Advanced Solid Tumor
Conditions
Brief summary
AFM24-102 is a Phase 1/2a open-label, non-randomized, multicenter, dose escalation, and expansion study evaluating AFM24 in combination with atezolizumab in patients with selected EGRF-expressing advanced solid malignancies whose disease has progressed after treatment with previous anticancer therapies.
Detailed description
There will be 2 parts in this study: a dose escalation phase (phase 1) and an expansion phase (phase 2a). Patients will qualify to receive the investigational drugs (AFM24 + atezolizumab) in the dose escalation phase or the expansion phase only if they are deemed eligible following the safety lead-in phase. Seven days before the planned first combination treatment, patients will receive a single dose of AFM24 and will be observed for any adverse events for 1 week. The aim of the dose escalation phase is to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) of AFM24 in combination with atezolizumab. The dose escalation phase will be followed by the expansion phase once the MTD/RP2D of AFM24 in combination with atezolizumab has been determined. The expansion phase of the study is intended to collect preliminary evidence of efficacy and to further confirm the safety of AFM24 in combination with atezolizumab. The tumor types planned to be studied in the AFM24/atezolizumab combination study will be: * Non-small cell lung cancer (EGFR-WT), with disease progression after chemotherapy and PD1/PD-L1 targeted therapy * Gastric/GEJ cancer if intolerant to or with disease progression after standard platinum-based chemotherapy * Pancreatic/hepatocellular/biliary tract cancer with disease progression after standard of care (SOC) therapy or if there is no appropriate SOC available for their condition * Advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation with disease progression on or after received ≥1 prior lines of treatment for advanced disease, including a Tyrosine-Kinase Inhibitor (TKI) for EGFR mutations
Interventions
DRUGAFM24
intravenous infusion
intravenous infusion
Sponsors
Affimed GmbH
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically or cytologically confirmed advanced or metastatic EGFR-positive selected cancer types (except for NSCLC) * Advanced or metastatic NSCLC, EGFR WT: disease has progressed after ≥ 1 prior lines of therapy which must have included a platinum-based doublet in combination with PD1/PD-L1 antibody or must have received an anti-PD1/PD-L1 antibody prior to or after a platinum-based doublet * Advanced, unresectable, or metastatic gastric/GEJ adenocarinoma: after ≥ 1 prior chemotherapy regimen including a platinum and fluoropyrimidine doublet * Advanced or metastatic HCC (BCLC C or B not amenable or refractory to locoregional therapy), hepatobiliary-, or pancreatic adenocarcinoma: after ≥1 prior line of an approved SOC therapy for the respective disease type or to whom the available SOC is not appropriate in the opinion of the investigator * Advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation and whose disease has progressed on or after having received ≥ prior TKI approved for EGFR mutated NSCLC. Subjects treated with a 1st or 2nd generation TKI in 1st line who developed a documented T790M mutation must have received a TKI targeting this mutation such as Osimertinib or Lazertinib to be eligible. Subjects must have documentation of EGFR mutated NSCLC as assessed by an approved test using genomic sequencing of tumor or circulation free tumor DNA. The patients should have received a 2nd line of treatment if approved and available or may be enrolled in the study if in the opinion of the investigator it is in the patient's best interest,or the SOC is not appropriate. * Adequate organ function * Phase 1: Evaluable or measurable disease per RECIST v1.1 * Phase 2a: Measurable disease per RECIST v1.1
Exclusion criteria
* Treatment with systemic anticancer therapy including investigational agent within 4 weeks of the first dose of study drug, 6 weeks for mitomycin C or nitrosoureas, 2 weeks (or 5 half-lives whichever is longer) for using fluorouracil or small molecule targeted drugs, 2 weeks for using traditional Chinese medicine with anti-tumor indication. * 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 active in any other clinical study, or administration of other investigational agent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 | During cycle 1 (each cycle has 28 days) | The number of patients with dose limiting toxicities (DLTs) in the first cycle, as assessed by the National Cancer Institute Common Technology Criteria for Adverse Events (CTCAE) v5.0 |
| Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks. | Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetics (PK) of AFM24 | During cycle 1 (each cycle has 28 days) | Maximum plasma concentration (Cmax) on Cycle 1 Day 22 |
| Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | Ph 1 within 2h prior to: each drug intake (Cycle 1), 1st + 3rd drug intake (Cycle 2 onwards) and at EOT, up to 27 weeks. Ph 2a within 2h prior to: 1st drug intake (Cycle 1 and Cycle 3 onwards), 1st + 3rd drug intake (Cycle 2) and at EOT, up to 97 weeks. | Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab Patients with at least one ADA-positive result at baseline or post-baseline counted as developing anti-drug antibodies (ADAs) against AFM24 |
