Advanced solid malignancies in patients whose disease has progressed after treatment with previous anticancer therapies. MedDRA version: 21.0 Level: LLT Classification code 10048683 Term: Advanced cancer System Organ Class: 100000004864
Conditions
Sponsors
Affimed GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients with histologically or cytologically confirmed advanced or metastatic solid malignancies that are known to express EGFR, or in which EGFR is thought to be a relevant therapeutic target, including but not limited to: colorectal, lung, gastric, esophageal, pancreatic, head and neck, breast, ovarian, cervical, urothelial, and renal cancers, and glioblastoma multiforme 2) Patients must have been previously treated with one or more 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 3) Voluntary provision and understanding of signed and dated, written informed consent prior to any mandatory study-specific procedures, sampling, or analysis 4) Male or female aged =18 years on the day of signing informed consent 5) Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1 =7 days before first AFM24 infusion 6) Adequate organ function within 14 days before first AFM24 infusion, as defined as in the protocol. Patients must also be assessed as meeting these criteria on or within 7 days of the first AFM24 infusion to remain eligible 7) Serum potassium, calcium, magnesium and phosphorus within normal limits. If values are low on the initial screening assessment, supplements may be given and values repeated to confirm within normal limits 8) Patients must have at least one tumor site that is accessible to biopsy and that is considered by the Investigator to be low risk and of sufficient size to undergo a core biopsy procedure on at least 2 separate occasions 9) Phase 2a only: Patients must have measurable disease per RECIST v1.1 (i.e., at least 1 measurable lesion =10 mm by CT scan or MRI or =20 mm by chest X ray, malignant lymph nodes are considered measurable if short axis is =15 mm assessed by CT scan), with the last imaging performed within 28 days before Cycle (C) 1 Day (D) 1 (C1D1) 10) Patients in Phase 2a must have a disease history specific to their disease as listed below: • Colorectal Cancer: Patients with metastatic colorectal carcinoma (mCRC) whose disease has progressed following prior treatment with oxaliplatin, irinotecan and a fluoropyrimidine for metastatic disease. Patients must have documentation of RAS mutational status. If RAS is wildtype, prior therapy must have included an approved anti-EGFR monoclonal antibody, i.e., either cetuximab or panitumumab, as a component. For patients with microsatellite instability-high or mismatch repair deficient mCRC prior lines of therapy must have included a checkpoint inhibitor if approved and available • NSCLC without a targetable EGFR mutation: Patients with advanced or metastatic NSCLC whose disease has progressed after having received =2 prior lines of therapy for advanced disease, which must have included platinum-based therapy and an anti-PD-1/PD-L1 antibody. Patients must have documentation of NSCLC without a targetable EGFR mutation as assessed by genomic sequencing of tumor or circulating free tumor DNA. Patients with a targetable mutation other than EGFR must have received an approved targeted treatment if available. Patients with anaplastic lymphoma kinase (ALK)-positive tumor must have received an approved ALK inhibitor such as crizotinib, ceritinib, alectinib or lorlatinib. Patients with ROS proto-oncogene 1 receptor t
Exclusion criteria
Exclusion criteria: 1) 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. 2) Treatment with systemic anticancer therapy within 4 weeks (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. 3) Radiation therapy within 2 weeks before first dose of study drug or unresolved (National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v5.0 >Grade 1) toxicity from previous radiotherapy (e.g., radiation dermatitis). 4) Major surgery within 4 weeks before first dose of study drug. 5) Patients with toxicities (as a result of prior anticancer therapy) which have not recovered to baseline or CTCAE v5.0 = Grade 2, except for AEs not considered a likely safety risk (e.g., alopecia, specific laboratory abnormalities). 6) 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, ductal carcinoma in situ (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. 7) One or more of the following cardiac criteria: Unstable angina; Myocardial infarction within 6 months prior to screening; New York Heart Association Class II to IV heart failure; Corrected QT interval (QTc) >470 msec obtained as the mean from 3 consecutive resting electrocardiograms (ECGs) using the Fridericia’s formula; Clinically important abnormalities in rhythm, conduction, or morphology of resting ECG (e.g., complete left bundle branch block or third-degree heart block); Congenital long QT syndrome; Uncontrolled hypertension (=140/90 mmHg based on accurate measurement and average of =2 readings which are =5 minutes apart on =2 occasions). 8) Stroke or transient ischemic attack within 6 months prior to screening. 9) History of leptomeningeal disease or spinal cord compression. 