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Key Studies From Chicago 2024
An Expert’s Guide to ASCO 2024: Preview of the Top Abstracts

Released: May 30, 2024

Expiration: May 29, 2025

Allison Betof Warner
Allison Betof Warner, MD, PhD
Sara A. Hurvitz
Sara A. Hurvitz, MD, FACP
Kevin Kalinsky
Kevin Kalinsky, MD, MS
Shaji K. Kumar
Shaji K. Kumar, MD
Natasha Leighl
Natasha Leighl, MD, MMSc, FRCPC, FASCO
Zofia Piotrowska
Zofia Piotrowska, MD
Jeffrey P. Sharman
Jeffrey P. Sharman, MD
Eunice S. Wang
Eunice S. Wang, MD
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The 2024 American Society of Clinical Oncology (ASCO) Annual Meeting will feature significant results from numerous clinical studies in both solid tumors and hematologic malignancies. As part of CCO’s Independent Conference Coverage of ASCO 2024, oncology experts have identified their most anticipated abstracts, listed below. Remember to check the CCO website often as the meeting unfolds for downloadable slidesets summarizing the data from these studies and more. After the meeting, join us for our live, interactive “Conference to Clinic” webinar as experts discuss some of the most impactful abstracts presented during ASCO 2024 and answer audience questions on the data. Finally, read our CME-certified modules providing expert analyses and insights into the clinical implications of the new findings.

Top Picks: Breast Cancer

Sara Hurvitz, MD, FACP, and Kevin Kalinsky, MD, MS, identified the following as their top abstracts to watch.

  • DESTINY-Breast06: phase III study evaluating trastuzumab deruxtecan (T-DXd) compared with physician’s choice of chemotherapy in patients with hormone receptor (HR)–positive/HER2-low or HER2-ultralow metastatic breast cancer (MBC) following previous endocrine therapy (Abstract LBA1000). T-DXd is approved in patients with HER2-low metastatic disease, which is more prevalent in HR-positive than HR-negative disease. This study is investigating the potential role of T-DXd even earlier in the course of treatment including in a cohort of patients with HER2-ultralow disease.
  • postMONARCH: phase III trial comparing fulvestrant plus abemaciclib vs fulvestrant alone for HR-positive/HER2-negative advanced disease following progression on previous CDK4/6 inhibitor plus endocrine therapy (Abstract LBA1001). Randomized phase II trials have shown inconsistent benefit of continuing a CDK4/6 inhibitor and switching endocrine therapy after progression on a CDK4/6 inhibitor. This is the first phase III trial to address this strategy. 
  • SACI-IO HR+: a randomized phase II trial of sacituzumab govitecan with or without pembrolizumab in HR-positive/HER2-negative MBC (Abstract LBA1004). Results from this study will help address whether there is an additive effect of combining an antibody–drug conjugate (ADC) plus immunotherapy in advanced HR-positive disease. 
  • DESTINY-Breast07: results from an interim analysis of this phase Ib/II study with cohorts assessing the safety and antitumor activity of T-DXd with or without pertuzumab as first-line therapy for HER2-positive MBC (Abstract 1009).
  • A-BRAVE: investigator-driven phase III study comparing adjuvant avelumab vs observation in patients with early-stage triple-negative breast cancer with residual disease after neoadjuvant chemotherapy or at high risk of relapse following primary surgery and adjuvant chemotherapy (Abstract LBA500). Trials of immunotherapy in early-stage triple-negative breast cancer will help further define the treatment algorithm for these patients.
  • I-SPY2.2: results from an analysis of pathologic complete response with neoadjuvant datopotamab deruxtecan plus durvalumab (Abstract LBA501). This is the first report of this ADC in the neoadjuvant setting here with an immune checkpoint inhibitor and alone in a separate study (Abstract LBA509); these studies will demonstrate whether there is an antitumor signal with this approach.

