arteriovenous malformation, cerebral aneurysm, new or symptomatic brain metastases or stroke. 3. Prior therapy: Radiotherapy: Radiotherapy within 14 days prior to first GEN1044 administration. Palliative radiotherapy will be allowed. 4. Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1044 administration. Toxicities from previous anti-cancer therapies that have not resolved. 5. Has a history of ≥ grade 2 cytokine release syndrome (CRS) with other CD3-based bispecifics, or a history of ≥ grade 3 allergic reactions to monoclonal antibody therapy as well as known or has known allergies, hypersensitivity, or intolerance to GEN1044 or its excipients.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | From Day 1 to Day 21 of first cycle | The DLT was defined as Grade (G) \>= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for \>1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy's law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity. |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Day 1 through Day 263 (corresponding to maximum observed duration) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically significant'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received. |
| Number of Participants With Abnormal Laboratory Values | Day 1 through Day 263 (corresponding to maximum observed duration) | Number of participants with laboratory values of Grade \>= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology that is used for gradings (Grade 1-5) of Adverse Events (AEs) and of laboratory values; the latter being summarized here. This table reports laboratory values graded only on the numerical value of the reported parameter and is therefore not graded by symptoms or signs. The abnormal laboratory values assessed by the investigator as being AEs are reported also in the AE table. In case a participant reported multiple severity grades for a laboratory value, only the maximum grade was used. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Complete Response (CR) or Partial Response (PR) | Day 1 through Day 233 | The radiological evaluation based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) was performed by investigator using computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to \< 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions taking as reference the baseline sum of longest diameters. |
| Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug) | The detection and titer characterization of ADAs was performed using validated, specific, and sensitive electrochemiluminescence immunoassay (ECLIA) methods. Number of participants with ADA positive post baseline to GEN1044 are reported. |
Countries
Denmark, Israel, Spain, United States
Participant flow
Pre-assignment details
A total of 48 participants signed the informed consent form of whom 37 received study drug. The Safety Committee decided to stop enrollment during the dose-escalation part and therefore the expansion part of trial never started. Consequently, results are available for only the dose-escalation part.
Participants by arm
| Arm | Count |
|---|---|
| GEN1044 Doses 0.3/3/3 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (0.3 mg on C1D1 and 3 mg on C1D8 and C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 1 |
| GEN1044 Doses 1/3/10 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 10 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 4 |
| GEN1044 Doses 1/3/30 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 7 |
| GEN1044 Doses 1/5/30 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 7 |
| GEN1044 Doses 1/10/30 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 10 mg on C1D8, and 30 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 6 |
| GEN1044 Doses 1/5/37.5 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 37.5 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 2 |
| GEN1044 Doses 1/5/45 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 5 mg on C1D8, and 45 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 4 |
| GEN1044 Doses 1/3/60 mg Participants with locally advanced or metastatic non-CNS solid tumor(s) received an IV infusion of GEN1044 weekly (1 mg on C1D1, 3 mg on C1D8, and 60 mg on C1D15) for the first 4 cycles (each cycle was 21 days), followed by Q3W until the end of treatment. | 6 |
| Total | 37 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 2 | 3 | 0 | 3 | 0 | 1 | 2 |
| Overall Study | Other | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Sponsor decision | 0 | 2 | 3 | 7 | 2 | 2 | 3 | 4 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | GEN1044 Doses 0.3/3/3 mg | GEN1044 Doses 1/3/10 mg | GEN1044 Doses 1/3/30 mg | GEN1044 Doses 1/5/30 mg | GEN1044 Doses 1/10/30 mg | GEN1044 Doses 1/5/37.5 mg | GEN1044 Doses 1/5/45 mg | GEN1044 Doses 1/3/60 mg | Total |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 51.0 Years | 61.3 Years STANDARD_DEVIATION 12.89 | 60.4 Years STANDARD_DEVIATION 11.21 | 59.3 Years STANDARD_DEVIATION 8.18 | 62.3 Years STANDARD_DEVIATION 5.79 | 52.0 Years STANDARD_DEVIATION 8.49 | 55.8 Years STANDARD_DEVIATION 15.71 | 54.2 Years STANDARD_DEVIATION 15.29 | 58.4 Years STANDARD_DEVIATION 10.85 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 0 Participants | 2 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 11 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 4 Participants | 5 Participants | 2 Participants | 5 Participants | 2 Participants | 4 Participants | 4 Participants | 26 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) 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 (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 4 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 6 Participants | 5 Participants | 6 Participants | 2 Participants | 4 Participants | 5 Participants | 33 Participants |
| Sex: Female, Male Female | 1 Participants | 2 Participants | 3 Participants | 3 Participants | 4 Participants | 1 Participants | 2 Participants | 3 Participants | 19 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 4 Participants | 4 Participants | 2 Participants | 1 Participants | 2 Participants | 3 Participants | 18 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 |
|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 1 | 2 / 4 | 3 / 7 | 0 / 7 | 4 / 6 | 0 / 2 | 1 / 4 | 2 / 6 |
| other Total, other adverse events | 1 / 1 | 4 / 4 | 7 / 7 | 7 / 7 | 6 / 6 | 2 / 2 | 4 / 4 | 5 / 6 |
| serious Total, serious adverse events | 1 / 1 | 1 / 4 | 3 / 7 | 5 / 7 | 4 / 6 | 1 / 2 | 3 / 4 | 5 / 6 |
Outcome results
Primary
Number of Participants With Abnormal Laboratory Values
Number of participants with laboratory values of Grade \>= 3 by NCI-CTCAE v5.0 are reported. The NCI-CTCAE is a descriptive terminology that is used for gradings (Grade 1-5) of Adverse Events (AEs) and of laboratory values; the latter being summarized here. This table reports laboratory values graded only on the numerical value of the reported parameter and is therefore not graded by symptoms or signs. The abnormal laboratory values assessed by the investigator as being AEs are reported also in the AE table. In case a participant reported multiple severity grades for a laboratory value, only the maximum grade was used.