| Phase 1: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 27 weeks. | Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. |
| Incidence of Patients With TEAEs | From first drug administration up to 30 (non-serious TEAEs) or 56 (serious TEAEs) days after last dose AFM24, until start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approx. 35 (phase 1) and 105 weeks (phase 2a). | Number of patients with treatment-emergent adverse events (TEAEs) non-serious or serious |
| Phase 2a: Duration of Response | From the date of first response (unconfirmed) until progression disease assessed by investigator or death. | Duration of Response (DOR) was defined as (date of first progression or death - date of first response (unconfirmed))/30.4375. Patients without response were excluded from the analysis. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator. |
| Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks) | Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks. | Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Clinical benefit rate (CR or PR or SD ≥24 weeks). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1. Best overall response SD counts for Clinical benefit rate if SD ongoing for at least 24 weeks. |
| Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD]) | Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks. | Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Disease Control Rate (CR or PR or SD). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1. |
| Phase 2a: Progression-free Survival | From the first treatment received until the first progression disease assessed by investigator or death. | Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator. |
| Incidence of Patients With SAEs | From first drug administration up to 56 days after the last dose of AFM24, until the start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approximately 35 (phase 1) and 105 weeks (phase 2a). | Number of patients with treatment-emergent serious adverse events (serious TEAEs) |
Countries
Poland, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg Patients aged 18 years or older with documented histologically or cytologically confirmed select advanced or metastatic epidermal growth factor receptor (EGFR)-positive cancers.
The patients received AFM24 160 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 4 |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg Patients aged 18 years or older with documented histologically or cytologically confirmed select advanced or metastatic epidermal growth factor receptor (EGFR)-positive cancers.
The patients received AFM24 480 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 6 |
| Phase 2 - Coh. EXP-1 (EGFR-WT NSCLC) - AFM24 480 mg + Atezolizumab 840 mg Patients aged 18 years or older with advanced or metastatic, EGFR-WT expressing NSCLC whose disease has progressed after having received ≥1 prior lines of therapy for advanced disease. Patients must have received at least a platinum-based doublet in combination with an anti--programmed cell death protein 1 (PD1)/programmed death-ligand 1 (PD-L1) antibody or must have received an anti-PD1/PD-L1 antibody prior to or after a platinum-based doublet. Patients with a known actionable driver mutation (other than EGFR mutation) must have received an approved targeted treatment for the respective mutation. The patients should also have received a second line of treatment if approved and available, or they may be enrolled in the study if in the opinion of the Investigator it is in the patient's best interest, or the standard of care (SOC) is not appropriate.
The patients received AFM24 480 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 49 |
| Phase 2 - Coh. EXP-2 (Gastric or GEJ Adenocarcinoma) - AFM24 480 mg + Atezolizumab 840 mg Patients aged 18 years or older with locally advanced, unresectable, or metastatic gastric or GEJ adenocarcinoma refractory to or, intolerant of, standard therapy. Patients must have received ≥1 prior chemotherapy regimen including a platinum and fluoropyrimidine doublet. The patients should also have received a second line of treatment if approved and available, or they may be enrolled in the study if in the opinion of the Investigator it is in the patient's best interest, or the SOC is not appropriate.
The patients received AFM24 480 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 12 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg Patients aged 18 years or older with advanced or metastatic hepatocellular carcinoma (other than fibrolamellar and sarcomatoid subtype; Barcelona Clinic Liver Cancer Stage C disease or Stage B disease not amenable to locoregional therapy or refractory to locoregional therapy), hepatobiliary-, or pancreatic adenocarcinoma. Patients must have been treated with at least 1 previous line of an approved, SOC therapy for the respective disease type or, in the opinion of the Investigator, available SOC is not appropriate. The patients should also have received a second line of treatment if approved and available, or they may be enrolled in the study if in the opinion of the Investigator it is in the patient's best interest, or the SOC is not appropriate.