Additional studies to watch in breast cancer include:

  • NATALEE: a subgroup analysis of adjuvant ribociclib plus nonsteroidal aromatase inhibitors vs nonsteroidal aromatase inhibitors alone in patients with N0 HR-positive/HER2-negative early breast cancer (Abstract 512).

Top Picks: Hematologic Malignancies
Several interesting and potentially practice-changing studies in hematologic malignancies are being reported at ASCO 2024.

Eunice S. Wang, MD, identified top abstracts to watch in the area of myelodysplastic syndromes (MDS) and leukemias at ASCO 2024.

  • ASC4FIRST: primary results from the pivotal phase III study of asciminib vs investigator-selected tyrosine kinase (TKI) inhibitors, including imatinib and second-generation TKIs, in newly diagnosed patients with chronic myeloid leukemia (CML) (Abstract LBA6500). This is the first head-to-head trial comparing asciminib with all standards of care for patients with newly diagnosed CML. Asciminib has previously demonstrated statistically superior major molecular response rate and a favorable safety and tolerability profile compared with other TKIs in CML, and it has the potential to move into the frontline setting as a preferred TKI for newly diagnosed patients with CML.
  • MANIFEST-2: updated efficacy and safety results from a phase III study of pelabresib (CPI-0610), an investigational, oral, small molecule BET inhibitor, in combination with ruxolitinib for patients with JAK inhibitor–naive myelofibrosis (Abstract 6502). The combination of pelabresib and ruxolitinib was superior to ruxolitinib alone in shrinking spleen size with a trend toward improved symptoms and anemia management as compared with ruxolitinib alone. These results support pelabresib as a potential new standard of care for patients with myelofibrosis in the future.
  • FELIX: open-label, single-arm phase Ib/II study of obecabtagene autoleucel (obe-cel, a novel, investigational, fast off-rate anti-CD19 autologous CAR T-cell therapy for adult patients with relapsed/refractory (R/R) B-cell acute lymphoblastic leukemia (ALL) (Abstract 6504). The FELIX trial demonstrated impressive event-free and overall survival results with a median follow-up of 16.6 months. The promising results support obe-cel as a potential next standard of care CAR T-cell therapy for patients with R/R B-cell ALL. 
  • A multisite randomized trial of a collaborative palliative and oncology care model for patients with acute myeloid leukemia and MDS receiving nonintensive chemotherapy evaluating the value of monthly outpatient palliative care visits and twice-weekly palliative care visits during hospitalizations (Abstract LBA6508). As previously reported, the institution of these palliative care interventions significantly improved rates and timing of discussion and documentation of end-of-life care preferences, reduced hospitalizations, and improved quality of life.

In multiple myeloma (MM), Shaji Kumar, MD, identified the following abstracts to watch.

  • BENEFIT/IFM2020-05: a randomized phase III trial assessing a CD38 mAb combination with or without bortezomib in patients with newly diagnosed MM eligible for autologous stem cell transplant (ASCT) (Abstract 7501). This report suggests significantly improved rate of complete response and measurable residual disease (MRD) negativity with isatuximab and bortezomib plus lenalidomide/dexamethasone (Rd) vs isatuximab plus Rd.
  • IMROZ: a randomized phase III trial of isatuximab plus bortezomib/RD (VRd) vs VRd for ASCT-ineligible patients with newly diagnosed MM (Abstract 7500). In patients not eligible for transplant because of older age or comorbidities, this report shows a significant improvement in risk of progression or death with the quadruplet therapy vs standard-of-care triplet therapy.
  • PERSEUS: updated results from this phase III trial of subcutaneous daratumumab plus VRd followed by lenalidomide/daratumumab maintenance vs VRd followed by lenalidomide maintenance, along with ASCT, in patients with newly diagnosed MM (Abstract 7502). In this analysis, deepening of response and MRD negativity during the maintenance phase of the study is reported with the addition of daratumumab.
  • DREAMM-8: a randomized phase III study of the BCMA-targeted ADC belantamab mafodotin plus pomalidomide/dexamethasone vs pomalidomide/bortezomib/dexamethasone in patients with R/R MM (Abstract LBA105). Highly anticipated results from this randomized phase III trial will be presented as a late-breaking abstract.

