In short
Clinical trials are investigating 2-[4-[4-(AMINOMETHYL)-1-OXO-2H-PHTHALAZIN-6-YL]-2-METHYLPYRAZOL-3-YL]-4-CHLORO-6-CYCLOPROPYLOXY-3-FLUOROBENZONITRILE in people with advanced cancers that have homozygous MTAP deletion. These studies look at whether it helps improve outcomes such as tumor response, time without disease worsening, and overall survival in pancreatic cancer and non-small cell lung cancer.
Key points
- Clinical trials are studying 2-[4-[4-(AMINOMETHYL)-1-OXO-2H-PHTHALAZIN-6-YL]-2-METHYLPYRAZOL-3-YL]-4-CHLORO-6-CYCLOPROPYLOXY-3-FLUOROBENZONITRILE in advanced cancers with homozygous MTAP deletion. The main conditions are untreated metastatic pancreatic ductal adenocarcinoma and advanced or metastatic non-small cell lung cancer. The trial phases shown in the source data are Phase 2 and Phase 3 within studies labeled Phase 4. The studies include both people who have not yet had treatment for their metastatic disease and people who have already been treated. Main endpoints include objective response, progression-free survival, time to disease worsening on scans, and overall survival. The trials compare 2-[4-[4-(AMINOMETHYL)-1-OXO-2H-PHTHALAZIN-6-YL]-2-METHYLPYRAZOL-3-YL]-4-CHLORO-6-CYCLOPROPYLOXY-3-FLUOROBENZONITRILE alone or with other cancer medicines against placebo-based treatment plans.
Trial overview
The source data describe three interventional studies of 2-[4-[4-(AMINOMETHYL)-1-OXO-2H-PHTHALAZIN-6-YL]-2-METHYLPYRAZOL-3-YL]-4-CHLORO-6-CYCLOPROPYLOXY-3-FLUOROBENZONITRILE, also listed in the trial titles as BMS-986504 and Navlimetostat. All three studies are marked Authorised and focus on cancers with homozygous MTAP deletion, which means both copies of the MTAP gene are missing.
Two studies are in metastatic non-small cell lung cancer, and one study is in untreated metastatic pancreatic ductal adenocarcinoma. The studies compare the research treatment with placebo in some settings, and with standard cancer treatment combinations in others.
Study in metastatic pancreatic cancer
One trial is titled as a study of BMS-986504 in combination with nab-p/gem versus placebo in combination with nab-p/gem in untreated metastatic PDAC with homozygous MTAP deletion. PDAC means pancreatic ductal adenocarcinoma, which is a common type of pancreatic cancer.
This study is designed to see whether the combination can prolong the time to disease worsening on scans and prolong survival. The primary outcome is listed as time to disease worsening on scans and time to death, which are patient-important measures of whether the disease stays controlled longer.
The trial is in Phase 4 in the source record and has an enrollment of 470 participants. The study includes people with untreated metastatic disease, meaning the cancer has spread and has not yet been treated in this study setting.
Studies in non-small cell lung cancer
One lung cancer study is titled as a study of Navlimetostat (BMS986504) in participants with pre-treated advanced or metastatic non-small cell lung cancer with homozygous MTAP deletion. This means the study includes people whose lung cancer is already advanced and who have had prior treatment.
This study evaluates objective response, which means how many participants have their tumors shrink or disappear based on scan rules called RECIST v1.1. The study is listed as Phase 2 and has an enrollment of 130 participants.
The other lung cancer study is a first-line metastatic non-small cell lung cancer trial that tests BMS-986504 with pembrolizumab and chemotherapy versus placebo with pembrolizumab and chemotherapy in people with homozygous MTAP deletion. “First-line” means the first treatment given for that metastatic cancer setting.
This study has two main goals in Phase 3: compare progression-free survival and compare overall survival between the treatment groups. The source record lists an enrollment of 580 participants and marks the study as Phase 4.
Phases and study design
The trial data show a mix of phase labels and phase objectives. One study is a Phase 2 trial focused on tumor response, while the other two are labeled Phase 4 in the source records but include Phase 3 outcome goals such as progression-free survival and overall survival.
All three studies are interventional, which means the researchers are assigning a treatment plan and then measuring the results. The treatment plans include the study drug alone or with other cancer medicines, and some groups receive a matching placebo instead of the study drug.
Main endpoints being measured
The main outcome in the pancreatic cancer study is time to disease worsening on scans and time to death. These outcomes help show whether treatment delays cancer growth and may help people live longer.
The Phase 2 lung cancer study measures objective response using RECIST v1.1. This is a standard way to judge whether tumors have shrunk in a reliable and fair way.
The first-line lung cancer study measures progression-free survival in both Phase 2 and Phase 3 parts, and overall survival in Phase 3. Progression-free survival means the time before the cancer gets worse, and overall survival means the time people stay alive after starting study treatment.
Who the trials are for
These studies are aimed at people with homozygous MTAP deletion and advanced cancer. The pancreatic study is for people with untreated metastatic pancreatic ductal adenocarcinoma, while the lung cancer studies are for people with advanced or metastatic non-small cell lung cancer, including people who are pre-treated or starting first-line therapy.
The source data do not provide full inclusion or exclusion rules, so the most important known eligibility feature is the cancer type plus the MTAP deletion status.
Key points from the trial data
- Three authorised studies are listed for 2-[4-[4-(AMINOMETHYL)-1-OXO-2H-PHTHALAZIN-6-YL]-2-METHYLPYRAZOL-3-YL]-4-CHLORO-6-CYCLOPROPYLOXY-3-FLUOROBENZONITRILE.
- One study is in untreated metastatic pancreatic ductal adenocarcinoma, and two are in metastatic non-small cell lung cancer.
- The studies measure response, progression-free survival, time to disease worsening, and overall survival.
- Enrollment ranges from 130 to 580 participants across the trials.
- The trial designs include placebo-controlled comparisons and combination treatment plans.