How to use this page
- These trials choose patients by a molecular alteration — MDM2 or CDK4/CDK6 amplification, p53 status, Rb status — rather than only by the name of the diagnosis.
- That is what makes them relevant if your tumour is too rare to have trials of its own.
- Status shown is what the public registry said on 29 September 2026. Trials open, close and amend their criteria constantly — always open the registry link and check before acting.1
- Nobody can tell from a web page whether you are eligible. Only the trial team can, and they will need your pathology and molecular reports.
- If you are not sure how to approach a trial site, write to us. A patient answers.
Trials that enrol on the amplification, whatever the tumour is
These are the studies where the diagnosis on your report matters less than the alteration in it.
| Trial | Selects for | Drug | Phase · where | Status |
|---|---|---|---|---|
| MegaMOST NCT04116541 Centre Léon Bérard |
HDM201–ribociclib cohort: CDK4 and/or CDK6 amplification, or CDKN2A homozygous deletion, or CCND1/CCND3 amplification — with Rb intact and p53 wild-type. Any advanced solid tumour. | Siremadlin (HDM201, MDM2 inhibitor) + ribociclib (CDK4/6 inhibitor) | Phase II · ~10 centres across France (Lyon, Villejuif, Bordeaux, Marseille, Toulouse, Nice, Caen, Strasbourg) | Recruiting |
| Abemaciclib in cyclin-pathway altered tumours NCT03310879 Dana-Farber Cancer Institute |
Solid tumours with alterations in D-type cyclin genes or amplification of CDK4 or CDK6. Histology-agnostic. | Abemaciclib | Phase II · Boston, USA | Recruiting |
| SA53-OS NCT06578624 Lamassu Bio |
Locally advanced or metastatic p53 wild-type solid tumours — the setting in which releasing p53 from MDM2 can work. | SA53-OS (MDM2 inhibitor) | Phase I/IIa · 3 centres, USA | Recruiting |
| APG-115 + toripalimab NCT04785196 Ascentage Pharma |
Advanced liposarcoma or other advanced solid tumours — combines MDM2 inhibition with PD-1 blockade. | Alrizomadlin (APG-115) + toripalimab | Phase Ib/II · 3 centres | Recruiting |
| Abemaciclib in CDK-pathway altered sarcoma NCT04040205 Medical College of Wisconsin |
Advanced bone and soft-tissue sarcoma identified as having a CDK pathway alteration — any sarcoma histology. | Abemaciclib | Phase II · 4 centres, USA | Recruiting |
Why MegaMOST is worth a closer look from Europe. It is the only trial on this list that combines an MDM2 inhibitor with a CDK4/6 inhibitor, selects explicitly on CDK4/CDK6 amplification with intact Rb and wild-type p53, accepts any advanced solid tumour, and runs at a network of French sarcoma centres — including Centre Léon Bérard and Gustave Roussy, both of which see intimal sarcoma. Entry requires a molecular tumour board recommendation, so the route in is through a centre, not a direct application.
Trials in the same amplicon family, selected by histology
These recruit by diagnosis — usually dedifferentiated liposarcoma — but they test the same pathway. Several of them list intimal sarcoma or “soft-tissue sarcoma” broadly enough that it is worth asking.
