Advanced Solid Tumor
Conditions
Brief summary
AFM24-101 is a first in human Phase 1/2a open-label, non-randomized, multi-center, multiple ascending dose escalation/expansion study evaluating AFM24 as monotherapy in patients with advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies. AFM24 is a tetravalent bispecific (anti-human EGFR x anti-human CD16A) innate immune cell engaging recombinant antibody being developed to target EGFR-expressing solid tumors and has been designed to specifically utilize the cytotoxic potential of the innate immune system, in particular natural killer cells and macrophages for the specific and efficient elimination of EGFR expressing cancer cells.
Detailed description
There will be two parts to this study: a dose escalation phase (1) and a dose expansion phase (2a). The aim of the dose escalation phase is to determine the maximum tolerated dose (MTD) and establish the recommended Phase 2a dose (RP2D). The dose escalation phase will be followed by the dose expansion phase once the MTD/RP2D of AFM24 monotherapy has been determined. The dose expansion phase of the study using the MTD/P2D is intended to collect preliminary evidence of efficacy and to further confirm the safety of AFM24 as a monotherapy. The expansion phase will have 3 arms based on tumor type. * Renal cell carcinoma(clear cell), failing standard of care (SoC) that includes TKIs and PD1 targeted therapy * Non-small cell lung cancer (EGFR-mut), failing SoC TKIs * Colorectal cancer, failing SOC chemotherapy, VEGF(R) and EGFR targeted antibodies
Interventions
DRUG14 mg AFM24
14 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG40 mg AFM24
40 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG80 mg AFM24
80 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG160 mg AFM24
160 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG320 mg AFM24
320 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG480 mg AFM24
480 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
DRUG720 mg AFM24
720 milligram AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle.
Sponsors
Affimed GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adequate organ function * Phase 1: Histologically or cytologically confirmed advanced or metastatic solid malignancies that are known to express EGFR * Phase 1: Previously treated with ≥ 1 lines of anticancer therapy and have documented disease progression during or after their most recent line of anticancer therapy. In addition, either there is no further SOC therapy for the patient or the remaining SOC therapies are deemed not appropriate for the patient by the Investigator. * Phase 1: Patients must have at least one tumor site that is accessible to biopsy * Phase 2a: Measurable disease per RECIST 1.1 * Phase 2a: Histologically confirmed advanced or metastatic EGFR+ malignancies for each expansion cohorts: * Colorectal Cancer (MSS), KRAS-wildtype: disease has progressed after ≥ 2 prior lines of therapy which must have included oxaliplatin, fluoropyrimidine, bevacizumab, and an anti-EGFR therapy * ccRCC: disease has progressed after ≥ 2 prior lines of therapy which must have included a TKI and a checkpoint inhibitor * metastatic NSCLC, EGFRmut: disease has progressed on/after after ≥ 1 prior lines of therapy for advanced disease including ≥ 1 prior TKI approved for EGFR mut NSCLC
Exclusion criteria
* Treatment with systemic anticancer therapy within 4 weeks of the first dose of study drug (6 weeks if therapy was mitomycin C and/or nitrosoureas), or within 5 half-lives of the agent if half-life is known and it is shorter, before first dose of study drug. Anticancer therapies include cytotoxic chemotherapy, targeted inhibitors, and immunotherapies, but do not include hormonal therapy or radiotherapy. * Radiation therapy within 2 weeks before 1st dose of study drug or unresolved toxicity from previous radiotherapy. * History of any other malignancy known to be active, with the exception of completely removed in situ cervical intra-epithelial neoplasia, non-melanoma skin cancer, DCIS, early stage prostate cancer that has been adequately treated, and other cancers from which the patient has been disease free for 3 years or longer. * Currently participating in a study and receiving study therapy, or participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | During Cycle 1 (up to 28 days) | The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 (Cycle 1). |
| Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) | Up to approximately 16 weeks. | Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22. | Area under the concentration-time curve from time 0 to time tau (7 days) of AFM24 in plasma (AUC0-168) |
| Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 8. | Maximum measured concentration (Cmax) of AFM24 in plasma |
| Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22. | First time to maximum observed concentration of AFM24 sampled during a dosing interval. |
| Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 22. | Minimum measured concentration (Cmin) of AFM24 in plasma |
| Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 39 weeks. | The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study. |
| Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks. | Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment by local reader. |
| Phase 1: Duration of Response Rate (DOR) | through study completion (estimated up to 24 weeks) | The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). |
| Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks. | Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. |
| Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs). |
| Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks. | Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs). |
| Phase 2a: Trough Concentration (Ctrough) of AFM24 | Pre-dose (2 hours maximum) on Cycle 1 Day 22. | Trough concentration (Ctrough) of AFM24 in plasma. |
| Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24 | Pre-dose (2 hours maximum) on Cycle 1 Day 22 and at end of infusion (EOI) on Cycle 1 Day 22. | Maximum measured concentration (Cmax) of AFM24 in plasma. |
| Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24 | Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 101 weeks. | The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study. |
| Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1 | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Overall response as defined by achieving confirmed CR and/or PR assessed by Central Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment. |
| Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Local Review | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessments by local reader used only. |
| Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Central Review | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessment by central reader used only. |
| Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease control was assessed by local RECIST v1.1 and by central RECIST v1.1. |
| Phase 2a: Progression-free-survival (PFS) | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. PFS was measured by local and central assessments. |
| Phase 2a: Overall Survival | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Overall Survival (OS) was defined as (date of death - date of first dose)/30.4375. Patients alive at the end of study will be censored on the last date of observation. |
| Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs) | From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks. | Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs). |
| Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks. | Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs). |
Countries
Germany, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
This study was a phase 1/2a open-label, multicenter study to assess the safety, tolerability, pharmacokinetics and preliminary efficacy of AFM24 in patients with advanced solid cancers
Pre-assignment details
Phase 1 subjects enrolled if they had a tumor known to express Epidermal Growth Factor Receptor (EGFR), Phase 2 subjects were screened for positive EGFR from tumor site. Specialists assessed the subjects, and they were enrolled in the study if they met all inclusion criteria and none of the exclusion criteria.
Participants by arm
| Arm | Count |
|---|---|
| Phase 1- 14 mg Cohort 1 Subjects, with tumors known to express EGFR, who received 14 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 2 |
| Phase 1- 40 mg Cohort 2 Subjects, with tumors known to express EGFR, who received 40 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 6 |
| Phase 1- 80 mg Cohort 3 Subjects, with tumors known to express EGFR, who received 80 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 4 |
| Phase 1- 160 mg Cohort 4 Subjects, with tumors known to express EGFR, who received 160 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 5 |
| Phase 1- 320 mg Cohort 5 Subjects, with tumors known to express EGFR, who received 320 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 6 |
| Phase 1- 480 mg Cohort 6 Subjects, with tumors known to express EGFR, who received 480 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. | 6 |
| Phase 1- 720 mg Cohort 7 Subjects, with tumors known to express EGFR, who received 720 milligram (mg) AFM24 on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing). | 6 |
| Phase 2- CRC 480 mg Cohort A Subjects with microsatellite stable (MSS) colorectal cancer (CRC) with rat sarcoma gene (RAS) wild-type tumor expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing). | 19 |
| Phase 2- ccRCC 480 mg Cohort B Subjects with clear cell renal cell carcinoma (ccRCC) expressing EGFR who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing). | 8 |
| Phase 2- NSCLC 480 mg Cohort C Subjects with advanced or metastatic (non-small cell lung cancer) NSCLC with an epidermal growth factor receptor (EGFR) mutation who received 480 milligram (mg) AFM24 weekly on Day 1, Day 8, Day 15, and Day 22 of a 28-day cycle. A dose could be given over two days (split day dosing). | 23 |
| Total | 85 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse event/ Toxicity | 0 | 3 | 0 | 1 | 0 | 0 | 0 | 1 | 0 | 3 |
| Overall Study | Death | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 |
| Overall Study | Disease progression | 2 | 3 | 4 | 4 | 6 | 6 | 6 | 15 | 6 | 18 |
