SCC - Squamous Cell Carcinoma of Skin
Conditions
Keywords
cSCC, metastatic, locally advanced
Brief summary
This is an open-label, non comparative, non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms
Detailed description
This is an open-label, non-randomized, Phase II study. Patients will be enrolled in 2 treatment arms (Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + pembrolizumab combination therapy), both consisting of 2 stages whereas Arm B starts with a safety run in portion. Enrollment follows an optimal Simon's 2-stage design with an interim analysis of treatment response after Stage 1 prior to patient enrollment into Stage 2. Arm B will start after ≥3 patients have been treated in Arm A and no toxicity concerns have emerged. In a safety run-in part of Arm B, escalating doses of Vilobelimab will be investigated in combination with pembrolizumab in order to identify the maximum tolerated dose (MTD) or recommended Phase II dose (RP2D). Patients will be treated until progression, occurrence of unacceptable toxicity, or treatment discontinuation for any other reason.
Interventions
DRUGVilobelimab
Vilobelimab Monotherapy
DRUGVilobelimab + pembrolizumab combination therapy
Vilobelimab + pembrolizumab combination therapy
Sponsors
Merck Sharp & Dohme LLC
InflaRx GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Arm A: Vilobelimab monotherapy; Arm B: Vilobelimab + in combination with approved dosing scheme of pembrolizumab
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* At least 18 years of age on day of signing informed consent * Patients with biopsy-proven, histologically or cytologically confirmed (a.) locally advanced cSCC not amenable for curative treatment or (b.) metastatic cSCC. Patients must have been treated with all approved therapies for (a.) inoperable locally advanced cSCC contraindicated for radiation therapy or (b.) metastatic cSCC. All patients to be included must have progressed on PD-1- or PD-L1-inhibitory antibody therapy. * Patients must have progressed on treatment with an anti-PD-1/L1 monoclonal antibody (mAb) administered either as monotherapy or in combination with other checkpoint inhibitors or other therapies. PD-1 treatment progression is defined by meeting all of the following criteria: 1. Has received ≥2 doses of an anti-PD-1/L1 mAb that has been approved for treatment of cSCC or any solid tumor 2. Has demonstrated PD/iCPD after PD-1/L1 inhibitor treatment as defined by RECIST v1.1/iRECIST. The initial evidence of disease progression is to be confirmed by a second assessment ≥4 weeks from the date of the first documented disease progression, unless there is rapid clinical progression. 3. Disease progression has been documented within 12 weeks from the last dose of anti-PD-1/L1 mAb. * The PD-1-/PD-L1 infusion must have been the most recent treatment for locally advanced or metastatic cSCC. * In addition to providing the material for ensuring the diagnosis as stated in inclusion criterion 2a for patients with locally advanced cSCC, patients must consent to undergo the following biopsies (at each time point a punch biopsy of externally visible cSCC lesions or a biopsy of material from accessible metastases) for biomarker assessments: 1. At baseline prior to the first administration of the investigational therapy and if possible, within 7 days prior to initiation of study treatment administration (mandatory for all patients) 2. For Stage 2 patients only: on Cycle 2 Day 1 (±3 days) (mandatory) 3. For Stage 2 patients only: at the time of CR/iCR/PR/iPR (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative) 4. For Stage 2 patients only: At the time of tumor progression (optional, to be conducted only if the investigator considers this biopsy as clinically possible and potentially informative). * Patients must have the following minimum washout before first study treatment administration from previous treatments: 1. ≥4 weeks for mAbs, systemic cytotoxic anticancer therapy, treatment with other anticancer investigational agents 2. ≥3 weeks for local radiation therapy * Eastern Cooperative Oncology Group performance status (ECOG PS) status of ≤1 * Adequate organ function * Patient (or legally acceptable representative if applicable) provides written informed consent for the study.
