ASCO 2025 Highlights: Critical Advancements in Precision Oncology

Day 2 highlights: Saturday 31st May

Future of Multi-Cancer Detection (MCD) Tests in Cancer Screening

Speakers emphasized the transformative potential of multi-cancer detection (MCD) tests in revolutionizing cancer screening. These tests identify cancer-related biological signatures in blood. Advanced algorithms powered by machine learning or AI are used to predict the tissue of origin. These biological signatures include DNA fragments, methylation, RNA, or proteins.

Another highlight was the critical balance between high specificity to avoid false positives and high sensitivity to detect cancers. MCD tests represent the initial step in a comprehensive screening program. Success factors hinge on sensitivity, timely evaluation, early-stage disease curability, and screening accessibility. The session concluded that while MCD tests could redefine the screening paradigm, it is crucial to recognize that screening is a multistep process. It requires robust evidence from randomized trials to ensure safety and efficacy.

Pioneering the Future of Cancer Treatment: The Transition of Gene Therapy into Solid Tumors Lessons from Gene Therapies Adopted in Inherited Diseases

Gene therapy for solid tumors is now a clinical reality. With continued regulatory collaboration and stakeholder engagement, these therapies are poised to redefine standards of care and expand access for patients worldwide. Recent FDA approvals and clinical breakthroughs make way for a new era of precision oncology. And T cell therapies are delivering real-world impact.

Breakthrough Therapies, Real-World Impact:

• Afami-cel: The first FDA-approved TCR therapy targeting MAGE-A4. This marks a pivotal moment in the treatment of synovial sarcoma.
• Lete-cel: Targeting NY-ESO-1, demonstrates strong clinical potential in both synovial sarcoma and myxoid round-cell liposarcoma. This reinforces the viability of TCR therapies in solid tumors.
• Lifileucel: A TIL therapy, has gained FDA approval for metastatic melanoma. It validates the clinical utility of tumor-infiltrating lymphocyte approaches.

The afternoon session on gene therapy drew lessons from hereditary diseases. It gave focus to the life-changing successes of exa-cel gene therapy in sickle cell anemia. However, it also emphasized the often-prohibitive limitations of gene therapy treatments.

These included:

• Very high costs
• Limited scalability and access (especially in patient populations who would benefit most)
• Long manufacturing times
• Severe toxicities

Promising alternatives are being developed by MD Anderson Cancer Center. Natural killer (NK) cell therapies mean off-the-shelf treatments derived from donors or cell lines can be developed. This enables faster, more scalable production, with lower toxicity profiles. And is able to reduce the overall cost of treatment.

Evolution of Kidney Cancer Biomarkers

Another hot topic was the evolution of biomarkers in kidney cancer over the last decade. Advancements showcased imaging, blood-based biomarkers for detecting minimal residual disease, and emerging gene expression signatures like single-cell sequencing and spatial biology. These tools have helped subtype clear cell renal cell carcinomas and predict treatment responses, with ongoing trials aiming to improve outcomes.

Various new biomarkers in kidney cancer include:

• Serum KIM1, which has the potential to be a significant predictor of treatment outcomes with atezolizumab in high-risk resected renal cell carcinoma (RCC).
• The development of a machine learning-based model that integrates diverse biomarkers. These include PD-L1 score, AI platform analysis of images, and examination of extracellular matrix (ECM) factors.

However, several limitations were acknowledged. For example, the need for extensive validation and incorporation of extra features like transcriptional state and genetics. Researchers exploring the microtome of RCC showed the importance of circulating MAdCAM-1 levels as a prognostic biomarker in metastatic RCC. Research suggested that patients with low MAdCAM-1 levels may benefit from microbiota-centered interventions.

Finally, the potential to induce significant pathologic responses in a subset of patients with high-risk RCC, leading to improved disease-free survival, was highlighted. The presence of CD8+CD39+ T-cells following neoadjuvant avelumab and axitinib may be a valuable predictive biomarker for treatment outcomes.

Day 3 highlights: Sunday 1st June

Plenary Session: Phase 3 ATOMIC trial evolving Colon Cancer Treatment with Atezolizumab

Results of randomized trial of standard chemotherapy alone or combined with atezolizumab as adjuvant therapy for patients with stage III deficient DNA mismatch repair (dMMR) colon cancer (Alliance A021502; ATOMIC).

Atezolizumab, combined with mFOLFOX6 chemotherapy, is set to transform the treatment landscape for stage III colon cancer with deficient mismatch repair (dMMR).

