ASCO 2026, taking place May 29–June 2 at McCormick Place in Chicago, Illinois, with online access, is expected to deliver practice-relevant updates across a broad range of malignancies. The program will highlight biomarker-driven treatment strategies, next-generation immunotherapy combinations, antibody-based and targeted platforms, perioperative optimization approaches, maintenance strategies, and long-term outcome analyses across multiple disease settings.
This article highlights top phase 3 immunotherapy trials to watch at ASCO 2026, spanning solid tumors and hematologic malignancies, including breast cancer, urothelial carcinoma, gastric cancer, melanoma, pancreatic cancer, and multiple myeloma. These studies explore novel combination strategies, tumor microenvironment modulation, precision-targeted immune approaches, and integration of immunotherapy across disease stages, with the potential to inform clinical practice and shape future standards of care in oncology.
Top Immunotherapy Trials to Watch at ASCO 2026
JCOG1919E (AMBITION) Phase III Trial: Paclitaxel + Bevacizumab With or Without Atezolizumab for Hormone Receptor–Positive / HER2-Negative Advanced Breast Cancer
This upcoming phase III abstract will be presented by First Author & Presenter Fumikata Hara, from Aichi Cancer Center Hospital.
The AMBITION (JCOG1919E) trial evaluates whether adding immunotherapy to a standard anti-angiogenic chemotherapy backbone improves outcomes in patients with hormone receptor–positive / HER2-negative advanced breast cancer, a subtype traditionally considered less immunogenic.
Study Concept
This study explores a triple-combination strategy integrating chemotherapy, anti-angiogenic therapy, and immune checkpoint inhibition:
- Paclitaxel → induces tumor cell death and antigen release
- Bevacizumab → inhibits angiogenesis and may normalize tumor vasculature
- Atezolizumab → restores T-cell–mediated anti-tumor immunity
The biological rationale centers on vascular normalization and immune priming, potentially converting an immunologically “cold” tumor into a more responsive microenvironment.
Why This Abstract Matters
- Targets HR+/HER2− breast cancer, where immunotherapy has shown limited benefit to date
- Evaluates a Phase III strategy to expand immunotherapy beyond TNBC
- Combines anti-angiogenesis with checkpoint blockade, a growing therapeutic paradigm
- Could redefine treatment approaches by unlocking immune responsiveness in low-immunogenic tumors
MAIN-CAV: Phase III Randomized Trial of Maintenance Cabozantinib + Avelumab vs Avelumab Alone After First-Line Platinum-Based Chemotherapy in Locally Advanced/Metastatic Urothelial Cancer (Alliance A032001)
This upcoming phase III abstract will be presented by First Author & Presenter Shilpa Gupta, from Cleveland Clinic Taussig Cancer Institute.
The MAIN-CAV trial evaluates whether adding a targeted therapy to standard avelumab maintenance improves outcomes in patients with locally advanced or metastatic urothelial carcinoma (la/mUC) following response or disease control with platinum-based chemotherapy.
Study Concept
This study investigates a maintenance intensification strategy combining immunotherapy with targeted therapy:
- Avelumab → standard-of-care maintenance after chemotherapy
- Cabozantinib → targets VEGFR, MET, and AXL pathways, influencing tumor growth and immune environment
Cabozantinib may enhance immunotherapy efficacy by:
- Modulating the tumor microenvironment
- Reducing immunosuppressive signaling
- Improving T-cell infiltration and activation
Why This Abstract Matters
- Builds on the JAVELIN Bladder 100 paradigm of maintenance immunotherapy
- Tests whether adding a TKI can deepen and prolong responses
- Represents a key step toward combination maintenance strategies in urothelial cancer
- Could redefine the post-chemotherapy standard of care in la/mUC
Immunotherapy for Urothelial Cancer: Types, Success Rate, Side Effects and More
Neoadjuvant/Adjuvant Serplulimab vs Placebo Combined With Chemotherapy for PD-L1–Positive Gastric Cancer: A Randomized, Double-Blind, Multicenter Phase III Study
This upcoming phase III abstract will be presented by First Author & Presenter Lin Shen, from Peking University Cancer Hospital.
This randomized, double-blind, multicenter study evaluates the addition of immunotherapy to perioperative chemotherapy in patients with PD-L1–positive gastric cancer, addressing a critical question in earlier-stage disease management.
Study Concept
This trial investigates a perioperative immunotherapy strategy integrating checkpoint blockade across both neoadjuvant and adjuvant settings:
- Serplulimab → enhances T-cell–mediated anti-tumor immunity
- Chemotherapy → induces tumor cell death and increases antigen presentation
The combination aims to:
- Prime the immune system before surgery
- Sustain immune surveillance after resection
- Improve long-term disease control in PD-L1–positive tumors
Why This Abstract Matters
- Expands immunotherapy into the perioperative gastric cancer setting
- Focuses on biomarker-selected (PD-L1+) patients
- Aligns with the shift toward early-stage immune intervention
- May help establish a new standard of care in resectable gastric cancer
Neoadjuvant Intralesional Daromun (L19IL2/L19TNF) in Resectable Locally Advanced Melanoma: Update on Primary Outcome and EFS Sensitivity Analyses From the PIVOTAL Phase III Trial
This upcoming phase III abstract will be presented by First Author & Presenter Katharina Kaehler, from University Hospital Schleswig-Holstein.
The PIVOTAL trial evaluates neoadjuvant intralesional immunotherapy in patients with resectable locally advanced melanoma, focusing on updated primary outcomes and event-free survival (EFS) analyses.
Study Concept
This study explores a localized immune activation strategy using intralesional therapy:
- Daromun → combines tumor-targeted IL-2 and TNF delivered directly into the tumor microenvironment
Mechanistically, this approach aims to:
- Induce strong local immune activation
- Promote T-cell infiltration and expansion
- Potentially trigger systemic anti-tumor immunity (abscopal effects)
Why This Abstract Matters
- Introduces intralesional immunotherapy in the neoadjuvant setting
- Represents a shift toward localized, tumor-directed immune modulation
- May offer an alternative to systemic therapy with reduced toxicity
- Expands the evolving landscape of perioperative immunotherapy in melanoma
Daratumumab + Bortezomib, Lenalidomide, and Dexamethasone (DVRd) in Newly Diagnosed Multiple Myeloma: Final Analysis of Transplant-Ineligible Patients From the Phase III CEPHEUS Study
This upcoming phase III abstract will be presented by First Author & Presenter Saad Usmani, from Memorial Sloan Kettering Cancer Center.
The CEPHEUS study reports final outcomes of daratumumab-based quadruplet therapy in patients with newly diagnosed multiple myeloma (NDMM) who are transplant-ineligible, a population with significant unmet clinical need.
Study Concept
This study evaluates a quadruplet immunotherapy-based regimen combining monoclonal antibody therapy with standard backbone treatment:
- Daratumumab → targets CD38 on myeloma cells, inducing immune-mediated cytotoxicity
- Bortezomib → disrupts protein degradation, leading to tumor cell apoptosis
- Lenalidomide → enhances immune activation and anti-tumor response
- Dexamethasone → provides anti-inflammatory and anti-myeloma effects
This combination represents a synergistic immunologic and cytotoxic approach, aiming to deepen responses and improve long-term outcomes.
Why This Abstract Matters
- Focuses on transplant-ineligible NDMM patients, a high-priority clinical population
- Evaluates quadruplet therapy, an emerging standard in myeloma
- Highlights the expanding role of CD38-targeted immunotherapy
- May further refine frontline treatment strategies and optimize long-term disease control