Exclusion criteria
* Patients with limited cSCC, who do not require systemic therapy * Has known active central nervous system metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for ≥4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for ≥14 days prior to first dose of study treatment. * Has a diagnosis of immunodeficiency or autoimmune disease, or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 3 weeks prior the first dose of study treatment * Patients who have a history of (non-infectious) pneumonitis that required steroids or have current pneumonitis * Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or co-inhibitory T cell receptor (e.g., cytotoxic T-lymphocyte-associated antigen 4, OX 40, CD137) and was discontinued from that treatment due to a ≥Grade 3 irAE * Has severe hypersensitivity (≥Grade 3) to pembrolizumab or IFX-1 and/or any of their excipients or had a severe (≥Grade 3) infusion-related reaction to treatments with other mAbs * Patients who fulfil inclusion criterion 6 (washout times) but who have not recovered from side effects of such therapies * Has received a live vaccine within 30 days prior to the first dose of study treatment * Patients who have undergone major surgery \<4 weeks prior to starting study treatment * Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment * Patients with known ≥Grade 3 (per National Cancer Institute common terminology criteria for adverse events \[NCI CTCAE\] v5.0 criteria) active systemic or cutaneous viral, bacterial, or fungal infection * Patients with known history of Hepatitis B or C infections or known to be positive for Hepatitis B antigen (HBsAg)/ Hepatitis B virus (HBV) DNA or Hepatitis C Antibody or RNA. Active Hepatitis C is defined by a known positive Hep C Ab result and known quantitative HCV RNA results greater than the lower limits of detection of the assay. * Patients who have a history of human immunodeficiency virus infection * Patients who have a history of interstitial lung disease * Patients who have had an allogeneic tissue/solid organ transplant * Patients with a history of other malignancies during the past 5 years. * Patients who are pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 3 months after the last dose of IFX-1 or 120 days after the last dose of pembrolizumab * Women of childbearing potential (WOCBP) who have a positive serum pregnancy test result within 7 days before treatment * Male patients and WOCBP who do not agree to practice an effective method of contraception during study and until 3 months after last dose of IFX-1 or 120 days after last dose of pembrolizumab * Patients with congestive heart failure, Class III or IV, by New York Heart Association criteria * Patients with any serious underlying medical condition that would impair their ability to receive or tolerate the planned treatment * Patients with dementia or altered mental status that would preclude understanding and rendering of informed consent document
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Best Overall Response Rate (Best ORR) - Arm A and Arm B | Up to 36 months | Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and immunologic RECIST (iRECIST) for target lesions and assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions; Best Overall Response (OR) = CR + PR, from the start of the treatment until PD/recurrence. |
| Dose-limiting Toxicity (DLT) - Arm B | Cycle 1 Day 1 - Cycle 1 Day 36 | Frequency of dose-limiting toxicities (DLTs) by dose cohort. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS)- Arm A and Arm B | Up to 36 months | Overall survival is defined as the time from first study treatment administration to death. Patients alive when they discontinue the study are censored at their last recorded date of being alive. |
| Antidrug Antibodies (ADAs) - Arm A and Arm B | Up to 27 months | Development of human antidrug antibodies (ADAs) against Vilobelimab. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months. |
| Disease Control Rate - Arm A and Arm B | Up to 36 months | Disease control rate is defined as the relative number of patients achieving stable disease (SD/iSD), CR/iCR or PR/iPR according to modified RECIST v1.1 (including clinical response)/iRECIST response. |
| Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B | Up to 36 months | Duration of stable disease is defined as the time from first diagnosis of response or stable disease (i.e., CR/iCR/PR/iPR/SD/iSD) to progression (i.e. progressive disease (PD), unconfirmed progressive disease according to iRECIST (iUPD), confirmed progressive disease (iCPD)) or death. Responding and stable patients without progression are censored at their last visit/study treatment administration. Patients who never respond or have a stable disease are excluded from this analysis. |
| Plasma Concentration of Vilobelimab - Arm A and Arm B | Up to 27 months | The plasma concentration of vilobelimab was assessed at different time points pre- and post-dose. The post-dose Cycle 1 Day 22 values correspond to Cmax and the pre-dose Cycle 1 Day 8, pre-dose Cycle 1 Day 22, pre-dose Cycle 2 Day 1 and per-dose Cycle 5 Day 1 values to Ctrough. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months. |
| Quality of Life (QoL) - Arm A and Arm B | Up to 36 months | The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 version 3.0 measures the different aspects that define the quality of life of cancer patients or survivors. The reported total score ranges from 0 to 100 whereas a higher score represents a higher response level. The total score was calculated as mean of all 15 single scores. It was only calculated if all 15 single scores were non-missing (for more information see Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published by: European Organisation for Research and Treatment of Cancer, Brussels 2001.). The absolute changes from baseline are presented. |
| Progression-free Survival (PFS)- Arm A and Arm B | Up to 36 months | PFS is defined as the time from first study treatment administration to progression (i.e. PD, iUPD, iCPD) or death. Patients without progression are censored at their last visit/study treatment administration. |
Countries
Belgium, France, Germany, Spain, United States
Participant flow
Pre-assignment details
According to protocol stipulations, a participant is enrolled into the study if informed consent form is completed (signed and dated). This reflects the Protocol Enrollment: 30 participant number. Five (5) participants failed screening (after ICF signed) and were not assigned to and treated in the different Arms/Groups, constituting the Total Started in Participant Flow: 25 participant number.
