Non-CNS Tumor
Conditions
Brief summary
The main purpose is to assess the safety and clinical activity of GEN1042 in combination with radiotherapy or GEN1042 in combination with radiotherapy and pembrolizumab as a treatment option for participants with metastatic solid tumors.
Detailed description
The study will be conducted in two parts: Part 1 (dose-finding) and Part 2 (randomization). Part 1 will evaluate the safety of immunoradiotherapy combinations and establish the dose(s) to be evaluated in Part 2. Part 2 will evaluate the anti-tumor activity of immunoradiotherapy combinations at the established dose(s) from Part 1. Participants in both parts are treated with one of the following combinations: * Radiotherapy + GEN1042 * Radiotherapy + GEN1042 + Pembrolizumab While participants in Part 1 are assigned sequentially (GEN1042 without pembrolizumab is investigated first), participants in Part 2 are randomized 1:1 in the two treatment arms.
Interventions
Sponsors
Genmab
BioNTech SE
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 is sequential, Part 2 is parallel (randomized)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: * Participants with histologically confirmed non-central nervous system (CNS) solid tumor that is metastatic and for whom there is no available standard therapy. * At least 18 years of age. * Signed informed consent prior to any screening procedures. * Measurable disease according to RECIST v1.1. * Life expectancy of \>3 months. * Qualify for palliative radiotherapy as an available option for disease management. * Eastern Cooperative Oncology Group (ECOG) 0-1. * Normal or adequate liver, renal, cardiac and bone marrow function. Key
Exclusion criteria
* Prior malignancy except for non-melanoma skin cancers and in situ cancers. * Condition contraindicating radiotherapy. * Rapidly progressing disease. * Active, known or suspected autoimmune disease. * History of non-infectious pneumonitis that required steroids or currently has pneumonitis. * Contraindications to the use of pembrolizumab. * Condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications within 14 days of first treatment. * Received an allogeneic tissue/solid organ transplant. * Active infection requiring systemic therapy. Note: Other protocol defined inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) | 21 days | A DLT was defined as any grade 5 toxicity, treatment-related toxicity that caused the participant to discontinue treatment during Cycle 1, febrile neutropenia grade 3 or grade 4, grade 3 thrombocytopenia associated with clinically significant bleeding, grade 4 thrombocytopenia of any duration, grade 4 anemia, any grade ≥3 non-hematologic clinical (non-laboratory) toxicity with exceptions per protocol, any grade 3 or grade 4 non-hematologic laboratory value if clinically significant medical intervention was required to treat the participant or the abnormality led to hospitalization, or the abnormality persisted for \>7 days, and the abnormality resulted in a drug-induced liver injury (DILI) as defined by Hy's Law. Toxicities were graded for severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE v5.0). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Anti-drug Antibodies (ADAs) | Up to approximately 2 years 5 months | Venous blood samples were drawn for analysis of ADAs. Data are reported for the number of participants with an on-treatment ADA status of positive. For on-treatment results, a participant was considered ADA positive if either 1) ADA was negative at baseline and at least one on-treatment result was positive 2) positive at baseline and at least one positive on-treatment result with at least one titer higher than baseline. |
| Objective Response Rate (ORR) | Up to approximately 2 years 5 months | ORR was defined as the percentage of participants with a confirmed best overall response (BOR) of complete response (CR) or partial response (PR) based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST) v1.1 as assessed by investigator. 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 lesions. PR was defined as ≥30 percent (%) decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. |
| Duration of Response (DOR) | Up to approximately 2 years 5 months | DOR was defined as the time from the onset date of response to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator. |
| Disease Control Rate (DCR) | Up to approximately 2 years 5 months | DCR was defined as the percentage of participants with BOR of CR, PR, and stable disease (SD) according to RECIST v1.1 as assessed by investigator. 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 lesions. PR was defined as ≥30 percent (%) 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). |
| Progression Free Survival (PFS) | Up to approximately 2 years 5 months | PFS was defined as the time from the date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to the date of the first documented progression or death due to any cause based on RECIST v1.1 as assessed by investigator. |
| Overall Survival (OS) | Up to approximately 2 years 5 months | OS was defined as the time from date of randomization (or date of first administration of GEN1042 ± pembrolizumab treatment for participants in Part 1) to date of death due to any cause. |
| Number of Participants With Abscopal Response in Non-irradiated Target Lesions As Assessed by the Investigator | Up to approximately 2 years 5 months | An abscopal response described radiotherapy (RT)-induced immune-mediated tumor regression at sites distant to the irradiated field. For the purpose of this trial, an abscopal response was defined as a reduction of at least 30% in diameter of the best responding unirradiated target lesion. Data are reported for the number of participants with abscopal response in non-irradiated target lesions as assessed by the investigator. |
| Blood Concentration of GEN1042 Over Time | At multiple timepoints (as described in the "Outcome Measure Description" field between Cycle 1 Day 1 up to Safety Follow Up [up to approximately Day 517]). Cycles were 21 days in length. | Blood samples were collected for measurement of serum concentrations of GEN1042. Data are reported for Cycle (C)1 Day (D)1 pre-dose and end of infusion (EOI), C1D8, C1D15, C2D1 pre-dose and end of infusion, C2D8, C2D15, C3D1 pre-dose and end of infusion,C4D1 pre-dose and end of infusion,C4D8, C5D1 pre-dose and end of infusion, C7D1 pre-dose and end of infusion,C11D1 end of infusion,C12D1 end of infusion+2 hours,C15D1 end of infusion,C19D1 end of infusion,C23D1 end of infusion, End of Treatment (\~D487) and Safety Follow Up (\~D517). Cycles were 21 days in length. |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 2 years 5 months | 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 laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. A TEAE was any AE that occurred or worsened after the first dose of trial treatment. A summary of all Serious Adverse Events and Other Adverse Events (non-serious) regardless of causality is located in the 'Reported Adverse Events' Section. |
Countries
France
Contacts
STUDY_DIRECTORStudy Official
Genmab
Participant flow
Pre-assignment details
This trial was planned to be conducted in two parts, Part 1 and Part 2. The trial was terminated early after Part 1 (27 Gy Cohorts). Part 2 was not initiated.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 5 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age, Continuous | 52.3 years STANDARD_DEVIATION 10.1 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 0 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 0 Participants |
| Race/Ethnicity, Customized Not Reported | 6 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized Unknown | 6 Participants |
| Race/Ethnicity, Customized White | 0 Participants |
| Region of Enrollment France | 6 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 4 / 6 | 3 / 7 |
| other Total, other adverse events | 6 / 6 | 7 / 7 |
| serious Total, serious adverse events | 2 / 6 | 2 / 7 |
Outcome results
None listed