OncLive® On Air

In today’s episode, we welcomed Douglas W. Sborov, MD, MS, to discuss the significance of the July 2026 FDA approval of isatuximab-irfc (Sarclisa Escena) for subcutaneous injection for multiple myeloma indications. Dr Sborov is a tenured professor of medicine in the Department of Internal Medicine in the Division of Hematology and Hematologic Malignancies and an adjunct associate professor in the Departments of Molecular Pharmaceutics and Biomedical Engineering at the University of Utah Huntsman Cancer Institute (HCI) in Salt Lake City, as well as director of the HCI Hematology Disease Center and Plasma Cell Dyscrasias (PCD) Program, co-leader of the Hematologic Malignancies Clinical Trials Research Group, and member of the HCI Experimental Therapeutics Program and International Myeloma Working Group (IMWG).
As part of the July 10, 2026, approval, subcutaneous isatuximab is indicated for use:

in combination with pomalidomide (Pomalyst) and dexamethasone for the treatment of adult patients with multiple myeloma who have received at least 1 prior line of therapy, including lenalidomide (Revlimid) and a proteasome inhibitor

in combination with carfilzomib (Kyprolis) and dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy

in combination with bortezomib (Velcade), lenalidomide, and dexamethasone for the treatment of adult patients with newly diagnosed multiple myeloma who are not eligible for an autologous stem cell transplant

In our exclusive interview, Dr Sborov outlined how the subcutaneous formulation of isatuximab and the ability to administer the agent via an on-body delivery system could affect patient quality of life. He also detailed key findings from the phase 3 IRAKLIA trial (NCT05405166) that supported the approval and explained how the use of isatuximab may shift in clinical practice following the subcutaneous approval.

In today's episode, we spoke with Solange Peters, MD, PhD. Dr Peters is a full professor, and chair of medical oncology and the thoracic malignancies programme in the Department of Oncology at the University Hospital of Lausanne in Switzerland. 
In our exclusive interview, Dr Peters discussed the rationale for pairing antiangiogenic activity with checkpoint inhibition upfront in non–small cell lung cancer (NSCLC), rather than sequencing them. She noted that prior attempts to combine or sequence bevacizumab (Avastin) with checkpoint inhibitors yielded only modest signals, hampered by bevacizumab’s long half-life and class-specific toxicities including bleeding risk that historically excluded patients with squamous cell carcinoma. By contrast, PD-L1/VEGF bispecifics such as pumitamig carry a significantly shorter half-life of approximately 5 to 6 days, resulting in a similar toxicity category but with lower rates of high-grade events and a broadened eligible population.
She highlighted the mechanistic rationale for this combination, explaining that VEGF and PD-L1 co-targeting appears to remodel the tumor microenvironment cooperatively, bringing cancer cells into closer proximity with T cells. In the case of PD-L1/VEGF bispecifics, a macromolecular structure forms in the tumor microenvironment that leads to internalization of PD-L1, creating a dual blockade of the PD-1/PD-L1 pathway beyond simple receptor occupancy.
Dr Peters then discussed data presented at the 2026 ASCO Annual Meeting from the phase 2/3 ROSETTA Lung-02 trial (NCT06712316) evaluating pumitamig plus chemotherapy in the first-line setting. She described the activity observed across all PD-L1 expression strata, including in PD-L1–negative patients, who comprised up to 70% of the nonsquamous population and achieved response rates above 50% as particularly compelling. She also addressed the dose selection rationale, noting that the 1500-mg dose demonstrated the optimal pharmacodynamic activity and favorable risk-benefit profile for phase 3 advancement.
Finally, Dr Peters offered broader perspective on the increasingly competitive PD-L1/VEGF bispecific landscape, including the parallel development of ivonescimab. She suggested that differences in clinical trial design including patient population, inclusion and exclusion criteria, and end point ambition may ultimately differentiate agents more than mechanism alone, and emphasized that global data will be essential to shaping regulatory and clinical practice decisions.