Participants by arm
| Arm | Count |
|---|---|
| Arm A: Vilobelimab monotherapy; Vilobelimab monotherapy was administered as a 30-minute (-5 / +10 minutes) intravenous infusion as follows: 800 mg on Days 1, 4, 8, and 15, followed by 1600 mg Q2W starting on Day 22 of Cycle 1 until EOT | 10 |
| Arm B: Regimen 1: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 400 mg on Days 1, 4, 8, and 15, followed by 800 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle | 3 |
| Arm B: Regimen 2: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 600 mg on Days 1, 4, 8, and 15, followed by 1200 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle | 6 |
| Arm B: Regimen 3: Vilobelimab + pembrolizumab combination therapy; Vilobelimab was administered as a 30-minute (-5/+10 minutes) intravenous infusion as follows: 800 mg on Days 1, 4, 8, and 15, followed by 1600 mg Q2W starting on Day 22 of Cycle 1 until EOT. Vilobelimab treatment was combined with pembrolizumab, administered as a 30-minute (-5/+10 minutes) intravenous infusion at a dose of 400 mg starting at Day 8 of Cycle 1 and then Q6W on Day 1 of each treatment cycle | 6 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 7 | 2 | 4 | 1 |
| Overall Study | Due to premature study termination by sponsor | 2 | 0 | 1 | 3 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Arm B: Regimen 1: | Arm B: Regimen 2: | Arm A: | Arm B: Regimen 3: | Total |
|---|---|---|---|---|---|
| Age, Continuous | 81.3 years STANDARD_DEVIATION 13.3 | 72.8 years STANDARD_DEVIATION 10.6 | 74.0 years STANDARD_DEVIATION 13.4 | 70.8 years STANDARD_DEVIATION 9.6 | 73.8 years STANDARD_DEVIATION 11.6 |
| BMI at screening | 26.13 kg/m² STANDARD_DEVIATION 6.79 | 27.90 kg/m² STANDARD_DEVIATION 7.22 | 29.08 kg/m² STANDARD_DEVIATION 14.18 | 25.10 kg/m² STANDARD_DEVIATION 3.48 | 27.49 kg/m² STANDARD_DEVIATION 9.76 |
| Duration of cSCC | 5.0 years STANDARD_DEVIATION 1 | 3.3 years STANDARD_DEVIATION 2.1 | 4.4 years STANDARD_DEVIATION 7.4 | 4.0 years STANDARD_DEVIATION 3.5 | 4.1 years STANDARD_DEVIATION 4.9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants | 5 Participants | 10 Participants | 6 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Height at screening | 167.0 centimeter STANDARD_DEVIATION 2.6 | 160.3 centimeter STANDARD_DEVIATION 5.9 | 167.7 centimeter STANDARD_DEVIATION 12.1 | 169.0 centimeter STANDARD_DEVIATION 9.8 | 166.2 centimeter STANDARD_DEVIATION 9.7 |
| Histologic grade (TNM staging at initial diagnosis) G1 | 0 Participants | 0 Participants | 3 Participants | 2 Participants | 5 Participants |
| Histologic grade (TNM staging at initial diagnosis) G2 | 2 Participants | 2 Participants | 2 Participants | 2 Participants | 8 Participants |
| Histologic grade (TNM staging at initial diagnosis) G3 | 0 Participants | 3 Participants | 2 Participants | 0 Participants | 5 Participants |
| Histologic grade (TNM staging at initial diagnosis) G4 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Histologic grade (TNM staging at initial diagnosis) GX | 1 Participants | 1 Participants | 1 Participants | 1 Participants | 4 Participants |
| Histologic grade (TNM staging at initial diagnosis) Missing | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| H&P Borders Missing | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| H&P Borders Poorly defined | 1 Participants | 1 Participants | 4 Participants | 1 Participants | 7 Participants |
| H&P Borders Well defined | 2 Participants | 3 Participants | 4 Participants | 2 Participants | 11 Participants |
| H&P Immunosuppression - | 3 Participants | 6 Participants | 10 Participants | 4 Participants | 23 Participants |
| H&P Immunosuppression + | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| H&P Immunosuppression Missing | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| H&P Location/size - area H Missing | 0 Participants | 3 Participants | 2 Participants | 4 Participants | 9 Participants |
| H&P Location/size - area H No | 0 Participants | 2 Participants | 4 Participants | 0 Participants | 6 Participants |
| H&P Location/size - area H Yes | 3 Participants | 1 Participants | 4 Participants | 2 Participants | 10 Participants |
| H&P Location/size - area L <20 mm | 1 Participants | 2 Participants | 1 Participants | 1 Participants | 5 Participants |
| H&P Location/size - area L >=20 mm | 1 Participants | 2 Participants | 3 Participants | 1 Participants | 7 Participants |
| H&P Location/size - area L Missing | 1 Participants | 2 Participants | 6 Participants | 4 Participants | 13 Participants |
| H&P Location/size - area M <10 mm | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| H&P Location/size - area M >=10 mm | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 12 Participants |
| H&P Location/size - area M Missing | 1 Participants | 3 Participants | 4 Participants | 3 Participants | 11 Participants |
| H&P Neurologic symptoms - | 3 Participants | 6 Participants | 9 Participants | 5 Participants | 23 Participants |
| H&P Neurologic symptoms + | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| H&P Neurologic symptoms Missing | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| H&P Primary vs recurrent Missing | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| H&P Primary vs recurrent Primary | 0 Participants | 3 Participants | 3 Participants | 3 Participants | 9 Participants |
