A Phase 1/2a Study to Assess AFM24 in Advanced Solid Cancers
- Conditions
- Advanced solid malignancies in patients whose disease has progressed after treatment with previous anticancer therapies.MedDRA version: 21.0Level: LLTClassification code 10048683Term: Advanced cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003296-19-DE
- Lead Sponsor
- Affimed GmbH
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 150
1) For the dose escalation phase (Phase 1): histologically or cytologically confirmed advanced or metastatic solid malignancies that are known to
express EGFR. For the dose expansion phase (Phase 2a): histologically or cytologically confirmed advanced or metastatic EGFR malignancies. EGFR expression is defined as positive staining for EGFR in =1% of tumor cells, determined by a validated immunohistochemistry assay. Archived paraffin embedded tumor tissue is acceptable for EGFR determination – otherwise a fresh tumor biopsy must be performed. Local laboratory EGFR assessment is acceptable.
2) For dose escalation phase (Phase 1): Subjects must have been previously treated with 1 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 subject or the remaining SOC therapies are deemed not appropriate for the subject by the Investigator.
3) Subjects must have documented radiological progression during or after their latest therapy for all phases.
4) Voluntary provision and understanding of signed and dated, written informed consent prior to any mandatory study-specific procedures, sampling, or analysis
5) Male or female aged >=18 years on the day of signing informed consent (or of an acceptable age according to local regulations, whichever is older).
6) Eastern Cooperative Oncology Group (ECOG) Performance Score (PS) 0 or 1
7) Adequate organ function assessed within 14 and within 7 days before first AFM24 infusion, as defined as in the protocol. Note: transfusions and hematopoietic growth factors to help meet eligibility are not allowed
8) Serum potassium, calcium, magnesium and phosphate within normal limits or not worse than CTCAE v5.0 Grade 1 and asymptomatic. If values
are low on the initial screening assessment, supplements may be given, if clinically appropriate, and values repeated to confirm within CTCAE
v5.0 Grade 1 limits.
9) For dose escalation phase (Phase 1): Subjects must have (mandatory) at least 1 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.
10) For dose expansion phase (Phase 2a) only: Subjects must have measurable disease per RECIST v1.1 (i.e., at least 1 measurable lesion >=10 mm by computed tomography [CT] scan or magnetic resonance imaging (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 1 Day 1 (C1D1).
11) Subjects in dose expansion phase (Phase 2a) must have histologically confirmed advanced or metastatic EGFR-positive malignancy for each expansion cohort, as listed below:
• Cohort A: Subjects with RAS-wildtype, microsatellite stable CRC whose disease has progressed after having received =2 prior lines of therapy, which must have included oxaliplatin, irinotecan, fluoropyrimidine. If available, prior therapy must also have included an anti-VEGF or, anti-
VEGFR and it's receptor (anti-VEGFR) therapy (eg, bevacizumab, aflibercept, or ramucirumab), and an anti-EGFR therapy (eg, cetuximab or panitumumab).
• Cohort B: Subjects with ccRCC whose disease has progressed after having received =1 prior line(s) of therapy, which must have included a
TKI (e.g., sunitinib, pazopanib), and a checkpoint inhibitor (e
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 drug.
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] CTCAE v5.0 >Grade 1) toxicity from previous radiotherapy (e.g., radiation dermatitis).
4)Major surgical procedure, open biopsy, or significant traumatic injury within 4 weeks before first dose of study drug or anticipation of need of a major surgical procedure during the course of study. Note: Procedures that are considered to be minimally invasive (eg, peripherally inserted central catheters lines and/or port placements) will be exception.
5)Subjects 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 invasive malignancy, unless previously treated with curative intent and the subject has been disease free for 3 years or longer. Examples for acceptable previous malignancies include: completely removed in situ cervical intra-epithelial neoplasia, nonmelanoma skin cancer, ductal carcinoma in situ, and early-stage prostate cancer that has been adequately treated.
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 >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 (>= 150/100 mmHg based on accurate measurement and average of >=2 readings which are >=5 minutes apart on >=2 occasions) despite maximum antihypertensive therapy.
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 drug.
11)Subjects 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 drug.
12)Diagnosis of immunodeficiency or active infection including known hepatitis B, hepatitis C, or human immunodeficiency virus (HIV). A negative confirmatory test within 3 months of treatment start does not have to be repeated during the screening period.
13)Active autoimmune disease that requires systemic treatment with steroids or other immunosuppressive agents, or subjects who have received such agents within 4 weeks prior to first dose of study drug.
Exceptions:
• Topical (=20% of the skin surface area), ocular, intra-articul
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method