Solid Tumor, Adult
Conditions
Keywords
Monoclonal antibody
Brief summary
The drug that will be investigated in the study is GEN1053. GEN1053 is an antibody designed to (re)activate and increase antitumor immunity. Since this is the first study of GEN1053 in humans, the main purpose is to evaluate safety. Besides safety, the study will determine the recommended GEN1053 dose to be tested in a larger group of participants and assess preliminary clinical activity of GEN1053. GEN1053 will be studied in a broad group of cancer patients, having different kinds of solid tumors. All participants will get GEN1053. The study consists of two parts: Part 1 tests increasing doses of GEN1053 (escalation), followed by Part 2 which tests the recommended phase 2 dose GEN1053 dose from Part 1 (expansion).
Detailed description
The trial is a First in Human open-label, multicenter, multinational safety trial in participants with non-central nervous system (non-CNS) metastatic or advanced malignant solid tumors for whom there is no available standard therapy likely to confer clinical benefit, evaluating the safety, tolerability, preliminary antitumor activity, pharmacokinetics (PK), pharmacodynamics (PD), and immunogenicity of GEN1053. The trial will be conducted as follows: * The Dose Escalation part (Part 1) will explore the safety of escalating doses of GEN1053 as monotherapy (phase 1) * The Expansion part (Part 2) is planned to provide additional safety and initial antitumor activity information of the Recommended Phase 2 dose (RP2D) for GEN1053 monotherapy in selected tumor indications, as well as more detailed data related to the mode of action (MoA).
Interventions
BIOLOGICALGEN1053
GEN1053 will be administered as an intravenous (IV) infusion every 3rd week. The dose levels will be determined by the starting dose and the escalation steps taken in the trial.
Sponsors
BioNTech SE
Genmab
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Sequential assignment
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: For both the Dose Escalation and Expansion parts: * Be ≥18 years of age. * Have measurable disease according to RECIST 1.1 * Provide all pre-baseline scans since failure of last prior therapy (ie radiographic PD), if available * Have Eastern Cooperative Oncology Group performance status ≤1. * Have organ and bone marrow function as follows: Bone marrow / hematological function: * Absolute neutrophil count (ANC) ≥1.5×10\^9/L * Hemoglobin ≥9.0 g/dL * Platelet count ≥150×10\^9/L Liver function: * Total bilirubin ≤ upper limit of normal (ULN) * Alanine aminotransferase ≤1.5×ULN * Aspartate aminotransferase ≤1.5×ULN * Albumin ≥30 g/L Coagulation status: * Prothrombin time (PT)/International normalized ratio ≤1.5 * Activated partial thromboplastin time (aPTT) ≤1.5×ULN * Renal function: Glomerular filtration rate ≥45 mL/min/1.73 m², according to the abbreviated Modification of Diet in Renal Disease equation For Monotherapy Dose Escalation (phase 1) only: * Subjects with histologically or cytologically confirmed non-CNS solid tumors that are metastatic or advanced. * Subjects who have progressed on standard of care therapy or for whom there is no available standard therapy likely to provide clinical benefit, or who are not candidates for or refuse such available therapy, and for whom, in the opinion of the investigator, experimental therapy with GEN1053 may be beneficial. * Fresh biopsies mandatory for all patients in Monotherapy Dose Escalation For the Expansion part Only: •Subjects with histologically or cytologically confirmed diagnosis of recurrent, unresectable or metastatic HNSCC, who have progressed on standard of care therapy or do not have any further available standard therapy or are not candidates for or refuse standard therapy (if subjects had access), and for whom experimental therapy with GEN1053 may be beneficial in the opinion of the investigator. Key
Exclusion criteria