| H&P Primary vs recurrent Recurrent | 3 Participants | 3 Participants | 7 Participants | 1 Participants | 14 Participants |
| H&P Rapidly growing tumour - | 1 Participants | 4 Participants | 4 Participants | 3 Participants | 12 Participants |
| H&P Rapidly growing tumour + | 2 Participants | 2 Participants | 6 Participants | 1 Participants | 11 Participants |
| H&P Rapidly growing tumour Missing | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| H&P Site of prior RT or chronic inflammatory process - | 2 Participants | 4 Participants | 6 Participants | 3 Participants | 15 Participants |
| H&P Site of prior RT or chronic inflammatory process + | 1 Participants | 2 Participants | 4 Participants | 1 Participants | 8 Participants |
| H&P Site of prior RT or chronic inflammatory process Missing | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Metastases (TNM staging at initial diagnosis) M0 | 3 Participants | 5 Participants | 10 Participants | 5 Participants | 23 Participants |
| Metastases (TNM staging at initial diagnosis) M1 | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 2 Participants |
| Nodes (TNM staging at initial diagnosis) N0 | 2 Participants | 2 Participants | 6 Participants | 4 Participants | 14 Participants |
| Nodes (TNM staging at initial diagnosis) N1 | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 2 Participants |
| Nodes (TNM staging at initial diagnosis) N2 | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 2 Participants |
| Nodes (TNM staging at initial diagnosis) N3 | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Nodes (TNM staging at initial diagnosis) NX | 1 Participants | 1 Participants | 2 Participants | 0 Participants | 4 Participants |
| Pathology Acantholytic, adenosquamous, desmoplastic, or metaplastic subtypes - | 2 Participants | 5 Participants | 9 Participants | 3 Participants | 19 Participants |
| Pathology Acantholytic, adenosquamous, desmoplastic, or metaplastic subtypes + | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Pathology Acantholytic, adenosquamous, desmoplastic, or metaplastic subtypes Missing | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 4 Participants |
| Pathology Degree of differentiation Missing | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Pathology Degree of differentiation Poorly differentiated | 1 Participants | 4 Participants | 3 Participants | 0 Participants | 8 Participants |
| Pathology Degree of differentiation Well or moderately differentiated | 2 Participants | 2 Participants | 7 Participants | 5 Participants | 16 Participants |
| Pathology Depth: thickness or level of invasion <=6 mm and no invasion beyond subcutaneous fat | 2 Participants | 2 Participants | 3 Participants | 2 Participants | 9 Participants |
| Pathology Depth: thickness or level of invasion >6 mm or invasion beyond subcutaneous fat | 1 Participants | 2 Participants | 6 Participants | 2 Participants | 11 Participants |
| Pathology Depth: thickness or level of invasion Missing | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Pathology Perineural, lymphatic or vascular involvement - | 1 Participants | 3 Participants | 5 Participants | 3 Participants | 12 Participants |
| Pathology Perineural, lymphatic or vascular involvement + | 2 Participants | 1 Participants | 4 Participants | 1 Participants | 8 Participants |
| Pathology Perineural, lymphatic or vascular involvement Missing | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Primary diagnosis Locally advanced cSCC | 1 Participants | 1 Participants | 6 Participants | 2 Participants | 10 Participants |
| Primary diagnosis Metastatic cSCC | 2 Participants | 5 Participants | 4 Participants | 4 Participants | 15 Participants |
| Prognostic stage group TNM staging at initial diagnosis Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Prognostic stage group TNM staging at initial diagnosis Stage 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic stage group TNM staging at initial diagnosis Stage I | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 6 Participants |
| Prognostic stage group TNM staging at initial diagnosis Stage II | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Prognostic stage group TNM staging at initial diagnosis Stage III | 1 Participants | 1 Participants | 3 Participants | 1 Participants | 6 Participants |
| Prognostic stage group TNM staging at initial diagnosis Stage IV | 0 Participants | 3 Participants | 3 Participants | 2 Participants | 8 Participants |
| Prognostic stage group TNM staging at study entry Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic stage group TNM staging at study entry Stage 0 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic stage group TNM staging at study entry Stage I | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic stage group TNM staging at study entry Stage II | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic stage group TNM staging at study entry Stage III | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants |
| Prognostic stage group TNM staging at study entry Stage IV | 3 Participants | 6 Participants | 8 Participants | 5 Participants | 22 Participants |