Time frame: Day 1 through Day 263 (corresponding to maximum observed duration)
Population: Safety set included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 1 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 1 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 1 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 4 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 1 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 1 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 7 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 1 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 1 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 4 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 1 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 5 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 1 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 1 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 2 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 1 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 1 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 2 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 2 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 2 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 1 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Hypoalbuminemia | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Hypokalemia | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Platelet count decreased | 1 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Hypermagnesemia | 1 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Anemia | 1 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Creatinine increased | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Hypomagnesemia | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Serum amylase increased | 1 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Lipase increased | 2 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Lymphocyte count decreased | 6 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Gamma-glutamyl transferase increased | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Abnormal Laboratory Values | Blood bilirubin increased | 0 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
The DLT was defined as Grade (G) \>= 3 cytokine release syndrome or immune effector cell-associated neurotoxicity syndrome; any G3 or 4 hematologic and non-hematologic toxicity (with exceptions defined by the protocol); laboratory abnormality that required clinically significant medical intervention, led to hospitalization, persisted for \>1 week, or resulted in a drug-induced liver injury; G3 or 4 febrile neutropenia; liver toxicity defined by Hy's law; any treatment-related toxicity that caused treatment discontinuation during Cycle 1; or any G5 toxicity.
Time frame: From Day 1 to Day 21 of first cycle
Population: Dose-determining set (DDS) included all participants who received at least 1 dose of study drug during the dose-escalation part, and who met the minimum exposure criterion and had sufficient safety evaluations or experienced a DLT during the first 21 days of dosing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Dose Limiting Toxicities (DLTs) | 3 Participants |
Primary
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An serious adverse event (SAE) is defined as an AE that meets one of the following criteria: fatal or life-threatening; results in persistent or significant disability/incapacity; constitutes a congenital anomaly/birth defect; medically significant (an event that jeopardizes the participant or may require medical or surgical intervention to prevent one of the outcomes listed above \[medical and scientific judgment must be exercised in deciding whether an AE is 'medically significant'\]); required inpatient hospitalization or prolongation of existing hospitalization. A TEAE is defined as an AE occurring or worsening between the first dose of GEN1044 and 30 days after the last dose received.
Time frame: Day 1 through Day 263 (corresponding to maximum observed duration)
Population: Safety set included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 1 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 4 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 7 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 3 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 7 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 5 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 6 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 4 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 2 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 1 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 3 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 4 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TEAE | 6 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) | Any TESAE | 5 Participants |
Secondary
Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044
The detection and titer characterization of ADAs was performed using validated, specific, and sensitive electrochemiluminescence immunoassay (ECLIA) methods. Number of participants with ADA positive post baseline to GEN1044 are reported.
Time frame: Day 1 through Day 263 (predose on Day 1 of Cycles 1, 2, 3, 5, 7, and then on Day 1 of every 4 cycles thereafter, end of treatment [EOT], and 30 days after last study drug)
Population: Immunogenicity analysis set included all participants who received at least 1 dose of study drug and had evaluable immunogenicity samples.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 3 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 2 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 1 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 1 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Antidrug Antibodies (ADAs) Positive to GEN1044 | 1 Participants |
Secondary
Number of Participants With Complete Response (CR) or Partial Response (PR)
The radiological evaluation based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) was performed by investigator using computed tomography (CT) scan/ magnetic resonance imaging (MRI) scan/ positron emission tomography (PET) scan. The CR was defined as disappearance of all target and non-target lesions and all pathological lymph nodes must have decreased to \< 10 mm in short axis. The PR was defined as at least a 30% decrease in the sum of the longest diameters of target lesions taking as reference the baseline sum of longest diameters.
Time frame: Day 1 through Day 233
Population: Full analysis set included all participants who received at least 1 dose of study drug. Participants were classified according to the assigned dose level cohort.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 0.3/3/3 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/3/10 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/3/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/5/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/10/30 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/5/37.5 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 0 Participants |
| GEN1044 Doses 1/5/45 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Complete response | 0 Participants |
| GEN1044 Doses 1/3/60 mg | Number of Participants With Complete Response (CR) or Partial Response (PR) | Partial response | 1 Participants |