(all parts): * Has uncontrolled intercurrent illness, including but not limited to: * Ongoing or active infection requiring IV treatment with anti-infective therapy administered less than 2 weeks prior to first dose. * Symptomatic congestive heart failure (Grade III or IV as classified by the New York Heart Association), unstable angina pectoris or cardiac arrhythmia. * Uncontrolled hypertension defined as systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥100 mm Hg, despite optimal medical management. * Prolonged QTc interval at baseline of ≥470 milliseconds using Fridericia's QT correction formula. * Ongoing or recent (within 1 year) evidence of significant autoimmune disease that required treatment with systemic immunosuppressive treatments, which may suggest risk for irAEs. * History of grade 3 or higher irAEs that led to treatment discontinuation of a CPI. * History of chronic liver disease or evidence of hepatic cirrhosis. * Evidence of interstitial lung disease. * Ongoing pneumonitis or history of non-infectious pneumonitis that has required steroids. * Known platelet function defects * Prior therapy: * Radiotherapy within 14 days prior to first GEN1053 administration. Palliative radiotherapy will be allowed. * Treatment with an anti-cancer agent (within 28 days or after at least 5 half-lives of the drug, whichever is shorter), prior to GEN1053 administration. * Subject with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first treatment. Inhaled or topical steroids, and adrenal or pituitary replacement steroid \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease. NOTE: Other protocol defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | Day 1 up to Day 21 | The occurrence of any of the following toxicities, assessed as related to trial treatment, were considered DLTs: All Grade 5 events, Grade 4 anaphylaxis, infusion-related reactions and neutropenia for ≥7 days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, Grade 4 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin elevation/Grade 3 that did not recover to ≤Grade 1 within 14 days, AST or ALT elevations ≥Grade 2 with concomitant bilirubin \>2.0×upper limit of normal with no signs of cholestasis, any Grade 4 immune-related adverse event (irAE), Grade 3 irAEs that did not improve to ≤Grade 1 within 7 days (with exceptions), Grade 4 cytokine release syndrome (CRS), Grade 3 CRS not resolved to ≤Grade 2 within 48 hrs following adequate intervention, any other ≥Grade 3 nonhematological adverse event (AE) during the first GEN1053 treatment cycle (with exceptions), cycle=3 weeks. |
| Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | Up to approximately 1.5 years | An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal safety laboratory parameter finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was defined as an AE occurring or worsening after first dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Elimination Half-life (t1/2) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Clearance (CL) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing the pharmacokinetics (PK) of GEN1053. |
| Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 through end of safety follow up (60 days after last dose [cycles were 3 weeks]), up to approximately 1.5 years | Venous blood samples were drawn for analysis of ADAs in serum samples. |
| Objective Response Rate (ORR) | Up to approximately 1.5 years | ORR was defined as the number of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) (ie, responders), as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 millimeters (mm) in all pathological target and non-target lymph nodes, and normalization of tumor marker level (if applicable). PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Data are presented for the number of participants with ORR. |
| Disease Control Rate (DCR) | Up to approximately 1.5 years | DCR was defined as the number of participants with CR, PR, or stable disease (SD). CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 mm in all pathological target and non-target lymph nodes, and normalization of tumor marker level (if applicable). PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters (nadir) while on study. Data are presented for the number of participants with DCR. |
| Duration of Response (DOR) | Up to approximately 1.5 years | DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death due to any cause in participants whose confirmed BOR was CR or PR. |
| AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
| Volume of Distribution (Vz) of GEN1053 | Cycle 1 and Cycle 3 (cycles were 3 weeks) | Venous blood samples were collected for analyzing concentrations of GEN1053. |
Countries
Spain, United States
Participant flow
Pre-assignment details
This study was early terminated and only the GEN1053 monotherapy dose escalation was initiated and completed. The study was terminated prior to the start of the Dose Expansion Phase.