| Prognostic staging system TNM staging at initial diagnosis AJCC 7 | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Prognostic staging system TNM staging at initial diagnosis AJCC 8 | 3 Participants | 6 Participants | 5 Participants | 5 Participants | 19 Participants |
| Prognostic staging system TNM staging at initial diagnosis BHW | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic staging system TNM staging at initial diagnosis Missing | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Prognostic staging system TNM staging at initial diagnosis Other | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Prognostic staging system TNM staging at study entry AJCC 7 | 0 Participants | 0 Participants | 3 Participants | 0 Participants | 3 Participants |
| Prognostic staging system TNM staging at study entry AJCC 8 | 3 Participants | 6 Participants | 6 Participants | 5 Participants | 20 Participants |
| Prognostic staging system TNM staging at study entry BHW | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic staging system TNM staging at study entry Missing | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prognostic staging system TNM staging at study entry Other | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 3 Participants | 6 Participants | 9 Participants | 6 Participants | 24 Participants |
| Region of Enrollment Belgium | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Region of Enrollment France | 1 Participants | 0 Participants | 3 Participants | 0 Participants | 4 Participants |
| Region of Enrollment Germany | 0 Participants | 3 Participants | 5 Participants | 2 Participants | 10 Participants |
| Region of Enrollment Spain | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 5 Participants |
| Region of Enrollment United States | 0 Participants | 0 Participants | 1 Participants | 2 Participants | 3 Participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 5 Participants | 5 Participants | 16 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 5 Participants | 1 Participants | 9 Participants |
| Tumor category (TNM staging at initial diagnosis) T1 | 2 Participants | 3 Participants | 1 Participants | 2 Participants | 8 Participants |
| Tumor category (TNM staging at initial diagnosis) T2 | 0 Participants | 1 Participants | 2 Participants | 0 Participants | 3 Participants |
| Tumor category (TNM staging at initial diagnosis) T3 | 1 Participants | 0 Participants | 4 Participants | 1 Participants | 6 Participants |
| Tumor category (TNM staging at initial diagnosis) T4 | 0 Participants | 2 Participants | 2 Participants | 2 Participants | 6 Participants |
| Tumor category (TNM staging at initial diagnosis) Tis | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Tumor category (TNM staging at initial diagnosis) TX | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants |
| Weight at screening | 73.33 kilogram STANDARD_DEVIATION 21.57 | 71.12 kilogram STANDARD_DEVIATION 16.44 | 82.56 kilogram STANDARD_DEVIATION 45.4 | 71.48 kilogram STANDARD_DEVIATION 9.59 | 76.05 kilogram STANDARD_DEVIATION 30.29 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 7 / 10 | 2 / 3 | 4 / 6 | 1 / 6 |
| other Total, other adverse events | 9 / 10 | 3 / 3 | 5 / 6 | 6 / 6 |
| serious Total, serious adverse events | 7 / 10 | 2 / 3 | 2 / 6 | 1 / 6 |
Outcome results
Primary
Best Overall Response Rate (Best ORR) - Arm A and Arm B
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) and immunologic RECIST (iRECIST) for target lesions and assessed by computed tomography (CT) or magnetic resonance imaging (MRI). Complete Response (CR): Disappearance of all target lesions; Partial Response (PR): ≥30% decrease in the sum of the diameters of target lesions; Best Overall Response (OR) = CR + PR, from the start of the treatment until PD/recurrence.
Time frame: Up to 36 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | ORR (Responder) | 1 Participants |
| Arm A: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | No post baseline measurement | 0 Participants |
| Arm A: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | Non-responder | 9 Participants |
| Arm B: Regimen 1: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | ORR (Responder) | 0 Participants |
| Arm B: Regimen 1: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | No post baseline measurement | 0 Participants |
| Arm B: Regimen 1: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | Non-responder | 3 Participants |
| Arm B: Regimen 2: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | Non-responder | 4 Participants |
| Arm B: Regimen 2: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | ORR (Responder) | 1 Participants |
| Arm B: Regimen 2: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | No post baseline measurement | 1 Participants |
| Arm B: Regimen 3: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | ORR (Responder) | 2 Participants |
| Arm B: Regimen 3: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | No post baseline measurement | 0 Participants |
| Arm B: Regimen 3: | Best Overall Response Rate (Best ORR) - Arm A and Arm B | Non-responder | 4 Participants |
Primary
Dose-limiting Toxicity (DLT) - Arm B
Frequency of dose-limiting toxicities (DLTs) by dose cohort.
