A Phase 1/2a Study to Assess AFM24 in Advanced Solid Cancers
Research type
Research Study
Full title
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
IRAS ID
272676
Contact name
Juanita Lopez
Contact email
Sponsor organisation
Affimed GmbH
Eudract number
2019-003296-19
Duration of Study in the UK
3 years, 1 months, 2 days
Research summary
Research Summary -
AFM24 is a newly developed, potential anticancer drug, and will be administered to humans for the first time in this study.
AFM24 is an antibody designed artificially to bind to tumour cells and also to immune cells called “natural killer” cells and “macrophages”. Antibodies are molecules produced by the immune system to fight infections. The primary function of immune cells is to fight infections or kill tumour cells. AFM24 has the potential to create a connection between tumour cells and immune cells. After this connection is created the immune cells could be able to kill the cancer cells.
This study is split into two parts, a dose escalation phase (with approximately 35 patients) followed by a dose expansion phase (with 40 patients). The aim of the dose escalation phase is to find a safe dose by determine the Maximum Tolerated Dose and establish the recommended dose for the next part of the study, the dose expansion phase. The dose expansion part of the study is intended to collect preliminary evidence of anti-tumour activity and to further confirm the safety of the AFM24 in adult patients with solid cancers whose disease has progressed after treatment with previous anticancer therapies.
This is an open (the investigator and the patient will know what drug is given), uncontrolled (all participants will receive study drug), study and is planned to run in 1 hospital in the UK (The Royal Marsden Hospital), 3 additional hospitals in Europe and a further 2 hospitals in the US.
The study consists of a screening period of a maximum 14 days; a treatment period with AFM24 lasting until disease progression, an intolerable adverse event or withdrawal of the patient occurs; and a post-treatment period lasting until the end of the study.
This study is being sponsored by Affimed GmbH.Lay Summary of Results -
Layperson Synopsis of the AFM24-101 Clinical Study Report Results
Affimed GmbH, the sponsor of the AFM24-101 clinical trial, would like to thank the study participants for taking part in this research and their invaluable contribution toward the efforts to develop this potential new cancer treatment.
Study Title: A Phase 1/2a Open-Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of AFM24 in Patients with Advanced Solid CancersEU CT Number: 2024-511999-32-00
Overview: There were five countries (Germany, South Korea, Spain, United Kingdom, United States) that were part of this study with a total of 12 medical sites that enrolled patients. In the first part of the study (Phase 1 - dose escalation), in which the dose of the study drug is increased for groups of patients until the best dose to give patients is found, 35 patients were treated. The phase 1 part of the study had the first patient sign up to participate on 09 March 2020 and the last patient’s last visit to their medical site as part of the study was on 31 May 2023.
In the second part of the study, dose expansion (Phase 2a), in which additional patients are treated with the phase 1 study drug dose of 480mg, 50 patients were treated. For this part of the study the last patient’s last visit to their medical site as part of the study was on 24 June 2024.
Patients with particular types of solid tumour cancers were able to participate in the study. These were patients who had already gotten the usual treatment(s) for their type of cancer, but whose cancer had gotten worse. The goal of the study was to find out about the safety of this treatment, how well patients’ bodies could handle the treatment, and how well it might work against cancer. In the Phase 2a part of the study, the participants had to have one of three particular types of cancer in order to be in the trial. These cancers were a specific kind of Colorectal Cancer (bowel or colon), a specific kind of Renal Cell Carcinoma (kidney), and advanced or metastatic NSCLC (a specific kind of Non-Small Cell Lung Cancer).
After patients had the procedures, the risks, and other details about the study explained to them, they signed an Informed Consent form to agree to take part in the study. Next, each patient was checked and had tests to see if they met entry criteria, so they could take part in the study. For the patients who did start, the study medication was given as an infusion intravenously (as a liquid through a needle directly inserted into the patient’s vein). The patients were allowed to continue on the study as long as their doctor agreed it was a benefit for them, or until their disease got worse, their body could not handle the study medication any longer, their doctor thought it would be better for them to stop, they didn’t want to participate any longer, or other reasons for patients to stop, which were defined in the study protocol, occurred. After patients stopped treatment, their condition was followed to see how they did, including how long their cancer continued to respond to treatment without progressing, and how long they survived from when the study treatment started.After the phase 1 part of the study, before the phase 2 portion started, an Independent Data Monitoring Committee (IDMC) was formed - made up of clinical experts who were not directly involved in this clinical study. They reviewed all safety data that was gathered throughout the phase 2 part of the study on a regular basis. Based on their reviews, this group provided recommendations to the Sponsor with regard to how the study or study procedures were done.
When the phase 1 part of the study was done, the dose of study medication for the phase 2 part was determined. In the phase 2 there would be three cohorts or groups that would be treated.