The patients received AFM24 480 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 11 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg Patients aged 18 years or older with advanced or metastatic NSCLC harboring a targetable EGFR kinase domain mutation and whose disease has progressed on or after having received ≥1 prior lines of therapy for advanced disease including ≥1 prior tyrosine kinase inhibitor (TKI) approved for EGFR mutated NSCLC, such as gefitinib, erlotinib, afatinib, dacomitinib or osimertinib. Patients who were treated with a 1st or 2nd generation TKI in 1st line and developed a documented T790M mutation must have received a TKI targeting this mutation such as osimertinib or lazertinib to be eligible. Patients must have documentation of EGFR mutated NSCLC as assessed by an approved test using genomic sequencing of tumor or circulating free tumor DNA. The patients should also have received a second line of treatment if approved and available, or they may be enrolled in the study if in the opinion of the Investigator it is in the patient's best interest, or the SOC is not appropriate.
The patients received AFM24 480 mg i.v. qw + atezolizumab 840 mg i.v. q2w in 28-day cycles. AFM24 on Day 1, Day 8, Day 15, and Day 22 (a dose could be given as split day dosing over two days) + atezolizumab on Day 1 and Day 15. | 30 |
| Total | 112 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 | 5 | 0 | 0 | 2 |
| Overall Study | Death | 0 | 0 | 4 | 0 | 0 | 1 |
| Overall Study | Lack of Efficacy | 3 | 5 | 29 | 10 | 11 | 17 |
| Overall Study | Other than listed | 0 | 0 | 9 | 2 | 0 | 8 |
| Overall Study | Physician Decision | 1 | 0 | 1 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2 - Coh. EXP-1 (EGFR-WT NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2 - Coh. EXP-2 (Gastric or GEJ Adenocarcinoma) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.8 years STANDARD_DEVIATION 10.3 | 55.0 years STANDARD_DEVIATION 20.2 | 64.9 years STANDARD_DEVIATION 9.1 | 59.2 years STANDARD_DEVIATION 7.5 | 58.3 years STANDARD_DEVIATION 12.1 | 64.2 years STANDARD_DEVIATION 9.5 | 62.8 years STANDARD_DEVIATION 10.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 6 Participants | 45 Participants | 12 Participants | 10 Participants | 30 Participants | 107 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 1 Participants | 0 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 18 Participants | 0 Participants | 1 Participants | 18 Participants | 37 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 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 |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 6 Participants | 30 Participants | 12 Participants | 9 Participants | 12 Participants | 73 Participants |
| Region of Enrollment Poland | 0 participants | 0 participants | 16 participants | 0 participants | 3 participants | 4 participants | 23 participants |
| Region of Enrollment South Korea | 0 participants | 0 participants | 18 participants | 0 participants | 0 participants | 17 participants | 35 participants |
| Region of Enrollment Spain | 4 participants | 4 participants | 10 participants | 11 participants | 7 participants | 6 participants | 42 participants |
| Region of Enrollment United Kingdom | 0 participants | 1 participants | 4 participants | 1 participants | 0 participants | 1 participants | 7 participants |
| Region of Enrollment United States | 0 participants | 1 participants | 1 participants | 0 participants | 1 participants | 2 participants | 5 participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 13 Participants | 3 Participants | 7 Participants | 20 Participants | 51 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 36 Participants | 9 Participants | 4 Participants | 10 Participants | 61 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 |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 5 / 6 | 21 / 49 | 9 / 12 | 9 / 11 | 9 / 30 |
| other Total, other adverse events | 4 / 4 | 6 / 6 | 48 / 49 | 11 / 12 | 11 / 11 | 29 / 30 |
| serious Total, serious adverse events | 2 / 4 | 3 / 6 | 30 / 49 | 6 / 12 | 7 / 11 | 15 / 30 |
Outcome results
Primary
Phase 1: Incidence of 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 Technology Criteria for Adverse Events (CTCAE) v5.0
Time frame: During cycle 1 (each cycle has 28 days)
Population: Safety Analysis Set (SAS): All patients who received at least any amount of AFM24 or atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 | 0 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 1: Incidence of Dose Limiting Toxicities (DLTs) During Cycle 1 | 1 Participants |
Primary
Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR])
Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later.