Participants by arm
| Arm | Count |
|---|---|
| GEN1053 Dose Level 1 Q3W Participants with malignant solid tumors were treated with dose level 1 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 1 |
| GEN1053 Dose Level 2 Q3W Participants with malignant solid tumors were treated with dose level 2 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 1 |
| GEN1053 Dose Level 3 Q3W Participants with malignant solid tumors were treated with dose level 3 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 3 |
| GEN1053 Dose Level 4 Q3W Participants with malignant solid tumors were treated with dose level 4 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 1 |
| GEN1053 Dose Level 5 Q3W Participants with malignant solid tumors were treated with dose level 5 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 6 |
| GEN1053 Dose Level 6 Q3W Participants with malignant solid tumors were treated with dose level 6 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 3 |
| GEN1053 Dose Level 7 Q3W Participants with malignant solid tumors were treated with dose level 7 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 7 |
| GEN1053 Dose Level 8 Q3W Participants with malignant solid tumors were treated with dose level 8 of GEN1053 Q3W by IV infusion. Dose Level 1 was the lowest dose, and doses were increased incrementally up to Dose Level 8, which was the highest dose. | 9 |
| Total | 31 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 |
|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Death | 1 | 0 | 3 | 1 | 3 | 2 | 4 | 6 |
| Overall Study | Sponsor Decision | 0 | 1 | 0 | 0 | 2 | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 1 |
Baseline characteristics
| Characteristic | Total | GEN1053 Dose Level 2 Q3W | GEN1053 Dose Level 1 Q3W | GEN1053 Dose Level 3 Q3W | GEN1053 Dose Level 4 Q3W | GEN1053 Dose Level 5 Q3W | GEN1053 Dose Level 6 Q3W | GEN1053 Dose Level 7 Q3W | GEN1053 Dose Level 8 Q3W |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 12 Participants | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 2 Participants | 2 Participants | 4 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 19 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 3 Participants | 9 Participants |
| Age, Continuous | 62.1 years STANDARD_DEVIATION 11.4 | 78 years | 79 years | 62.3 years STANDARD_DEVIATION 13.9 | 57 years | 55.2 years STANDARD_DEVIATION 13.1 | 66 years STANDARD_DEVIATION 16.1 | 68.7 years STANDARD_DEVIATION 8.4 | 57 years STANDARD_DEVIATION 5.7 |
| 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 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Missing | 21 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 7 Participants | 5 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 Not Hispanic or Latino | 8 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 4 Participants |
| Race/Ethnicity, Customized Not Reported | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 31 Participants | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants | 3 Participants | 7 Participants | 9 Participants |
| Region of Enrollment Spain | 21 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 4 Participants | 2 Participants | 7 Participants | 5 Participants |
| Region of Enrollment United States of America (The) | 10 Participants | 1 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 4 Participants |
| Sex: Female, Male Female | 16 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 4 Participants | 2 Participants | 5 Participants | 4 Participants |
| Sex: Female, Male Male | 15 Participants | 0 Participants | 1 Participants | 3 Participants | 1 Participants | 2 Participants | 1 Participants | 2 Participants | 5 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 | 0 / 1 | 3 / 3 | 1 / 1 | 3 / 6 | 2 / 3 | 4 / 7 | 6 / 9 |
| other Total, other adverse events | 1 / 1 | 1 / 1 | 3 / 3 | 1 / 1 | 6 / 6 | 3 / 3 | 7 / 7 | 9 / 9 |
| serious Total, serious adverse events | 0 / 1 | 1 / 1 | 0 / 3 | 0 / 1 | 1 / 6 | 1 / 3 | 0 / 7 | 3 / 9 |
Outcome results
Primary
Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE)
An adverse event (AE) was any untoward medical occurrence in a participant or clinical trial participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE was therefore any unfavorable and unintended sign (including an abnormal safety laboratory parameter finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was defined as an AE occurring or worsening after first dose. A summary of all Serious Adverse Events and Other Adverse Events (nonserious) regardless of causality is located in the 'Reported Adverse Events' Section.
