Below, we feature six cancer clinical trials that opened for patient enrollment in 2025, conducted by the ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) with support from the National Cancer Institute, one of the National Institutes of Health. These trials aim to enhance outcomes for patients by improving upon standard treatments. Click on the links for each trial to learn more.

Bladder Cancer

EA8231 - A Phase 3 Randomized Trial of Pembrolizumab in Combination with Sacituzumab Govitecan vs. Standard of Care in Anti-PD(L)1-Resistant Advanced Urothelial Cancer

Although front-line therapies for urothelial cancer continue to improve, survival rates for locally advanced and metastatic disease remain low, and there is a critical need for more effective treatments. Early studies have shown promising results for the targeted therapy sacituzumab govitecan in this setting. In particular, the combination of sacituzumab govitecan and pembrolizumab immunotherapy may be effective for patients with PD-L1-positive cancers.

EA8231 is evaluating this combination in patients with advanced urothelial cancer. Investigators hypothesize that treatment with sacituzumab govitecan and pembrolizumab will improve survival outcomes compared to the standard-of-care salvage therapy alone. The study’s primary endpoint is overall survival.

This study is led by Monika Joshi, MD (Penn State Cancer Institute). Learn more about EA8231 at ecog-acrin.org. For inquiries, email the study team.

Lung Cancer

EA5231/CLEAR – A Randomized Phase 3 Trial of Checkpoint Blockade in Lung Cancer Patients in the Adjuvant Setting Based on Pathologic Response Following Neoadjuvant Therapy

Nearly 80% of patients with non-small cell lung cancer (NSCLC) do not have a pathologic complete response (pCR) from treatment before surgery, which leaves them at high risk of recurrence. Researchers believe that the absence of pCR signifies resistance to single-agent immune checkpoint inhibitors, such as durvalumab, which are commonly given as adjuvant therapy. However, an investigational targeted therapy, ceralasertib, has been shown to enhance the efficacy of durvalumab immunotherapy in other studies of patients with advanced NSCLC. Durvalumab is already US Food and Drug Administration (FDA) approved as a standalone adjuvant therapy for NSCLC.

CLEAR is a randomized phase 3 trial for patients with stage 2 to select 3B NSCLC who did not reach pCR after neoadjuvant therapy. Investigators hypothesize that adding ceralasertib to adjuvant durvalumab will improve survival outcomes compared to durvalumab alone. The study’s primary endpoint is disease-free survival.

This study is led by Dwight H. Owen, MD, MSc (The Ohio State University Comprehensive Cancer Center). Learn more about EA5231/CLEAR at ecog-acrin.org. For inquiries, email the study team.

Lymphoma

EA4231 – A Phase 2 Study of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid (ViPOR) in Relapsed or Refractory CD10-Negative Diffuse Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma with MYC and BCL2 Rearrangements

While current standard-of-care therapies can lead to long-lasting remission of B-cell lymphoma, about 40% of patients will face a relapse or treatment resistance. In these cases, the cancer is particularly difficult to treat, and survival outcomes are poor. In recent years, researchers have developed new targeted therapies—but these drugs rarely produce lasting responses because the tumors can become resistant. Combining targeted drugs that block multiple pathways has the potential to overcome mechanisms of resistance.

An early-phase study at the National Cancer Institute tested a five-drug combination without chemotherapy, known as ViPOR (venetoclax, ibrutinib, prednisone, obinutuzumab, and lenalidomide). The regimen was shown to be safe and potentially effective for patients with certain lymphoma subtypes:

• CD10-negative diffuse large B-cell lymphoma
• High-grade B-cell lymphoma with MYC and BCL2 rearrangements

EA4231 seeks to confirm these findings in a single-arm phase 2 trial. The study’s primary endpoint is complete response rate.

This study is led by Christopher J. Melani, MD (National Cancer Institute). Learn more about EA4231 at ecog-acrin.org. For inquiries, email the study team.