| Overall Study | Other than listed | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1- 14 mg Cohort 1 | Phase 1- 40 mg Cohort 2 | Phase 1- 80 mg Cohort 3 | Phase 1- 160 mg Cohort 4 | Phase 1- 320 mg Cohort 5 | Phase 1- 480 mg Cohort 6 | Phase 1- 720 mg Cohort 7 | Phase 2- CRC 480 mg Cohort A | Phase 2- ccRCC 480 mg Cohort B | Phase 2- NSCLC 480 mg Cohort C | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 73.0 Years STANDARD_DEVIATION 0 | 54.7 Years STANDARD_DEVIATION 14.12 | 47.3 Years STANDARD_DEVIATION 20.89 | 58.4 Years STANDARD_DEVIATION 11.35 | 57.7 Years STANDARD_DEVIATION 16.99 | 59.7 Years STANDARD_DEVIATION 12.08 | 53.8 Years STANDARD_DEVIATION 10.57 | 62.7 Years STANDARD_DEVIATION 9.32 | 67.1 Years STANDARD_DEVIATION 15 | 61.1 Years STANDARD_DEVIATION 11.83 | 60.2 Years STANDARD_DEVIATION 12.8 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 1 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 2 Participants | 3 Participants | 3 Participants | 5 Participants | 6 Participants | 6 Participants | 18 Participants | 7 Participants | 21 Participants | 73 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 1 Participants | 10 Participants | 1 Participants | 18 Participants | 32 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race (NIH/OMB) White | 1 Participants | 4 Participants | 4 Participants | 4 Participants | 4 Participants | 5 Participants | 5 Participants | 9 Participants | 7 Participants | 5 Participants | 48 Participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 0 Participants | 4 Participants | 3 Participants | 2 Participants | 1 Participants | 5 Participants | 2 Participants | 10 Participants | 29 Participants |
| Sex: Female, Male Male | 1 Participants | 5 Participants | 4 Participants | 1 Participants | 3 Participants | 4 Participants | 5 Participants | 14 Participants | 6 Participants | 13 Participants | 56 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 6 / 6 | 4 / 4 | 3 / 5 | 4 / 6 | 4 / 6 | 6 / 6 | 14 / 19 | 6 / 8 | 7 / 23 |
| other Total, other adverse events | 2 / 2 | 5 / 6 | 4 / 4 | 5 / 5 | 6 / 6 | 6 / 6 | 6 / 6 | 19 / 19 | 8 / 8 | 22 / 23 |
| serious Total, serious adverse events | 2 / 2 | 3 / 6 | 2 / 4 | 2 / 5 | 4 / 6 | 3 / 6 | 2 / 6 | 8 / 19 | 6 / 8 | 8 / 23 |
Outcome results
Primary
Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1
The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) v5.0. DLT is defined as an adverse event (AE) or abnormal laboratory value assessed as unrelated to underlying disease, disease progression, inter-current illness, or concomitant medications, that occurs ≤28 days following the first dose of AFM24 (Cycle 1).
Time frame: During Cycle 1 (up to 28 days)
Population: The Dose-Determining Set (DDS): All patients in the safety set (all patients who received at least one dose of AFM24), who had either (a) experienced DLT at any time during Cycle 1, or (b) met the minimum safety evaluation requirements without experiencing DLT within Cycle 1.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 1 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: The Number of Subjects With Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
Primary
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR])
Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment.
Time frame: Up to approximately 16 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) | 0 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) | 0 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) | 2 Participants |
Secondary
Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma
Area under the concentration-time curve from time 0 to time tau (7 days) of AFM24 in plasma (AUC0-168)
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
Population: The Pharmacokinetic set: all subjects who received at least one adequately documented dose of study drug and had at least one adequately documented post dose pharmacokinetic (PK) measurement. Subjects were excluded if they did not have at least two quantifiable concentration values, two of which must have occurred after Tmax, this was the case for one subject in Cohort 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 53400 hours*nanogram /milliLiter | Standard Deviation 61700 |
| Phase 1- 40 mg Cohort 2 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 549000 hours*nanogram /milliLiter | Standard Deviation 254000 |
| Phase 1- 80 mg Cohort 3 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 1290000 hours*nanogram /milliLiter | Standard Deviation 395000 |
| Phase 1- 160 mg Cohort 4 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 4940000 hours*nanogram /milliLiter | Standard Deviation 1370000 |
| Phase 1- 320 mg Cohort 5 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 18100000 hours*nanogram /milliLiter | Standard Deviation 6120000 |
| Phase 1- 480 mg Cohort 6 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 28700000 hours*nanogram /milliLiter | Standard Deviation 7620000 |
| Phase 1- 720 mg Cohort 7 | Phase 1: Area Under the Concentration-time Curve From Time 0 to Time Tau (7 Days) of AFM24 in Plasma | 40200000 hours*nanogram /milliLiter | Standard Deviation 12000000 |
Secondary
Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))
Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 0 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 1 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 0 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 0 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 0 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 2 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | 1 Participants |
Secondary
Phase 1: Duration of Response Rate (DOR)
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs).
Time frame: through study completion (estimated up to 24 weeks)
Population: No subjects had a response.
Secondary
Phase 1: Maximum Plasma Concentration (Cmax) of AFM24
Maximum measured concentration (Cmax) of AFM24 in plasma
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 8.