In today’s episode, we spoke with Tanios S. Bekaii-Saab, MD. Dr Bekaii-Saab is the David F. and Margaret T. Grohne Professor of Novel Therapeutics for Cancer Research I, at the Mayo Clinic College of Medicine and Science, the division chair of Hematology/Medical Oncology at Mayo Clinic, and co-leader of the Advanced Clinical and Translational Science Program and the disease group leader for Gastrointestinal Cancers for the Mayo Clinic Comprehensive Cancer Center in Phoenix, Arizona.
In our exclusive interview, Dr Bekaii-Saab discussed findings from the final analysis of cohort 3 of the phase 3 BREAKWATER trial (NCT04607421), which were presented at the 2026 ASCO Annual Meeting. These data showed that encorafenib (Braftovi) plus cetuximab (Erbitux) and FOLFIRI (leucovorin, 5-fluorouracil, and irinotecan) significantly improved outcomes compared with standard of care in patients with BRAF V600E–mutant metastatic colorectal cancer (mCRC), building on previously reported data from the trial that led to the February 2026 full FDA approval of encorafenib plus cetuximab and modified FOLFOX6 (leucovorin calcium, fluorouracil, and oxaliplatin) for this patient population. He also highlighted promising bispecific agents targeting VEGF and PD-1, as well as the promise of KRAS G12C inhibitors like calderasib (MK-1084) and sotorasib (Lumakras). Finally, he emphasized that minimal residual disease testing is prognostic and potentially predictive, and can aid in personalized mCRC management.

In today’s episode, we spoke with John N. Allan, MD. Dr Allan is an associate attending physician at New York-Presbyterian Hospital and an associate professor of clinical medicine at Weill Cornell Medical College in New York, New York. 
In our exclusive interview, Dr Allan discussed his review of the currently approved fixed-duration regimens for chronic lymphocytic leukemia (CLL). Regimens like venetoclax (Venclexta) plus obinutuzumab (Gazyva), ibrutinib (Imbruvica) plus venetoclax, acalabrutinib (Calquence) plus venetoclax, and venetoclax plus rituximab (Rituxan) were all regimens that Allan comparatively delved into. Additionally, Allan discussed insight provided by the review that clinical trials lack, remaining gaps of unmet needs for fixed-duration regimens in CLL, and what research is necessary for the field to conduct moving forward.

In today’s episode, we spoke with Marlana M. Orloff, MD. Dr Orloff is the Alexander & Johnston Family Endowed Clinical Director in Uveal Melanoma, and associate professor at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. 
In our exclusive interview, Dr Orloff discussed the distinct biology of uveal melanoma and why it has historically resisted systemic treatment. Unlike cutaneous melanoma, which carries a high tumor mutational burden and responds robustly to immune checkpoint inhibitors, uveal melanoma sits at the opposite end of the spectrum with low mutational burden, a predominantly liver-metastatic pattern, and an immune-tolerant microenvironment that renders traditional immunotherapy largely ineffective.
She provided context on the treatment landscape for patients with HLA-A*02:01–negative metastatic uveal melanoma prior to the phase 2/3 OptimUM-02 trial (NCT05987332), noting that this population had limited options: liver-directed therapies such as percutaneous hepatic perfusion, off-label immune checkpoint inhibitor combinations, or clinical trial enrollment.
Dr Orloff then walked through the design and efficacy findings of the trial, which evaluated the combination of darovasertib, an oral PKC inhibitor, plus crizotinib (Xalkori), a MET inhibitor, vs investigator’s choice in treatment-naive, HLA-A*02:01–negative patients. The combination demonstrated a median progression-free survival of 6.9 months vs 3.1 months with investigator’s choice, with an objective response rate of 37.1% compared with under 5.8% in the control arm. She highlighted the clinical significance of the complete responses observed while noting that overall survival data from the phase 3 portion of the trial remain pending.
The discussion also addressed the growing complexity of treatment sequencing as more options emerge, including tebentafusp-tebn (Kimmtrak) for HLA-A*02:01–positive patients, liver-directed and combination approaches, and the investigational TCR-engineered T-cell therapy anzutresgene autoleucel targeting PRAME. Dr Orloff emphasized that in the absence of head-to-head comparisons, sequencing decisions will increasingly be shaped by patient logistics, toxicity profiles, and access to specialized treatment centers.