• Patients receiving atezolizumab with mFOLFOX6 showed a significant improvement in Disease-Free Survival (DFS). A three-year DFS rate of 86.4% was compared to 76.6% for the chemotherapy-alone group.
• The efficacy of atezolizumab was consistent across various subgroups. It highlights the broad applicability of this approach.
• Atezolizumab combined with mFOLFOX6 was well tolerated, with manageable adverse events.
• Atezolizumab with mFOLFOX6 therapy represents a new era in colon cancer therapy. It offers hope for better outcomes and a brighter future for patients.

Potential new standard treatment in resected head and neck squamous cell carcinoma for the first time in two decades

Results of NIVOPOSTOP (GORTEC 2018-01): A phase III randomized trial of adjuvant nivolumab added to radio-chemotherapy in patients with resected head and neck squamous cell carcinoma at high risk of relapse.

Nivolumab, combined with cisplatin-radiotherapy (CRT), is set to change the treatment landscape for resected locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN). The Phase 3 NIVOPOSTOP study has demonstrated that this combination significantly improves disease-free survival (DFS) compared to the current standard of care.

• Patients receiving nivolumab with CRT showed a significant improvement in DFS. A three-year DFS rate of 63.1% was compared to 52.5% for the CRT-alone group.
• The efficacy of nivolumab was consistent across various subgroups. The data highlight the broad applicability of this approach.
• Nivolumab combined with CRT was well tolerated. There were fewer grade 4 adverse events compared to CRT alone.
• Nivolumab represents a new era in head and neck cancer therapy. This offers hope for better outcomes and a brighter future for patients.

Transforming Polycythemia Vera Treatment with Rusfertide

Results from Part 1a of VERIFY, a phase 3, double-blind, placebo (PBO)-controlled study of rusfertide for treatment of polycythemia vera (PV).

Polycythemia vera (PV) is a condition characterized by the overproduction of red blood cells. Rusfertide is a new, self-injected peptide that mimics hepcidin and reduces erythrocytosis. The VERIFY study is a global phase 3 trial assessing Rusfertide versus placebo (PBO) in patients with PV requiring frequent phlebotomies.

Review of study concluded that Rusfertide is revolutionizing the management of PV. This innovative therapy has shown significant promise in Part 1a of the phase 3 VERIFY study. So far, it is meeting primary and all key secondary endpoints. Patients treated with Rusfertide experienced:

• A substantial reduction in the need for phlebotomies
• Improved hematocrit control
• Significant improvements in fatigue and symptom scores

As we look to the future:

• Additional data from longer-term follow-up will further solidify Rusfertide's role in PV treatment.
• This groundbreaking therapy offers new hope for patients. It aims to reduce the need for cytoreduction and potentially lower the risk of progression to more severe conditions like myelofibrosis or acute myeloid leukemia.

Camizestrant represents a new era in personalized breast cancer therapy, offering hope for better outcomes

Results of Camizestrant + CDK4/6 inhibitor (CDK4/6i) for the treatment of emergent ESR1 mutations during first line (1L) endocrine-based therapy (ET) and ahead of disease progression in patients (pts) with HR+/HER2– advanced breast cancer (ABC): Phase 3, double-blind ctDNA-guided SERENA-6 trial.

Camizestrant, combined with CDK4/6 inhibitors, is set to transform the treatment landscape for HR+/HER2– advanced breast cancer. The groundbreaking SERENA-6 trial has demonstrated that using ctDNA to detect ESR1 mutations and guide therapy changes can significantly improve progression-free survival (PFS) for patients.

• Patients switching to camizestrant showed a median PFS of 16.0 months. This is nearly double the 9.2 months seen with continued AI therapy.
• The PFS advantage was observed across all patient subgroups. It highlighted the broad applicability of this approach.
• Camizestrant was well tolerated, with a safety profile consistent with existing treatments.

Revolutionizing Gastric Cancer Treatment with Durvalumab

Results of event-free survival (EFS) in MATTERHORN: A randomized, phase 3 study of durvalumab plus 5-fluorouracil, leucovorin, oxaliplatin and docetaxel chemotherapy (FLOT) in resectable gastric/gastroesophageal junction cancer (GC/GEJC).

Durvalumab combined with FLOT chemotherapy is set to transform the treatment landscape for resectable gastric and gastroesophageal junction cancer (GC/GEJC). The MATTERHORN study has demonstrated that this combination significantly improves event-free survival (EFS) compared to the current standard of care.

• Patients receiving durvalumab with FLOT showed a significant improvement in EFS. The median EFS has not yet been reached, compared to 32.8 months for the placebo group.
• The 24-month EFS rate was higher for the durvalumab group. This highlights the long-term benefits of this combination.
• Durvalumab combined with FLOT was well tolerated. The reported adverse event rates are similar to the placebo group.