Time frame: Cycle 1 Day 1 - Cycle 1 Day 36
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Arm A: | Dose-limiting Toxicity (DLT) - Arm B | 0 Participants |
| Arm B: Regimen 1: | Dose-limiting Toxicity (DLT) - Arm B | 0 Participants |
| Arm B: Regimen 2: | Dose-limiting Toxicity (DLT) - Arm B | 0 Participants |
| Arm B: Regimen 3: | Dose-limiting Toxicity (DLT) - Arm B | 0 Participants |
Secondary
Antidrug Antibodies (ADAs) - Arm A and Arm B
Development of human antidrug antibodies (ADAs) against Vilobelimab. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months.
Time frame: Up to 27 months
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm A: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients with at least one positive result | 2 Participants |
| Arm A: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients without positive result | 8 Participants |
| Arm B: Regimen 1: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients without positive result | 3 Participants |
| Arm B: Regimen 1: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients with at least one positive result | 0 Participants |
| Arm B: Regimen 2: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients with at least one positive result | 0 Participants |
| Arm B: Regimen 2: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients without positive result | 6 Participants |
| Arm B: Regimen 3: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients with at least one positive result | 0 Participants |
| Arm B: Regimen 3: | Antidrug Antibodies (ADAs) - Arm A and Arm B | Patients without positive result | 6 Participants |
Secondary
Disease Control Rate - Arm A and Arm B
Disease control rate is defined as the relative number of patients achieving stable disease (SD/iSD), CR/iCR or PR/iPR according to modified RECIST v1.1 (including clinical response)/iRECIST response.
Time frame: Up to 36 months
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No response assessment | 8 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No response assessment | 8 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No controlled disease | 6 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No response assessment | 8 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | EOT Visit | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No response assessment | 10 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No response assessment | 10 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No response assessment | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | EOT Visit | No response assessment | 7 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No response assessment | 9 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | Controlled disease | 2 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | Controlled disease | 1 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No response assessment | 10 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | EOT Visit | No controlled disease | 3 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | Controlled disease | 0 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No response assessment | 8 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No response assessment | 8 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No response assessment | 10 Participants |
| Arm A: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | EOT Visit | No controlled disease | 2 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No controlled disease | 1 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No response assessment | 2 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | EOT Visit | Controlled disease | 0 Participants |
| Arm B: Regimen 1: | Disease Control Rate - Arm A and Arm B | EOT Visit | No response assessment | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | Controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No response assessment | 6 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No response assessment | 6 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No controlled disease | 2 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No response assessment | 4 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | EOT Visit | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No response assessment | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | EOT Visit | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | Controlled disease | 3 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No response assessment | 6 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | EOT Visit | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 2: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No response assessment | 4 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 11 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 5 Day 1 | Controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No response assessment | 3 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No response assessment | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | EOT Visit | No controlled disease | 3 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | No controlled disease | 1 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 12 Day 29 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 4 Day 1 | Controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 13 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | No controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | EOT Visit | No response assessment | 3 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 29 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 17 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 14 Day 15 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No response assessment | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | No controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 7 Day 1 | Controlled disease | 1 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No controlled disease | 1 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 15 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 8 Day 1 | No response assessment | 5 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No response assessment | 4 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | EOT Visit | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 9 Day 1 | No response assessment | 6 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 16 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | Controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 6 Day 1 | Controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 3 Day 1 | Controlled disease | 2 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 10 Day 1 | No controlled disease | 0 Participants |
| Arm B: Regimen 3: | Disease Control Rate - Arm A and Arm B | Cycle 2 Day 1 | Controlled disease | 4 Participants |
Secondary
Overall Survival (OS)- Arm A and Arm B
Overall survival is defined as the time from first study treatment administration to death. Patients alive when they discontinue the study are censored at their last recorded date of being alive.