Time frame: Up to approximately 1.5 years
Population: Measured in the Safety Analysis Set, which included all participants who received at least 1 dose of trial drug. Participants were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1053 Dose Level 1 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 1 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 6 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 3 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 7 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With At Least One Treatment-emergent Adverse Event (TEAE) | 9 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs)
The occurrence of any of the following toxicities, assessed as related to trial treatment, were considered DLTs: All Grade 5 events, Grade 4 anaphylaxis, infusion-related reactions and neutropenia for ≥7 days, Grade 3/4 febrile neutropenia, Grade 4 thrombocytopenia, Grade 3 thrombocytopenia with clinically significant bleeding, Grade 4 anemia, Grade 4 aspartate aminotransferase (AST), alanine aminotransferase (ALT), or bilirubin elevation/Grade 3 that did not recover to ≤Grade 1 within 14 days, AST or ALT elevations ≥Grade 2 with concomitant bilirubin \>2.0×upper limit of normal with no signs of cholestasis, any Grade 4 immune-related adverse event (irAE), Grade 3 irAEs that did not improve to ≤Grade 1 within 7 days (with exceptions), Grade 4 cytokine release syndrome (CRS), Grade 3 CRS not resolved to ≤Grade 2 within 48 hrs following adequate intervention, any other ≥Grade 3 nonhematological adverse event (AE) during the first GEN1053 treatment cycle (with exceptions), cycle=3 weeks.
Time frame: Day 1 up to Day 21
Population: Measured in the Safety Analysis Set, which included all participants who received at least 1 dose of trial drug. Participants were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1053 Dose Level 1 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Dose Limiting Toxicities (DLTs) | 1 Participants |
Secondary
Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 0.5620 day*ug/mL | — |
| GEN1053 Dose Level 2 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 3 | 0.1930 day*ug/mL | — |
| GEN1053 Dose Level 2 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 1.5300 day*ug/mL | — |
| GEN1053 Dose Level 3 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 21.8315 day*ug/mL | Geometric Coefficient of Variation 30.886 |
| GEN1053 Dose Level 4 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 15.2000 day*ug/mL | — |
| GEN1053 Dose Level 5 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 86.0185 day*ug/mL | Geometric Coefficient of Variation 62.0662 |
| GEN1053 Dose Level 5 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 3 | 204.3491 day*ug/mL | Geometric Coefficient of Variation 19.5536 |
| GEN1053 Dose Level 6 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 3 | 423.0000 day*ug/mL | — |
| GEN1053 Dose Level 6 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 379.6819 day*ug/mL | Geometric Coefficient of Variation 41.9278 |
| GEN1053 Dose Level 7 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 678.2510 day*ug/mL | Geometric Coefficient of Variation 55.6633 |
| GEN1053 Dose Level 7 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 3 | 1510.1353 day*ug/mL | Geometric Coefficient of Variation 51.8536 |
| GEN1053 Dose Level 8 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 3 | 1985.3056 day*ug/mL | Geometric Coefficient of Variation 33.6209 |
| GEN1053 Dose Level 8 Q3W | Area Under the Concentration-time Curve (AUC) From Time Zero to Last Quantifiable Measurement (AUClast) of GEN1053 | Cycle 1 | 1190.8115 day*ug/mL | Geometric Coefficient of Variation 69.3078 |
Secondary
AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 0.8170 day*ug/mL | — |
| GEN1053 Dose Level 2 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 1.9200 day*ug/mL | — |
| GEN1053 Dose Level 3 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 21.8315 day*ug/mL | Geometric Coefficient of Variation 30.886 |
| GEN1053 Dose Level 5 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 3 | 203.9020 day*ug/mL | Geometric Coefficient of Variation 19.9691 |