Durvalumab represents a new era in gastric cancer therapy, offering hope for better outcomes and a brighter future for patients.

Considerations for treating physicians specializing in precision oncology

Should we offer for all? The consensus is to offer the treatment to all patients. There is no subgroup to exclude, and it is recommended for all PD-L1 subgroups.

Will OS be positive? While the MATTERHORN study's answer is "TBD," a promising curve shape and a strong design with a p-value threshold of 0.049 at final analysis.

Day 4 highlights: Monday 2nd June

Revolutionizing Cancer Treatment: The Latest Breakthroughs in Antibody Drug Conjugates at ASCO

Results of Safety and efficacy of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in high-grade neuroendocrine neoplasms.

(Abstract 105)

SEZ6 is a marker found in small cell lung cancer (SCLC) and high-grade neuroendocrine neoplasms (NENs). There is a need for new targeted therapies for NENs. ABBV-706 is an antibody-drug conjugate targeting SEZ6. It is in a phase 1 study for patients with advanced solid tumors. Early results showed it is safe and effective in SCLC and NENs.

ABBV-706 showed promising efficacy in high-grade NENs, supporting further development in specific subtypes.

Results of Phase 1 study of SHR-1826, a c-MET–directed antibody-drug-conjugate (ADC), in advanced solid tumors.

(Abstract 106)

MET alterations are significant drivers of cancer processes, including tumor invasion, growth, and metastasis, leading to poor prognosis. SHR-1826 is an antibody-drug conjugate (ADC) targeting c-MET, attached to a potent topoisomerase I inhibitor. This first-in-human phase 1 trial evaluates SHR-1826 in patients with advanced solid tumors.

SHR-1826 demonstrated a manageable safety profile and promising anti-cancer activity in patients with heavily pretreated advanced solid tumors, particularly MET-altered NSCLC. These results warrant further investigation in this population.

Results of phase 1 trial of SHR-A2102, a nectin-4–directed antibody drug conjugate (ADC), in advanced solid tumors.

(Abstract 107)

Nectin-4 is a cell adhesion molecule that is highly expressed in a wide variety of cancers and is associated with poor prognosis. SHR-A2102 is a novel ADC consisting of a fully humanized Nectin-4–directed monoclonal antibody, bound to topoisomerase I inhibitor payload via a cleavable linker. SHR-A2102 demonstrated a manageable safety profile and promising activity across a variety of pretreated advanced solid tumors. Multiple trials are ongoing to further assess SHR-A2102 both as monotherapy and in combination therapy for solid tumors.

Transformative power in Gynecologic Oncology: The Power of Antibody Drug Conjugates

Antibody Drug Conjugates (ADCs) are transforming the landscape of gynecologic oncology. With innovative targets like HER2, TROP2, FRα, TF, Nectin-4, B7H3, and B7H4, and various payloads, ADCs are delivering unprecedented objective response rates. From the FDA-approved Mirvetuximab soravtansine for ovarian cancer and Trastuzumab deruxtecan for pan-cancer, these therapies are paving the way for more personalized and effective treatments. Stay ahead in the fight against gynecologic cancers with the latest advancements in ADC technology.

Summarized Strategic Next Steps for ADC

Leverage existing technologies such as immunohistochemistry (IHC) and next-generation sequencing (NGS) to test for new biomarkers like c-MET, SEZ6, and Nectin-4. These technologies are already well-established in clinical laboratories and can be adapted for new biomarkers.

Take into consideration the amount of material available in target diseases to allow biomarker testing. In highly competitive disease spaces, such as NSCLC, consider NGS testing. This allows analysis of multiple targets at once.

3. Diagnostic Partner Selection

Collaborate with diagnostic companies that have expertise in biomarker testing. This can provide comprehensive solutions, including assay development, validation, and regulatory support. Partnerships can facilitate the rapid adoption of new biomarkers in clinical practice.

Consider the impact of introducing new biomarker tests on testing laboratories. Include the availability of technology, expertise in biomarker testing/analysis, education requirements, workload, and burden of assay verification.

Engage with regulatory bodies to ensure that new biomarker tests meet the necessary standards for approval. Work with payers to secure reimbursement for these tests to make them accessible to a broader patient population.

Continue research to improve understanding of the role of these biomarkers in cancer progression and treatment response. Invest in clinical trials to generate robust data supporting the efficacy and safety of targeted therapies based on these biomarkers.

By following these strategic steps, the pharmaceutical industry can effectively introduce new biomarkers in cancer. From here, it can better enhance personalized treatment approaches and improve patient outcomes.