For lymphomas, Jeff Sharman, MD, has identified the following abstracts of special interest to look for at ASCO 2024.

  • DEB: interim analysis of a phase III study of tucidinostat plus rituximab plus cyclophosphamide/doxorubicin/vincristine/prednisone (R-CHOP) in previously untreated diffuse large B-cell lymphoma (DLBCL) with double expression of MYC and BCL2 (Abstract LBA7003). Tucidinostat, an oral HDAC inhibitor, has been evaluated in a prospective, randomized phase III study among patients with DLBCL and expression of both MYC and BCL2. Although not limited exclusively to the double-hit population, double expression has been associated with inferior outcomes with standard R-CHOP. This late-breaking abstract presentation will report results from an interim analysis.
  • ECHELON-3: results from the phase III trial of brentuximab vedotin plus lenalidomide and rituximab in patients with R/R DLBCL (Abstract LBA7005). Prior studies in DLBCL have shown that CD30 expression is not required for activity of brentuximab in the treatment of the disease.  This randomized phase III study compared lenalidomide/rituximab with or without brentuximab, and results will inform on the benefit of this combination strategy with the data being presented in a late-breaking abstract.

Additional studies to watch in hematologic malignancies include:

  • Combination of pirtobrutinib and lentiviral transduced bispecific anti-CD20/CD19 (LV20.19) CAR T-cell therapy to improve outcomes in patients with R/R lymphoma (Abstract 7043). 
  • Secondary myeloid malignancy after CAR T-cell therapy for non-Hodgkin lymphoma (Abstract 7033).
  • Factors before leukapheresis that correlate with severe cytopenia and therapy-related myeloid neoplasm post CAR T-cell therapy (Abstract 7038).

Top Picks: Lung Cancer
In lung cancer, Zofia Piotrowska, MD, MHS, and Natasha Leighl, MD, MMSc, FRCPC, FASCO, have identified several late-breaking abstracts of interest at ASCO 2024, along with many other interesting studies being reported.

  • ADRIATIC: phase III trial investigating durvalumab as consolidation treatment for patients with limited-stage small-cell lung cancer (LS-SCLC) (Abstract LBA5). This important study may be the first in a very long time to bring progress to LS-SCLC potentially adding durvalumab to our armamentarium of curative options for patients with LS-SCLC. We have already seen improved outcomes with durvalumab and atezolizumab in patients with extensive-stage SCLC. ADRIATIC may expand the role of immunotherapy, in the early-stage setting similar to what has become our standard approach in non-small-cell lung cancer (NSCLC) (with the PACIFIC regimen). ADRIATIC has the potential to rapidly change clinical practice.
  • LAURA: phase III trial of osimertinib after definitive chemoradiotherapy in patients with unresectable stage III EGFR-mutated NSCLC (Abstract LBA4). The LAURA trial is among the most eagerly awaited NSCLC trials of ASCO 2024. If positive, this study may help us improve outcomes beyond the PACIFIC regimen or chemoradiation alone. Results of LAURA have the potential to change clinical practice by filling the last remaining gap where EGFR TKIs have not yet become a standard of care—unresectable stage III disease—and bringing a targeted approach with third-generation TKIs from stage IB to stage IV.
  • We are also excited about a study comparing the effectiveness of early palliative care delivered via telehealth vs in person among patients with advanced lung cancer (Abstract LBA3). Building upon previous studies that have demonstrated meaningful improvement in patient quality of life and survival with early incorporation of palliative care in patients with metastatic lung cancer, this study asks a practical question of whether this care can be delivered in a virtual format. During the pandemic, we learned that many aspects of care can be delivered via telehealth or other means, thereby promoting patient convenience, allowing greater access to care for those who live far from cancer centers, and reducing treatment burden. This will be an important tool to integrate across all systems and will have important implications for both medical oncologists and palliative healthcare professionals.