| GEN1053 Dose Level 5 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 100.5407 day*ug/mL | Geometric Coefficient of Variation 19.7816 |
| GEN1053 Dose Level 6 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 402.5411 day*ug/mL | Geometric Coefficient of Variation 37.4881 |
| GEN1053 Dose Level 7 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 835.4647 day*ug/mL | Geometric Coefficient of Variation 28.4628 |
| GEN1053 Dose Level 7 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 3 | 1656.9616 day*ug/mL | Geometric Coefficient of Variation 36.6222 |
| GEN1053 Dose Level 8 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 3 | 1842.9867 day*ug/mL | Geometric Coefficient of Variation 26.7838 |
| GEN1053 Dose Level 8 Q3W | AUC From Time Zero Over the Dosing Interval (AUCtau) of GEN1053 | Cycle 1 | 1392.1084 day*ug/mL | Geometric Coefficient of Variation 37.2599 |
Secondary
Clearance (CL) of GEN1053
Venous blood samples were collected for analyzing the pharmacokinetics (PK) of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 2450.0 milliliters (mL)/day | — |
| GEN1053 Dose Level 2 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 3120.0 milliliters (mL)/day | — |
| GEN1053 Dose Level 3 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 916.7 milliliters (mL)/day | Geometric Coefficient of Variation 30.8 |
| GEN1053 Dose Level 5 Q3W | Clearance (CL) of GEN1053 | Cycle 3 | 293.1 milliliters (mL)/day | Geometric Coefficient of Variation 19.5 |
| GEN1053 Dose Level 5 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 594.0 milliliters (mL)/day | Geometric Coefficient of Variation 19.7 |
| GEN1053 Dose Level 6 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 491.3 milliliters (mL)/day | Geometric Coefficient of Variation 35.6 |
| GEN1053 Dose Level 7 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 471.7 milliliters (mL)/day | Geometric Coefficient of Variation 29.5 |
| GEN1053 Dose Level 7 Q3W | Clearance (CL) of GEN1053 | Cycle 3 | 244.5 milliliters (mL)/day | Geometric Coefficient of Variation 36 |
| GEN1053 Dose Level 8 Q3W | Clearance (CL) of GEN1053 | Cycle 3 | 435.2 milliliters (mL)/day | Geometric Coefficient of Variation 27.3 |
| GEN1053 Dose Level 8 Q3W | Clearance (CL) of GEN1053 | Cycle 1 | 567.7 milliliters (mL)/day | Geometric Coefficient of Variation 39.1 |
Secondary
Disease Control Rate (DCR)
DCR was defined as the number of participants with CR, PR, or stable disease (SD). CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 mm in all pathological target and non-target lymph nodes, and normalization of tumor marker level (if applicable). PR was defined as ≥30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD), taking as reference the smallest sum diameters (nadir) while on study. Data are presented for the number of participants with DCR.
Time frame: Up to approximately 1.5 years
Population: Measured in the Full Analysis Set, which included all participants who received at least 1 dose of trial drug. Participants were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1053 Dose Level 1 Q3W | Disease Control Rate (DCR) | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Disease Control Rate (DCR) | 1 Participants |
| GEN1053 Dose Level 3 Q3W | Disease Control Rate (DCR) | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Disease Control Rate (DCR) | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Disease Control Rate (DCR) | 2 Participants |
| GEN1053 Dose Level 6 Q3W | Disease Control Rate (DCR) | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Disease Control Rate (DCR) | 2 Participants |
| GEN1053 Dose Level 8 Q3W | Disease Control Rate (DCR) | 2 Participants |
Secondary
Duration of Response (DOR)
DOR was defined as the time from the first documentation of objective tumor response (CR or PR) to the date of first PD or death due to any cause in participants whose confirmed BOR was CR or PR.
Time frame: Up to approximately 1.5 years
Population: Measured in the Full Analysis Set (which included all participants who received at least 1 dose of trial drug) in those participants whose confirmed BOR was CR or PR. Participants were analyzed according to the actual trial treatment received. Overall number of participants analyzed = 0 as no participants had a confirmed BOR of CR or PR.