Time frame: Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.
Population: Full Analysis Set (FAS): All patients who completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 8 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 1 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 1 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 4 Participants |
Secondary
Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24
Measurement of ADAs before and during treatment with AFM24 in combination with atezolizumab Patients with at least one ADA-positive result at baseline or post-baseline counted as developing anti-drug antibodies (ADAs) against AFM24
Time frame: Ph 1 within 2h prior to: each drug intake (Cycle 1), 1st + 3rd drug intake (Cycle 2 onwards) and at EOT, up to 27 weeks. Ph 2a within 2h prior to: 1st drug intake (Cycle 1 and Cycle 3 onwards), 1st + 3rd drug intake (Cycle 2) and at EOT, up to 97 weeks.
Population: Safety Analysis Set (SAS): All patients who received at least any amount of AFM24 or atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 1 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 2 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 12 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 2 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 3 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Frequency of Patients Developing Anti-drug Antibodies (ADAs) Against AFM24 | 7 Participants |
Secondary
Incidence of Patients With SAEs
Number of patients with treatment-emergent serious adverse events (serious TEAEs)
Time frame: From first drug administration up to 56 days after the last dose of AFM24, until the start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approximately 35 (phase 1) and 105 weeks (phase 2a).
Population: Safety Analysis Set (SAS): All patients who received at least any amount of AFM24 or atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 2 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 3 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 30 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 6 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 7 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With SAEs | 15 Participants |
Secondary
Incidence of Patients With TEAEs
Number of patients with treatment-emergent adverse events (TEAEs) non-serious or serious
Time frame: From first drug administration up to 30 (non-serious TEAEs) or 56 (serious TEAEs) days after last dose AFM24, until start of a subsequent anticancer treatment, or data cut-off date, whichever is sooner. Up to approx. 35 (phase 1) and 105 weeks (phase 2a).
Population: Safety Analysis Set (SAS): All patients who received at least any amount of AFM24 or atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 4 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 6 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 49 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 11 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 11 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Incidence of Patients With TEAEs | 30 Participants |
Secondary
Pharmacokinetics (PK) of AFM24
Time to Cmax (Tmax) on Cycle 1 Day 22
Time frame: During cycle 1 (each cycle has 28 days)
Population: All subjects who received at least one adequately documented dose of study drug and had sufficient PK measurements at Cycle 1 Day 22 analysed in central lab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 3.15 h | Standard Deviation 0.03 |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 3.15 h | Standard Deviation 0.13 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 9.78 h | Standard Deviation 17.9 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 27.9 h | Standard Deviation 24.5 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 8.63 h | Standard Deviation 15.8 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 10.6 h | Standard Deviation 17.4 |
Secondary
Pharmacokinetics (PK) of AFM24
Maximum plasma concentration (Cmax) on Cycle 1 Day 22
Time frame: During cycle 1 (each cycle has 28 days)
Population: All subjects who received at least one adequately documented dose of study drug and had sufficient PK measurements at Cycle 1 Day 22 analysed in central lab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 73700 ng/mL | Standard Deviation 25400 |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 269000 ng/mL | Standard Deviation 61400 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 207000 ng/mL | Standard Deviation 78100 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 207000 ng/mL | Standard Deviation 73400 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 175000 ng/mL | Standard Deviation 77200 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 250000 ng/mL | Standard Deviation 106000 |
Secondary
Pharmacokinetics (PK) of AFM24
Minimum plasma concentration (Cmin) Corresponding to Ctrough levels at the end of the dosing interval at Cycle 1 Day 22
Time frame: During cycle 1 (each cycle has 28 days)
Population: All subjects who received at least one adequately documented dose of study drug and had sufficient PK measurements at Cycle 1 Day 22 analysed in central lab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 16700 ng/mL | Standard Deviation 12500 |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 105000 ng/mL | Standard Deviation 37200 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 56300 ng/mL | Standard Deviation 48500 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 73700 ng/mL | Standard Deviation 40900 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 71900 ng/mL | Standard Deviation 62500 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 93700 ng/mL | Standard Deviation 51600 |
Secondary
Pharmacokinetics (PK) of AFM24
Area under the concentration-time curve over the dose interval (AUCtau) on Cycle 1 Day 22
Time frame: During cycle 1 (each cycle has 28 days)
Population: All subjects who received at least one adequately documented dose of study drug and had sufficient PK measurements at Cycle 1 Day 22 analysed in central lab.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 5760 hours*microgram /milliLiter | Standard Deviation 919 |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 27900 hours*microgram /milliLiter | Standard Deviation 9780 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 19800 hours*microgram /milliLiter | Standard Deviation 9660 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 21500 hours*microgram /milliLiter | Standard Deviation 8620 |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 20500 hours*microgram /milliLiter | Standard Deviation 11400 |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Pharmacokinetics (PK) of AFM24 | 28600 hours*microgram /milliLiter | Standard Deviation 11900 |
Secondary
Phase 1: Overall Response Rate (Complete Response [CR] or Partial Response [PR])
Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Overall Response Rate (CR or PR). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later.