Time frame: Up to 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: | Overall Survival (OS)- Arm A and Arm B | 285.0 days |
| Arm B: Regimen 1: | Overall Survival (OS)- Arm A and Arm B | 106.0 days |
| Arm B: Regimen 2: | Overall Survival (OS)- Arm A and Arm B | 300.5 days |
| Arm B: Regimen 3: | Overall Survival (OS)- Arm A and Arm B | NA days |
Secondary
Plasma Concentration of Vilobelimab - Arm A and Arm B
The plasma concentration of vilobelimab was assessed at different time points pre- and post-dose. The post-dose Cycle 1 Day 22 values correspond to Cmax and the pre-dose Cycle 1 Day 8, pre-dose Cycle 1 Day 22, pre-dose Cycle 2 Day 1 and per-dose Cycle 5 Day 1 values to Ctrough. In contrast to the time frame of the secondary efficacy outcome measures (3.-5., 7.-8), which were reported until EOS (up to 36 months), the time frames of ADAs (6.) and PK (9.) are measured (only) until first FU. Therefore, the time frame is different, i.e. 24 months of treatment until EOT + (approx.) 12 weeks/3 months until first FU up to 27 months.
Time frame: Up to 27 months
Population: Not all patients are analyzed at each visit as the values for these patients are missing. This reason for this is either that the values for these patients are missing in the data or that these patients have already discontinued the study.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 5 Day 1 | 107989.9 ng/mL | Geometric Coefficient of Variation 43.6 |
| Arm A: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 8 | 128404.2 ng/mL | Geometric Coefficient of Variation 86.8 |
| Arm A: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Post-dose Cycle 1 Day 22 | 514953.9 ng/mL | Geometric Coefficient of Variation 43.5 |
| Arm A: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 2 Day 1 | 81260.1 ng/mL | Geometric Coefficient of Variation 281.2 |
| Arm A: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 22 | 85088.6 ng/mL | Geometric Coefficient of Variation 135.8 |
| Arm B: Regimen 1: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Post-dose Cycle 1 Day 22 | 208865.8 ng/mL | Geometric Coefficient of Variation 27.6 |
| Arm B: Regimen 1: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 8 | 32488.5 ng/mL | Geometric Coefficient of Variation 51.9 |
| Arm B: Regimen 1: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 22 | 25312.8 ng/mL | Geometric Coefficient of Variation 94.1 |
| Arm B: Regimen 1: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 2 Day 1 | 11124.0 ng/mL | — |
| Arm B: Regimen 2: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 22 | 72792.5 ng/mL | Geometric Coefficient of Variation 57.5 |
| Arm B: Regimen 2: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Post-dose Cycle 1 Day 22 | 261068.1 ng/mL | Geometric Coefficient of Variation 96.7 |
| Arm B: Regimen 2: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 2 Day 1 | 48722.9 ng/mL | Geometric Coefficient of Variation 106.9 |
| Arm B: Regimen 2: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 8 | 80525.0 ng/mL | Geometric Coefficient of Variation 41.5 |
| Arm B: Regimen 2: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 5 Day 1 | 132497.0 ng/mL | — |
| Arm B: Regimen 3: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 22 | 78248.6 ng/mL | Geometric Coefficient of Variation 48.6 |
| Arm B: Regimen 3: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 2 Day 1 | 80697.1 ng/mL | Geometric Coefficient of Variation 104.1 |
| Arm B: Regimen 3: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Post-dose Cycle 1 Day 22 | 210169.5 ng/mL | Geometric Coefficient of Variation 66.1 |
| Arm B: Regimen 3: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 1 Day 8 | 88749.9 ng/mL | Geometric Coefficient of Variation 52.4 |
| Arm B: Regimen 3: | Plasma Concentration of Vilobelimab - Arm A and Arm B | Pre-dose Cycle 5 Day 1 | 41506.4 ng/mL | Geometric Coefficient of Variation 65.9 |
Secondary
Progression-free Survival (PFS)- Arm A and Arm B
PFS is defined as the time from first study treatment administration to progression (i.e. PD, iUPD, iCPD) or death. Patients without progression are censored at their last visit/study treatment administration.
Time frame: Up to 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: | Progression-free Survival (PFS)- Arm A and Arm B | 50.0 days |
| Arm B: Regimen 1: | Progression-free Survival (PFS)- Arm A and Arm B | 106.0 days |
| Arm B: Regimen 2: | Progression-free Survival (PFS)- Arm A and Arm B | 90.0 days |
| Arm B: Regimen 3: | Progression-free Survival (PFS)- Arm A and Arm B | 87.5 days |
Secondary
Quality of Life (QoL) - Arm A and Arm B
The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 version 3.0 measures the different aspects that define the quality of life of cancer patients or survivors. The reported total score ranges from 0 to 100 whereas a higher score represents a higher response level. The total score was calculated as mean of all 15 single scores. It was only calculated if all 15 single scores were non-missing (for more information see Fayers PM, Aaronson NK, Bjordal K, Groenvold M, Curran D, Bottomley A, on behalf of the EORTC Quality of Life Group. The EORTC QLQ-C30 Scoring Manual (3rd Edition). Published by: European Organisation for Research and Treatment of Cancer, Brussels 2001.). The absolute changes from baseline are presented.