Secondary
Elimination Half-life (t1/2) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 1.2200 days | — |
| GEN1053 Dose Level 2 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 0.8750 days | — |
| GEN1053 Dose Level 3 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 4.5977 days | Geometric Coefficient of Variation 13.0224 |
| GEN1053 Dose Level 5 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 3 | 13.4236 days | Geometric Coefficient of Variation 53.5705 |
| GEN1053 Dose Level 5 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 7.1235 days | Geometric Coefficient of Variation 53.5614 |
| GEN1053 Dose Level 6 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 9.1195 days | Geometric Coefficient of Variation 30.0207 |
| GEN1053 Dose Level 7 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 10.0111 days | Geometric Coefficient of Variation 81.6893 |
| GEN1053 Dose Level 7 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 3 | 15.0597 days | Geometric Coefficient of Variation 27.0838 |
| GEN1053 Dose Level 8 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 3 | 17.2624 days | Geometric Coefficient of Variation 43.0077 |
| GEN1053 Dose Level 8 Q3W | Elimination Half-life (t1/2) of GEN1053 | Cycle 1 | 9.0787 days | Geometric Coefficient of Variation 100.0112 |
Secondary
Maximum (Peak) Concentration (Cmax) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 0.530 micrograms (μg)/mL | — |
| GEN1053 Dose Level 2 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 3 | 1.450 micrograms (μg)/mL | — |
| GEN1053 Dose Level 2 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 1.570 micrograms (μg)/mL | — |
| GEN1053 Dose Level 3 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 5.583 micrograms (μg)/mL | Geometric Coefficient of Variation 27.187 |
| GEN1053 Dose Level 4 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 12.000 micrograms (μg)/mL | — |
| GEN1053 Dose Level 5 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 16.862 micrograms (μg)/mL | Geometric Coefficient of Variation 8.824 |
| GEN1053 Dose Level 5 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 3 | 20.970 micrograms (μg)/mL | Geometric Coefficient of Variation 11.732 |
| GEN1053 Dose Level 6 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 3 | 60.400 micrograms (μg)/mL | — |
| GEN1053 Dose Level 6 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 60.854 micrograms (μg)/mL | Geometric Coefficient of Variation 44.313 |
| GEN1053 Dose Level 7 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 124.869 micrograms (μg)/mL | Geometric Coefficient of Variation 22.05 |
| GEN1053 Dose Level 7 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 3 | 159.509 micrograms (μg)/mL | Geometric Coefficient of Variation 26.51 |
| GEN1053 Dose Level 8 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 3 | 306.525 micrograms (μg)/mL | Geometric Coefficient of Variation 31.455 |
| GEN1053 Dose Level 8 Q3W | Maximum (Peak) Concentration (Cmax) of GEN1053 | Cycle 1 | 218.641 micrograms (μg)/mL | Geometric Coefficient of Variation 24.465 |
Secondary
Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053
Venous blood samples were drawn for analysis of ADAs in serum samples.
Time frame: Cycle 1 Day 1 through end of safety follow up (60 days after last dose [cycles were 3 weeks]), up to approximately 1.5 years
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 1 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 10 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 2 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 20 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 8 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 12 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | End of Treatment | 1 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 4 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 6 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 3 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 18 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 16 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Safety Follow Up 2 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 1 Day 1 | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Number of Participants With Anti-drug Antibodies (ADAs) to GEN1053 | Cycle 14 Day 1 | 0 Participants |
Secondary
Objective Response Rate (ORR)
ORR was defined as the number of participants with best overall response (BOR) of confirmed complete response (CR) or confirmed partial response (PR) (ie, responders), as per local review and according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR was defined as all of the following: disappearance of all target and non-target tumor lesions, and reduction in short axis to \<10 millimeters (mm) in all pathological target and non-target lymph nodes, and normalization of tumor marker level (if applicable). PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Data are presented for the number of participants with ORR.