Lymphoma

EA4232 – A Randomized Phase 3 Study to Evaluate Benefits of Autologous Stem Cell Transplant in Patients with Peripheral T Cell Lymphoma That Achieved a First Complete Remission (CR1) Following Induction Therapy (PTCL-STAT)

While prognoses for peripheral T-cell lymphoma (PTCL) vary depending on subtype, stage, and other factors, the overall 5-year survival rate is low at approximately 30-40%. Although many patients reach remission with initial therapy, relapses are all too common for this rare and aggressive form of non-Hodgkin lymphoma. Consolidation therapy is often given to eliminate any remaining cancer and prevent recurrence or relapse. One consolidation therapy option for patients who are physically fit enough to withstand the difficult procedure is an autologous stem cell transplant (ASCT), which involves high-dose chemotherapy followed by re-infusion of patients’ own blood stem cells. However, the benefit of this approach for these patients is heavily debated due to conflicting results from previous trials. Plus, ASCT has never been evaluated in a randomized controlled trial.

EA4232 is the first randomized controlled phase 3 trial to address this knowledge gap. The study is enrolling patients with radiologic complete response (CR) after induction therapy with an anthracycline-based regimen. Participants will be randomized to receive either standard-of-care observation (PET-CT or CT imaging) or ASCT, given per standard institutional practice. Investigators hypothesize that treatment with ASCT will improve progression-free survival (PFS) compared to observation alone.

This study is led by N. Nora Bennani, MD (Mayo Clinic). Learn more about EA4232 at ecog-acrin.org. For inquiries, email the study team.

Myeloma

EAA241 - A Randomized Phase 2 Trial Comparing Daratumumab-Bortezomib-Dexamethasone versus Cyclophosphamide-Bortezomib-Dexamethasone in Newly Diagnosed Multiple Myeloma with Light Chain Cast Nephropathy

Patients with multiple myeloma and acute renal failure caused by light chain cast nephropathy (LCCN) often face limited treatment options and delayed access to novel drugs due to their compromised kidney function. They are also routinely excluded from clinical trials. As a result, they may have lower survival rates than other myeloma patients, and there is no universal consensus on management among myeloma specialists in the US.

The EAA241 trial aims to address this knowledge gap. Investigators hypothesize that incorporating daratumumab, a novel targeted therapy, into timely treatment may be the key to reversing kidney failure. Recovery of kidney function may allow treatment to be more effective, potentially improving survival. Patients in the study will receive one of two regimens: cyclophosphamide-bortezomib-dexamethasone (the most common regimen currently in use) or daratumumab-hyaluronidase-bortezomib-dexamethasone. The study’s primary endpoint is renal response rate.

This study is led by Amany Keruakous, MD, MS (Augusta University Medical Center). Learn more about EAA241 at ecog-acrin.org. For inquiries, email the study team.

Stomach Cancer

EA2234/STOPGAP II - A Randomized Phase 2/3 Trial of Intraperitoneal Paclitaxel Plus Systemic Treatment vs. Systemic Treatment Alone in Gastric Carcinomatosis

Gastric carcinomatosis is an advanced stage of stomach cancer, and the prognosis is poor, even with the best available systemic therapies. New and more effective treatment strategies are urgently needed. The STOPGAP II clinical trial (EA2234) is evaluating a possible new approach combining systemic and local therapy. A common localized therapy is paclitaxel chemotherapy given with NIPEC (normothermic intraperitoneal chemotherapy), which delivers the drug directly to the peritoneal cavity.

STOPGAP II study investigators hypothesize that adding paclitaxel with NIPEC to standard-of-care systemic therapy will improve survival outcomes compared to systemic therapy alone. The trial’s primary endpoints are progression-free survival (PFS) for phase 2 and overall survival for phase 3. At the time of opening in August 2025, STOPGAP II was the only randomized clinical trial for patients with gastric carcinomatosis in the United States (US).

This study is led by Maheswari Senthil, MD (University of California, Irvine). Learn more about EA2234/STOPGAP II at ecog-acrin.org. For inquiries, email the study team.