Population: The Pharmacokinetic set: all subjects who received at least one adequately documented dose of study drug and had at least one adequately documented post dose PK measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 3290 nanogram /milliLiter | Standard Deviation 2860 |
| Phase 1- 40 mg Cohort 2 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 13200 nanogram /milliLiter | Standard Deviation 3100 |
| Phase 1- 80 mg Cohort 3 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 29200 nanogram /milliLiter | Standard Deviation 6620 |
| Phase 1- 160 mg Cohort 4 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 60900 nanogram /milliLiter | Standard Deviation 17600 |
| Phase 1- 320 mg Cohort 5 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 204000 nanogram /milliLiter | Standard Deviation 55600 |
| Phase 1- 480 mg Cohort 6 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 298000 nanogram /milliLiter | Standard Deviation 71100 |
| Phase 1- 720 mg Cohort 7 | Phase 1: Maximum Plasma Concentration (Cmax) of AFM24 | 354000 nanogram /milliLiter | Standard Deviation 104000 |
Secondary
Phase 1: Minimum Plasma Concentration (Cmin) of AFM24
Minimum measured concentration (Cmin) of AFM24 in plasma
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 1 and on pre-dose (2 hours maximum) Cycle 1 Day 22.
Population: The Pharmacokinetic set: all subjects who received at least one adequately documented dose of study drug and had at least one adequately documented post dose PK measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 32.7 ng/mL | Standard Deviation 46.2 |
| Phase 1- 40 mg Cohort 2 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 311 ng/mL | Standard Deviation 281 |
| Phase 1- 80 mg Cohort 3 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 810 ng/mL | Standard Deviation 482 |
| Phase 1- 160 mg Cohort 4 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 12000 ng/mL | Standard Deviation 3540 |
| Phase 1- 320 mg Cohort 5 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 73800 ng/mL | Standard Deviation 40600 |
| Phase 1- 480 mg Cohort 6 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 117000 ng/mL | Standard Deviation 49600 |
| Phase 1- 720 mg Cohort 7 | Phase 1: Minimum Plasma Concentration (Cmin) of AFM24 | 233000 ng/mL | Standard Deviation 113000 |
Secondary
Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR))
Overall response as defined by achieving confirmed CR and/or PR assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment by local reader.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: Overall Response Rate (Complete Response (CR) + Partial Response (PR)) | 0 Participants |
Secondary
Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24
The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study.
Time frame: Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 39 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 1 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 4 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 2 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 3 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 1 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 0 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) and Neutralizing ADAs During Treatment With AFM24 | 1 Participants |
Secondary
Phase 1: The Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 2 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 3 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 2 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 2 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 4 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 3 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: The Number of Subjects With Serious Adverse Events (SAEs) | 2 Participants |
Secondary
Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 43 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 2 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 4 Participants |
| Phase 1- 160 mg Cohort 4 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 5 Participants |
| Phase 1- 320 mg Cohort 5 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1- 480 mg Cohort 6 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
| Phase 1- 720 mg Cohort 7 | Phase 1: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 6 Participants |
Secondary
Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24
First time to maximum observed concentration of AFM24 sampled during a dosing interval.
Time frame: Pre-dose (2 hours maximum) and 15, 30, 45 min after start of infusion (SOI) and end of infusion (EOI) and 1, 4, 18, 24, 48, 144 hours after EOI on Cycle 1 Day 22.
Population: The Pharmacokinetic set: all subjects who received at least one adequately documented dose of study drug and had at least one adequately documented post dose PK measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 1.84 hours | Standard Deviation 1.19 |
| Phase 1- 40 mg Cohort 2 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 3.43 hours | Standard Deviation 1.97 |
| Phase 1- 80 mg Cohort 3 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 5.63 hours | Standard Deviation 1.71 |
| Phase 1- 160 mg Cohort 4 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 5.64 hours | Standard Deviation 1.3 |
| Phase 1- 320 mg Cohort 5 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 7.18 hours | Standard Deviation 0.564 |
| Phase 1- 480 mg Cohort 6 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 7.52 hours | Standard Deviation 1.38 |
| Phase 1- 720 mg Cohort 7 | Phase 1: Time of Maximum Observed Concentration (Tmax) of AFM24 | 5.21 hours | Standard Deviation 0.28 |
Secondary
Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD))
Disease control as defined by achieving CR and/or PR and/or SD assessed by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Disease control was assessed by local RECIST v1.1 and by central RECIST v1.1.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Local RECIST v1.1 | 2 Participants |
| Phase 1- 14 mg Cohort 1 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Central RECIST v1.1 | 1 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Local RECIST v1.1 | 2 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Central RECIST v1.1 | 0 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Local RECIST v1.1 | 9 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Disease Control Rate (Complete Response (CR) + Partial Response (PR) +Stable Disease (SD)) | Central RECIST v1.1 | 2 Participants |
Secondary
Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Central Review
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessment by central reader used only.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: All patients who received at least one dose of AFM24 and who had a response by RECIST v1.1 by Central Review.