Additional studies to watch in lung cancer include:

  • EVOKE-01: primary results of a phase III trial evaluating sacituzumab govitecan vs docetaxel in patients metastatic NSCLC previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors (Abstract LBA8500). This study is important to help us learn how to move forward with TROP-2 ADCs in lung cancer. Future combinations with checkpoint inhibitors and further development in selected subgroups (eg, those with oncogene-addicted cancers) may be important next steps in TROP-2 ADCs development. 
  • CROWN: 5-year progression-free survival and safety update of a phase III trial comparing lorlatinib with crizotinib for the treatment-naive patients with advanced ALK-positive NSCLC (Abstract LBA8503). 
  • PALOMA-3: primary results of a phase III trial comparing subcutaneous or intravenous amivantamab, both in combination with lazertinib in EGFR-mutated, advanced NSCLC (Abstract LBA8505).
  • KRYSTAL-12: phase III study of adagrasib vs docetaxel in previously treated advanced or metastatic KRASG12C-mutated NSCLC (Abstract LBA8509). This study may help to establish adagrasib over docetaxel as second-line treatment for patients with KRASG12C-mutated NSCLC.
  • Beamion LUNG-1: updates from a phase Ia/Ib trial of the HER2-specific TKI zongertinib (BI 1810631) in patients with HER2 aberration-positive solid tumors (Abstract 8514).
  • WU-KONG1: primary analysis of a multinational, pivotal phase II study of the EGFR inhibitor sunvozertinib in platinum pretreated NSCLC with EGFR exon 20 insertion mutations (Abstract 8513). 
  • DESTINY-Lung02: final analysis of a phase II trial investigating T-DXd in HER2-mutated metastatic NSCLC (Abstract 8543).

Top Picks: Skin Cancer
Allison Betof Warner, MD, PhD, has identified a few key studies of interest at ASCO 2024.

  • NADINA: a randomized phase III trial assessing neoadjuvant nivolumab plus ipilimumab vs adjuvant nivolumab in resectable stage III melanoma (Abstract LBA2).
  • RELATIVITY-048: first analysis from a nonrandomized phase I/II trial of the triplet regimen of nivolumab plus relatlimab plus ipilimumab in the cohort of patients with advanced melanoma (Abstract 9504).
  • IOV-COM-202: updated results of the combination of lifileucel autologous tumor-infiltrating lymphocyte therapy with pembrolizumab as first-line therapy for patients with advanced melanoma (Abstract 9505).
  • IGNYTE: updated results from a phase I/II study of RP1, an HSV-1–based oncolytic immunotherapy expressing granulocyte-macrophage colony-stimulating factor and the fusogenic protein GALV-GP-R- in patients with advanced melanoma after failure of anti–PD-1 therapy with or without anti–CTLA-4 therapy (Abstract 9517).
  • KEYNOTE-942: 3-year update of this trial of individualized neoantigen therapy mRNA-4157 (V940) with pembrolizumab in patients with resected melanoma (Abstract 9512).

Additional studies to watch in genitourinary cancers include:

  • Initial phase I/II results of ARV-766, a novel proteolysis targeting chimera (PROTAC) AR degrader active against wild-type and mutant AR in patients with metastatic castration-resistant prostate cancer (mCRPC) receiving androgen deprivation therapy who progressed after at least 1 androgen receptor pathway inhibitor (Abstract 5011).
  • An exploratory analysis of baseline circulating tumor DNA and outcomes in taxane-naive patients with prostate-specific membrane antigen–positive mCRPC who were treated with 177Lu-PSMA-617 vs androgen receptor pathway inhibitor switch in the registrational phase III PSMAfore trial, which met its primary endpoint of radiologic progression-free survival (Abstract 5008). 

 

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