10) Known brain metastases unless asymptomatic and not requiring steroids for at least 4 weeks prior to start of study treatment. 11) Patients with primary brain tumor who require high dose steroids (defined as=30 mg prednisolone or equivalent per day) or who received high dose steroids within 4 weeks prior to first dose of study treatment. 12) Diagnosis of immunodeficiency or active infection including known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). 13) Active autoimmune disease that requires systemic treatment with steroids or other immunosuppressive agents, or patients who have received such agents within 1 months prior to first dose of study treatment. Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment. 14) Patients who require systemic steroid treatment or any other immunosuppressive therapy, or patients who received such therapy within 4 weeks prior to the first dose of study treatment, with the exception of steroid allowance for primary brain tumor as outlined in exclusion criterion 11, or for physi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: PHASE 1: Determine the maximum tolerated dose (MTD), select a recommended phase 2 dose (RP2D), and investigate the safety and tolerability of AFM24 in patients with advanced solid malignancies. PHASE 2a: Assess the preliminary anti-tumor efficacy of AFM24, using tumor response criteria as defined by local RECIST v1.1;Secondary Objective: PHASE 1: Characterize the pharmacokinetics (PK) of AFM24 administered intravenously (i.v.); Characterize the immunogenicity of AFM24; and assess the preliminary anti-tumor efficacy of AFM24, using tumor response criteria as defined by: Local Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, Local immune-related RECIST (iRECIST), Central RECIST v1.1, Central iRECIST PHASE 2a: Characterize the safety and tolerability of AFM24, including both acute and chronic toxicities; Characterize the PK of AFM24 administered i.v.; Characterize the immunogenicity of AFM24; and Assess the preliminary anti-tumor efficacy of AFM24, using tumor response criteria as defined by: Local iRECIST; Central RECIST v1.1; and Central iRECIST ;Primary end point(s): PHASE 1: The incidence of dose limiting toxicities (DLT) during DLT observation period. PHASE 2a: Overall response rate (CR+PR) assessed by local RECIST v1.1. ;Timepoint(s) of evaluation of this end point: PHASE 1: For cohorts 1&2, at least 2 patients, and for cohorts 3+, at least 3 patients, need to be evaluable for the dose-determining set. Patients must receive =80% of their assigned AFM24 dose in Cycle 1 and complete the 28-day DLT observation period or have had a DLT within the first cycle of treatment to be considered evaluable for DLT. Safety will be assessed by periodic vital signs, physical examinations, ECOG PS, 12-lead ECGs, clinical laboratory assessments, and monitoring of adverse events (AEs). PHASE 2a: Tumor assessment with CT and/or MRI will occur at Screening as well as during the last week of Cycles 2, 4, 6, 8, and every 3 cycles thereafter. Parti | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): PHASE 1: Serum PK parameters: area under the concentrationtime curve (AUC), Cmax, minimum plasma concentration (Cmin), clearance (CL), volume of distribution (Vd), volume of distribution at steady state (Vss), terminal t½ Measurement of anti-drug antibodies (ADA) before and throughout treatment with AFM24 Overall response rate (complete response [CR] + partial response [PR]), duration of response (DOR), and disease control rate (CR + PR + stable disease [SD]) assessed by Local RECIST v1.1; Local iRECIST; Central RECIST v1.1; and Central iRECIST. Progression-free survival (PFS), and overall survival (OS) measured by local and central assessments. PHASE 2a: AEs, SAEs, and changes between baseline and postbaseline laboratory parameters including ECGs, vital signs, and physical exams PK parameters: AUC, Cmax, Cmin, CL, Vd, Vss, terminal t½ Measurement of ADA before and throughout treatment with AFM24 OR (CR + PR) assessed by Local iRECIST; Central RECIST v1.1; and Central iRECIST. DOR, and disease control rate (CR + PR + SD) assessed by Local RECIST v1.1; Local iRECIST; Central RECIST v1.1; and Central iRECIST. PFS, OS measured by local and central assessments;Timepoint(s) of evaluation of this end point: Phase 1 & 2a: Safety will be assessed by periodic vital signs, physical examinations, ECOG PS, 12-lead ECGs, clinical laboratory assessments, and monitoring of adverse events (AEs). Blood samples for PK assessments will be drawn during Cycle 1 on Days 1, 3, 7, 8, 15, 22, 24, and 28 as well as during Cycle 2 on Days 1, 8, 15, and 22, and during subsequent cycles on Day 1. PK Blood samples will also be drawn at the End of Treatment visit.. ADA will be measured on Days 1, 8, 15, and 22 in every cycle, and at the End of Treatment visit. Disease response will be assessed by the Investigator, and imaging results will be sent for independent central review. After the end of treatment patients will be followed for safety, DOR, PFS and OS until | — |
Countries
Germany, Spain, United Kingdom, United States
Contacts
Public ContactClinical Trial Manager
Affimed GmbH
Outcome results
None listed