Phase 1b multi-indication study of anetumab ravtansine
Research type
Research Study
Full title
Phase 1b multi-indication study of anetumab ravtansine (BAY 94-9343) in patients with mesothelin expressing advanced or recurrent malignancies
IRAS ID
223951
Contact name
Matthew Krebs
Contact email
Sponsor organisation
Bayer AG
Eudract number
2016-004002-33
Clinicaltrials.gov Identifier
Duration of Study in the UK
2 years, 4 months, 20 days
Research summary
Summary of Research
The key purpose of the main part of the study is to assess efficacy and safety of anetumab ravtansine as monotherapy or combination therapy for mesothelin expressing advanced solid tumours.\nThe main purpose of the safety lead-in (dose-finding) part of the study is to determine the safety and tolerability of anetumab ravtansine in combination with cisplatin and in combination with gemcitabine, and to determine the Maximum Tolerated Dose (MTD) of anetumab ravtansine in combination with cisplatin for mesothelin expressing advanced cholangiocarcinoma and in combination with gemcitabin for mesothelin expressing advanced adenocarcinoma of the pancreas.\nPatients will receive anetumab ravtansine every three weeks in monotherapy for most indications. In cholangiocarinoma and adenocarinoma of the pancreas, 3-weekly anetumab ravtansine is administered in combination with cisplatin or gemcitabine respectively (both administered in a 2 week on / 1 week off schedule).\nTreatment will continue until disease progression or until another criterion for withdrawal is met. Efficacy will be measured by evaluating the tumour’s objective response rate. Radiological tumour assessments will be performed at defined time points until the patient’s disease progresses. \nBlood samples will be collected for safety, pharmacokinetic and biomarker analysis. Archival or fresh biopsy tissue may also be collected for review and biomarkers. \n
Summary of Results
This is a summary of the main results from this trial. The individual results of each participant might be different and are not in this summary. The results from several trials are needed to better understand which treatments work best and are safest. Other trials may provide new information or different results.
What was the highest dose of anetumab ravtansine the participants could safely receive with chemotherapy?
To answer this question, the doctors counted the number of dose-limiting toxicities the participants in Groups 5 and 6 had during this trial. A dose-limiting toxicity is also known as a “DLT”. A DLT is a medical problem that is severe enough to stop the doctor from increasing the dose of trial treatment in the next group of participants. Learning the number of DLTs that participants have helps researchers learn about the maximum tolerated dose, also called the “MTD”. The MTD is the highest dose that participants can receive without having DLTs.
In Group 5 and Group 6, the first dose of anetumab ravtansine was 5.5 mg/kg once every 3 weeks. Then, the researchers would either increase a participant’s dose to 6.5 mg/kg or decrease the dose to 4.5 mg/kg depending on how many DLTs they had. The researchers could only include the information from the participants in Groups 5 and 6. So, the below results only include 36 of the 173 participants. In this trial, the researchers found that none of these 36 participants had DLTs. So, the researchers determined that the MTD of anetumab ravtansine was 6.5 mg/kg once every 3 weeks. This was the highest dose of anetumab ravtansine that the researchers in this trial wanted to study.
How did anetumab ravtansine affect the participants’ cancer?
To answer this question, the doctors took images of the participants’ tumors using either a CT or MRI scan. They did this before the participants received treatment, and at different times throughout the trial. To measure the growth of the participants’ tumors during the trial, the doctors used a set of rules called the modified Response Evaluation Criteria In Solid Tumors, also called “mRECIST”. The researchers calculated the percentage of participants who had their tumors disappear or shrink by at least 30.0%.
Because the trial ended early, 106 participants left this trial before receiving all of their trial treatments. So, the results below include 67 participants from Groups 1, 2, and 6. Overall, the researchers found that the percentage of participants who had their tumors disappear or shrink by at least 30.0% was:
• 19.0% of participants in Group 1. This was 4 out of 21 participants.
• 7.4% of participants in Group 2. This was 2 out of 27 participants
• 31.6% of participants in Group 6. This was 6 out of 19 participants.
The researchers also studied the percentage of participants who had their tumors disappear, shrink by at least 30.0%, or stay the same for at least 180 days. The researchers planned to study this in 83 participants in Groups 2 and 6. This was because the researchers wanted to learn more about how anetumab ravtansine affects tumors in people with gastric adenocarcinoma and pancreatic adenocarcinoma. But, 37 of these participants left this trial before receiving all of their trial treatments. So, the results below only include 46 participants from Groups 2 and 6.
Overall, the researchers found that the percentage of participants who had their tumors disappear, shrink by at least 30.0%, or stay the same for at least 180 days was:
• 3.7% of participants in Group 2. This was 1 out of 27 participants.
• 42.1% of participants in Group 6. This was 8 out of 19 participants.
This trial helped researchers learn more about the safety of different doses of anetumab ravtansine, and how anetumab ravtansine affected people with advanced or recurrent cancer. The results from several trials are needed to better understand which treatments work best and are safest. This summary only shows the main results from this one trial. Other trials may provide new information or different results.
Further clinical trials with anetumab ravtansine are not planned.REC name
North West - Greater Manchester South Research Ethics Committee
REC reference
17/NW/0292
Date of REC Opinion
15 Jun 2017
REC opinion
Further Information Favourable Opinion