Time frame: Up to 36 months
Population: Not all patients are analyzed at each visit as the values for these patients are missing. This reason for this is either that the values for these patients are missing in the data or that these patients have already discontinued the study.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 7 Day 1 | 2.55 units on a scale | Standard Deviation 1.63 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 13 Day 1 | 1.00 units on a scale | Standard Deviation 5.09 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 8 Day 1 | -2.10 units on a scale | Standard Deviation 8.2 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 4 Day 1 | 1.95 units on a scale | Standard Deviation 0.21 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 12 Day 1 | 0.60 units on a scale | Standard Deviation 7.21 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 9 Day 1 | -2.10 units on a scale | Standard Deviation 12.02 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 2 Day 1 | 0.31 units on a scale | Standard Deviation 4.38 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | EOT Visit | -1.67 units on a scale | Standard Deviation 3.91 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 10 Day 1 | 0.20 units on a scale | Standard Deviation 7.78 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 15 Day 1 | 4.60 units on a scale | — |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 11 Day 1 | -0.75 units on a scale | Standard Deviation 8.27 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 5 Day 1 | -1.15 units on a scale | Standard Deviation 2.19 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 3 Day 1 | -0.35 units on a scale | Standard Deviation 5.73 |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 14 Day 1 | 4.60 units on a scale | — |
| Arm A: | Quality of Life (QoL) - Arm A and Arm B | Cycle 6 Day 1 | 0.75 units on a scale | Standard Deviation 0.49 |
| Arm B: Regimen 1: | Quality of Life (QoL) - Arm A and Arm B | EOT Visit | 0.80 units on a scale | — |
| Arm B: Regimen 1: | Quality of Life (QoL) - Arm A and Arm B | Cycle 2 Day 1 | -0.80 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 13 Day 1 | -3.50 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 2 Day 1 | -2.68 units on a scale | Standard Deviation 3.58 |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 3 Day 1 | 3.00 units on a scale | Standard Deviation 5.66 |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 4 Day 1 | -2.40 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 5 Day 1 | -3.80 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 6 Day 1 | -1.40 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 7 Day 1 | 1.20 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 8 Day 1 | -0.70 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 9 Day 1 | -3.40 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 10 Day 1 | -1.10 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 12 Day 1 | -2.30 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 14 Day 1 | -4.00 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 15 Day 1 | 0.20 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 16 Day 1 | -5.10 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | Cycle 17 Day 1 | -2.30 units on a scale | — |
| Arm B: Regimen 2: | Quality of Life (QoL) - Arm A and Arm B | EOT Visit | 1.13 units on a scale | Standard Deviation 4.14 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 4 Day 1 | -6.35 units on a scale | Standard Deviation 0.78 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 3 Day 1 | -3.27 units on a scale | Standard Deviation 1.62 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 8 Day 1 | -3.40 units on a scale | — |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 2 Day 1 | -3.04 units on a scale | Standard Deviation 6.21 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 7 Day 1 | -3.50 units on a scale | — |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 6 Day 1 | -1.85 units on a scale | Standard Deviation 2.33 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | Cycle 5 Day 1 | -3.20 units on a scale | Standard Deviation 2.83 |
| Arm B: Regimen 3: | Quality of Life (QoL) - Arm A and Arm B | EOT Visit | -4.67 units on a scale | Standard Deviation 6.53 |
Secondary
Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B
Duration of stable disease is defined as the time from first diagnosis of response or stable disease (i.e., CR/iCR/PR/iPR/SD/iSD) to progression (i.e. progressive disease (PD), unconfirmed progressive disease according to iRECIST (iUPD), confirmed progressive disease (iCPD)) or death. Responding and stable patients without progression are censored at their last visit/study treatment administration. Patients who never respond or have a stable disease are excluded from this analysis.
Time frame: Up to 36 months
Population: Only patients with response were analyzed. As in Arm B: Regimen 1: there was no patient with a response, the overall number of participants analyzed is 0.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm A: | Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B | 490.0 days |
| Arm B: Regimen 2: | Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B | NA days |
| Arm B: Regimen 3: | Response (Complete Response (CR) / CR According to iRECIST (iCR) / Partial Response (PR) / PR According to iRECIST (iPR)) and Stable Disease (SD) Duration - Arm A and Arm B | 128.0 days |