Time frame: Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 27 weeks.
Population: Full Analysis Set (FAS): All patients who completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 1: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 1 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 1: Overall Response Rate (Complete Response [CR] or Partial Response [PR]) | 0 Participants |
Secondary
Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks)
Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Clinical benefit rate (CR or PR or SD ≥24 weeks). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1. Best overall response SD counts for Clinical benefit rate if SD ongoing for at least 24 weeks.
Time frame: Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.
Population: Full Analysis Set (FAS): All patients who completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks) | 11 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks) | 2 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks) | 1 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Clinical Benefit Rate (CR or PR [Any Duration] or Stable Disease Equal or > 24 Weeks) | 8 Participants |
Secondary
Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD])
Tumor assessment by RECIST v1.1 by investigator. Best overall response was used to define the Disease Control Rate (CR or PR or SD). Best overall response is CR or PR if a CR or PR assessed at least 42 days after Cycle 1 Day 1 was confirmed by subsequent tumor assessment at least 4 weeks later. Best overall response is SD if SD or unconfirmed CR or unconfirmed PR at least 42 days after C1D1.
Time frame: Tumor assessments were conducted during last week of cycle 2, 4, 6, 8, 10, 12 and every 3 cycles thereafter (each cycle has 28 days), up to approximately 97 weeks.
Population: Full Analysis Set (FAS): All patients who completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD]) | 27 Participants |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD]) | 5 Participants |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD]) | 2 Participants |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Disease Control Rate (DCR) (Complete Response [CR] or Partial Response [PR] or Stable Disease [SD]) | 14 Participants |
Secondary
Phase 2a: Duration of Response
Duration of Response (DOR) was defined as (date of first progression or death - date of first response (unconfirmed))/30.4375. Patients without response were excluded from the analysis. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator.
Time frame: From the date of first response (unconfirmed) until progression disease assessed by investigator or death.
Population: All patients from Full Analysis Set (FAS) (=completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab) who had a response by RECIST v1.1 by investigator assessment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 2a: Duration of Response | 9.20 Months |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Duration of Response | NA Months |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Duration of Response | 3.71 Months |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Duration of Response | 11.07 Months |
Secondary
Phase 2a: Progression-free Survival
Progression-Free Survival (PFS) was defined as (date of first progression - date of first study drug injection)/30.4375. Patients without progression or death were censored. Tumor assessment by RECIST v1.1 by investigator.
Time frame: From the first treatment received until the first progression disease assessed by investigator or death.
Population: Full Analysis Set (FAS): All patients who completed the Safety Lead-in phase and received any amount of any component of the combination treatments AFM24 and atezolizumab
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Phase 1 - Cohort 1 - AFM24 160 mg + Atezolizumab 840 mg | Phase 2a: Progression-free Survival | 3.75 Months |
| Phase 1 - Cohort 2 - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Progression-free Survival | 1.94 Months |
| Phase 2 - Coh. EXP-3 (Hepatocellular,Hepatobiliary,Pancreatic) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Progression-free Survival | 1.91 Months |
| Phase 2 - Coh. EXP-4 (EGFR Kinase Domain Mutation NSCLC) - AFM24 480 mg + Atezolizumab 840 mg | Phase 2a: Progression-free Survival | 3.71 Months |