| Trial | Population | Drug | Phase · where | Status |
|---|---|---|---|---|
| Mirdametinib + palbociclib NCT06843967 Memorial Sloan Kettering | Advanced liposarcoma including dedifferentiated and well-differentiated | MEK inhibitor + CDK4/6 inhibitor | Phase Ib/II · 7 centres, USA | Recruiting |
| Neoadjuvant abemaciclib + radiotherapy NCT06025747 University of Washington | High-risk adipocytic retroperitoneal sarcoma, before surgery | Abemaciclib + radiotherapy | Phase I · Seattle, USA | Recruiting |
| Sequential abemaciclib and gemcitabine NCT06498648 National Cancer Institute | Rb-positive sarcomas including dedifferentiated liposarcoma and leiomyosarcoma | Abemaciclib → gemcitabine/docetaxel | Phase I/II · USA | Recruiting |
| Doxorubicin ± pembrolizumab NCT06422806 National Cancer Institute | Metastatic or unresectable dedifferentiated liposarcoma and undifferentiated pleomorphic sarcoma | Doxorubicin ± pembrolizumab | Phase III · ~260 sites, USA | Recruiting |
| NRSTS2021 NCT06239272 St. Jude Children’s Research Hospital | Non-rhabdomyosarcoma soft-tissue sarcoma — the eligible histology list names intimal sarcoma explicitly | Risk-adapted surgery, radiotherapy, pazopanib, selinexor | Phase I/II · 7 centres, USA | Recruiting |
| Pemigatinib + retifanlimab NCT06389799 Lund University Hospital | Advanced dedifferentiated liposarcoma | FGFR inhibitor + PD-1 inhibitor | Phase II · 4 centres, Sweden | Recruiting |
Closed, but this is where the evidence came from
| Trial | What it showed | Status |
|---|---|---|
| SARC041 NCT04967521 | Abemaciclib vs placebo in 108 patients with advanced dedifferentiated liposarcoma: median progression-free survival 9.7 vs 1.5 months, HR 0.38 (90% CI 0.25–0.59), p<0.001. The first positive randomised phase III in this amplicon family.2 | Active, not recruiting |
| Abemaciclib phase II NCT02846987 | 30 patients with progressing dedifferentiated liposarcoma; median progression-free survival 33 weeks, 77% progression-free at 12 weeks.4 | Active, not recruiting |
| MANTRA | Milademetan (MDM2 inhibitor) vs the standard comparator chemotherapy in dedifferentiated liposarcoma — primary endpoint not met. The main reason MDM2 inhibitors remain second-order options.3 | Reported, negative |
How to approach a trial
- Get the molecular report in hand. MDM2 and CDK4 status by FISH or sequencing, Rb status, p53 status. Most of the trials above select on exactly these. Our page on what MDM2 and CDK4 amplification means explains each of them.
- Go through a sarcoma reference centre. Several trials — MegaMOST among them — require a molecular tumour board recommendation. A centre can also tell you about studies that are not yet in the public registry. Our list of centres and second opinions is a starting point.
- Open the registry entry and read the eligibility section, not just the summary. Prior lines of treatment, performance status and organ function exclude more people than the molecular criteria do.
- Ask about screening logistics early — archival tissue availability is a common stumbling block, especially in rare tumours where very little material was taken.
- Ask about expanded access if a drug exists but no trial is open near you.
Help us keep this current. If you find a trial that belongs here, or one that has closed, tell us — we will check it and update the page.
Frequently asked
What is a basket trial?
A basket trial enrols patients by molecular alteration rather than by tumour type. If a study selects on CDK4 amplification, a patient with intimal sarcoma, dedifferentiated liposarcoma or another amplified tumour may all be eligible for the same cohort.
Can I join a trial if my tumour is MDM2 amplified?
Possibly. Several open trials select on MDM2 amplification with wild-type p53, or on CDK4/CDK6 amplification with intact Rb, irrespective of histology. Eligibility is decided by the trial team on the basis of your pathology and molecular reports, prior treatments and general condition.
Are there trials in Europe for MDM2 or CDK4 amplified tumours?
Yes. MegaMOST, run from Centre Leon Berard with about ten French centres, has a cohort combining the MDM2 inhibitor siremadlin with the CDK4/6 inhibitor ribociclib for any advanced solid tumour with CDK4 or CDK6 amplification, intact Rb and wild-type p53. Entry requires a molecular tumour board recommendation.
Is abemaciclib approved for dedifferentiated liposarcoma?
The randomised phase III SARC041 trial reported a large progression-free survival benefit, but approval status differs by country and changes over time. Ask your treating centre what is currently available where you are treated.
How often is this page updated?
We re-check every trial listed here against the public registry and update the date at the top. If you spot something out of date, please tell us.
Sources
- ClinicalTrials.gov, U.S. National Library of Medicine. All trial records linked on this page were retrieved from the registry on 29 September 2026. clinicaltrials.gov.
- SARC041, randomised double-blind phase III, 108 patients. Abemaciclib versus placebo in advanced dedifferentiated liposarcoma: median progression-free survival 9.7 vs 1.5 months, HR 0.38 (90% CI 0.25–0.59), p<0.001. Presented at ASCO 2026. doi:10.1200/JCO.2026.44.17_suppl.LBA2.
- MANTRA, randomised phase III. Milademetan versus the standard comparator chemotherapy in dedifferentiated liposarcoma — primary endpoint not met. ESMO 2023. Ann Oncol 2023;34(suppl_2):LBA89.
- Phase II trial, 30 patients. Therapy-induced senescence contributes to the efficacy of abemaciclib in dedifferentiated liposarcoma; median progression-free survival 33 weeks. Clinical Cancer Research 2023. doi:10.1158/1078-0432.CCR-23-2378 (via PubMed, PMID 37695642).