Time frame: Up to approximately 1.5 years
Population: Measured in the Full Analysis Set, which included all participants who received at least 1 dose of trial drug. Participants were analyzed according to the actual trial treatment received.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GEN1053 Dose Level 1 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 2 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 3 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 4 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 5 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 6 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 7 Q3W | Objective Response Rate (ORR) | 0 Participants |
| GEN1053 Dose Level 8 Q3W | Objective Response Rate (ORR) | 0 Participants |
Secondary
Predose Trough Concentration (Ctrough) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 0.0250 ug/mL | — |
| GEN1053 Dose Level 2 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 0.0250 ug/mL | — |
| GEN1053 Dose Level 3 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 0.1322 ug/mL | Geometric Coefficient of Variation 58.7685 |
| GEN1053 Dose Level 5 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 3 | 4.3705 ug/mL | Geometric Coefficient of Variation 53.5677 |
| GEN1053 Dose Level 5 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 1.5722 ug/mL | Geometric Coefficient of Variation 60.7405 |
| GEN1053 Dose Level 6 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 6.0890 ug/mL | Geometric Coefficient of Variation 132.292 |
| GEN1053 Dose Level 7 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 24.8853 ug/mL | Geometric Coefficient of Variation 4.2283 |
| GEN1053 Dose Level 7 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 3 | 58.5326 ug/mL | Geometric Coefficient of Variation 12.2317 |
| GEN1053 Dose Level 8 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 3 | 56.3000 ug/mL | — |
| GEN1053 Dose Level 8 Q3W | Predose Trough Concentration (Ctrough) of GEN1053 | Cycle 1 | 33.6922 ug/mL | Geometric Coefficient of Variation 28.1602 |
Secondary
Time to Maximum (Peak) Concentration (Tmax) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0620 days | — |
| GEN1053 Dose Level 2 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 3 | 0.1350 days | — |
| GEN1053 Dose Level 2 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0600 days | — |
| GEN1053 Dose Level 3 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0583 days | Geometric Coefficient of Variation 3.5988 |
| GEN1053 Dose Level 4 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.1390 days | — |
| GEN1053 Dose Level 5 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 3 | 0.1023 days | Geometric Coefficient of Variation 64.0898 |
| GEN1053 Dose Level 5 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0855 days | Geometric Coefficient of Variation 65.523 |
| GEN1053 Dose Level 6 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 3 | 0.1390 days | — |
| GEN1053 Dose Level 6 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0760 days | Geometric Coefficient of Variation 45.9942 |
| GEN1053 Dose Level 7 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0826 days | Geometric Coefficient of Variation 75.6636 |
| GEN1053 Dose Level 7 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 3 | 0.0784 days | Geometric Coefficient of Variation 43.4302 |
| GEN1053 Dose Level 8 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 3 | 0.0746 days | Geometric Coefficient of Variation 49.4225 |
| GEN1053 Dose Level 8 Q3W | Time to Maximum (Peak) Concentration (Tmax) of GEN1053 | Cycle 1 | 0.0953 days | Geometric Coefficient of Variation 60.7249 |
Secondary
Volume of Distribution (Vz) of GEN1053
Venous blood samples were collected for analyzing concentrations of GEN1053.
Time frame: Cycle 1 and Cycle 3 (cycles were 3 weeks)
Population: Measured in the Pharmacokinetic (PK) Analysis Set, which included all participants who received at least 1 dose of trial drug and who provided at least 1 evaluable PK sample. Overall number of participants analyzed = participants with evaluable data for the outcome measure. Number analyzed = participants with evaluable data at the specified timepoint.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| GEN1053 Dose Level 1 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 4300.0 mL | — |
| GEN1053 Dose Level 2 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 3950.0 mL | — |
| GEN1053 Dose Level 3 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 6077.1 mL | Geometric Coefficient of Variation 17.9 |
| GEN1053 Dose Level 5 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 3 | 5683.6 mL | Geometric Coefficient of Variation 36.1 |
| GEN1053 Dose Level 5 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 6108.9 mL | Geometric Coefficient of Variation 34.2 |
| GEN1053 Dose Level 6 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 6455.8 mL | Geometric Coefficient of Variation 8.1 |
| GEN1053 Dose Level 7 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 6808.7 mL | Geometric Coefficient of Variation 73.4 |
| GEN1053 Dose Level 7 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 3 | 5302.1 mL | Geometric Coefficient of Variation 9.1 |
| GEN1053 Dose Level 8 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 3 | 10834.8 mL | Geometric Coefficient of Variation 77.5 |
| GEN1053 Dose Level 8 Q3W | Volume of Distribution (Vz) of GEN1053 | Cycle 1 | 7434.6 mL | Geometric Coefficient of Variation 70.8 |