• Cohort A could enrol up to 39 patients who had Colorectal Cancer (bowel or colon cancer); an early analysis of the study data was planned to be conducted after 11 patients were enrolled.
• Cohort B could enrol up to 41 patients with a specific kind of Renal Cell Carcinoma (kidney cancer); an early analysis of the study data was planned to be conducted after 15 patients were enrolled.
Note: The study was stopped earlier than planned for futility (a lack of sufficient benefit) based on the early analysis of study data that was done for Cohort A and C. The part of the study for kidney cancer was stopped early after 8 patients, because it was believed to be unlikely to have a real benefit for the patients.
• Expansion Cohort C was planned to enrol up to a total of 41 patients with advanced or metastatic NSCLC (a specific kind of Non-Small Cell Lung Cancer); the early analysis was planned to be conducted after 15 patients were enrolled.Efficacy (Treatment Benefit) Results:
Phase 2a
The main analysis of efficacy (treatment benefit to patients) was based on the OR (Overall Response). The OR is the percentage of people in the study who have a partial response or complete response to the treatment within a certain period of time. A partial response is a decrease in the size of a tumour or in the amount of cancer in the body, and a complete response is the disappearance of all signs of cancer in the body. In a clinical trial, measuring the OR is one way to see how well a new treatment works. The main analysis on how effective the treatment was, was based on Overall Response as measured by each Investigator using a solid tumour evaluation tool known as RECIST 1.1. Even though early analysis proved that AFM24 showed some activity in Cohort C, it was judged not to be enough, and the study was stopped early for futility (lack of sufficient effect). Based on the Investigator RECIST 1.1 assessment, no patient in any cohort showed Complete Response. Partial Response (some decrease in tumour size) was seen for 2 patients in Cohort C; no patients had Partial Response in Cohort A or Cohort B. Therefore, Overall Response Rate (Complete Response + Partial Response) was 0 for both Cohort A and Cohort B; Overall Response Rate for the Phase 2 study was 2 patients.The secondary analysis on the effectiveness of the treatment was looking at Duration Of Response (the length of time a patient’s cancer responds to the treatment before progression occurs). This was also measured by Investigators using the RECIST 1.1 tool. A Duration Of Response (DOR) was reported for 2 patients in Cohort C; 1 patient had a DOR where progression appeared at 3.6 months and 1 patient’s response was not listed since there was no progression or death by the time the study ended. There were no patients who responded in Cohort A or Cohort B.
Time to response (TTR), (the amount of time from the start of study drug until a decrease in tumour size could be measured) was assessed by Investigators using the RECIST 1.1 tool. In the study this was reported for 2 patients (8.7%) in Cohort C. For the remaining patients in all 3 cohorts, there was either no response or no measurement of their tumour(s) to compare to the first measurement when they started. For the second measurement of how well the treatment worked the Investigators used the RECIST 1.1 tool to determine PFS. PFS (Progression-Free Survival), is the length of time during and after the treatment of a disease, that a patient lives with that disease but it does not get worse. PFS events were reported for 17 patients (89.5%) in Cohort A, 7 patients (87.5%) in Cohort B, and 18 patients (78.3%) in Cohort C. The overall average estimate of PFS was 1.64 months. For the secondary measurement of how well the treatment worked, OS (Overall Survival) was measured. Overall Survival is the percentage of people with a specific type and stage of cancer who have not died from any cause during a certain period of time after diagnosis. For Overall Survival, deaths were reported for 14 patients (73.7%) in Cohort A, 6 patients (75.0%) in Cohort B, and 7 patients (30.4%) in Cohort C. The overall average OS was 10.68 months.
Conclusions:
• In the Phase 1 dose escalation part of the study, no Maximum Tolerated Dose (MTD) was reached. The Maximum Tolerated Dose is defined as the highest dose of a drug that does not cause unacceptable side effects or cause obvious harm in a specific period of time. Based on other data, the Recommended Phase 2 Dose was determined at 480 mg.
• In the Phase 2a dose expansion part of the study, even though AFM24 did demonstrate some activity in Cohort C, the Overall Response was found to be insufficient, and the study was stopped early for futility (lack of sufficient effect), after the early analysis was completed.
• Safety findings of AFM24 alone were in line with what is known about how the drug works, the underlying disease, and the expected types of risks that might be expected of AFM24. Overall, the treatment with AFM24 was handled by patients well, with manageable patient risks and Adverse Events. An Adverse Event or AE (refers to any unfavourable or unintended sign, symptom, or disease associated with the use of a medical product, whether or not it is considered related to the product itself and can range from mild to severe.REC name
London - Hampstead Research Ethics Committee
REC reference
20/LO/0222
Date of REC Opinion
11 Mar 2020
REC opinion
Further Information Favourable Opinion