Secondary
Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Local Review
The DOR defined as time from first assessment of partial response (PR) or complete response (CR) to follow-on first assessment of progressive disease will be summarized by descriptive statistics including median DOR and where appropriate the respective 95% confidence intervals (CIs). Assessments by local reader used only.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: All patients who received at least one dose of AFM24 and who had a response by RECIST v1.1 by Local Review.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Duration of Response Rate (DOR) by RECIST v1.1 by Local Review | NA Months |
Secondary
Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24
Maximum measured concentration (Cmax) of AFM24 in plasma.
Time frame: Pre-dose (2 hours maximum) on Cycle 1 Day 22 and at end of infusion (EOI) on Cycle 1 Day 22.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24 | 254285.7 ng/mL (nanogram/milliliter) | Standard Deviation 145002.08 |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24 | 170428.6 ng/mL (nanogram/milliliter) | Standard Deviation 71327.55 |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Maximum Plasma Concentration (Cmax) of AFM24 | 272111.1 ng/mL (nanogram/milliliter) | Standard Deviation 111029.35 |
Secondary
Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1
Overall response as defined by achieving confirmed CR and/or PR assessed by Central Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Partial or complete response needs to be confirmed with repeated assessment at least 4 weeks after the initial assessment.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1 | 0 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1 | 0 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Overall Response Rate (Complete Response [CR] + Partial Response [PR]) Assessed by Central RECIST v1.1 | 0 Participants |
Secondary
Phase 2a: Overall Survival
Overall Survival (OS) was defined as (date of death - date of first dose)/30.4375. Patients alive at the end of study will be censored on the last date of observation.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Overall Survival | 6.64 Months |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Overall Survival | 8.87 Months |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Overall Survival | NA Months |
Secondary
Phase 2a: Progression-free-survival (PFS)
Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. PFS was measured by local and central assessments.
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Progression-free-survival (PFS) | Local RECIST v1.1 | 1.61 Months |
| Phase 1- 14 mg Cohort 1 | Phase 2a: Progression-free-survival (PFS) | Central RECIST v1.1 | 3.88 Months |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Progression-free-survival (PFS) | Local RECIST v1.1 | 2.55 Months |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Progression-free-survival (PFS) | Central RECIST v1.1 | 8.15 Months |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Progression-free-survival (PFS) | Local RECIST v1.1 | 3.68 Months |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Progression-free-survival (PFS) | Central RECIST v1.1 | 3.52 Months |
Secondary
Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24
The number of subjects who developed anti-drug antibodies (ADAs) at any time during the study.
Time frame: Pre-dose cycle 1 Day 1 and end of treatment, up to approximately 101 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24 | 3 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24 | 1 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: The Number of Subjects Who Developed Anti-drug Antibodies (ADAs) During Treatment With AFM24 | 8 Participants |
Secondary
Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs)
Serious adverse Events (SAEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs) | 8 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs) | 6 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: The Number of Subjects With Serious Adverse Events (SAEs) | 8 Participants |
Secondary
Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs)
Adverse Events (AEs) will be summarized with patient counts by Medical Dictionary for Regulatory Activities (MedDRA) System Organ Classes (SOCs) and Preferred Terms (PTs).
Time frame: From the start of first infusion till the last infusion + 30 days, up to approximately 105 weeks.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 19 Participants |
| Phase 1- 40 mg Cohort 2 | Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 8 Participants |
| Phase 1- 80 mg Cohort 3 | Phase 2a: The Number of Subjects With Treatment-emergent Adverse Events (TEAEs) | 23 Participants |
Secondary
Phase 2a: Trough Concentration (Ctrough) of AFM24
Trough concentration (Ctrough) of AFM24 in plasma.
Time frame: Pre-dose (2 hours maximum) on Cycle 1 Day 22.
Population: The safety set: All patients who received at least one dose of AFM24.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1- 14 mg Cohort 1 | Phase 2a: Trough Concentration (Ctrough) of AFM24 | 69155.7 ng/mL (nanogram/milliliter) | Standard Deviation 32573.34 |
| Phase 1- 40 mg Cohort 2 | Phase 2a: Trough Concentration (Ctrough) of AFM24 | 77642.7 ng/mL (nanogram/milliliter) | Standard Deviation 79113.19 |
| Phase 1- 80 mg Cohort 3 | Phase 2a: Trough Concentration (Ctrough) of AFM24 | 84616.7 ng/mL (nanogram/milliliter) | Standard Deviation 36176.09 |