In this episode of Oncology Unplugged, host Chandler Park, MD, a medical oncologist at Norton Cancer Institute in Louisville, Kentucky, was joined by Pashtoon Kasi, MD, MS, the medical director of GI Medical Oncology, the Rad Family Chair in Gastrointestinal Oncology, and an associate clinical professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Orange County in Irvine, California.

Their discussion centered on the rapid rise of neoadjuvant immunotherapy in colorectal cancer (CRC) management, framing the shift in which immunotherapy is given upfront and surgery becomes the adjuvant step as a genuine paradigm change. Drs Park and Kasi grounded the conversation in the biology of mismatch repair–deficient (dMMR)/microsatellite instability–high tumors, which harbor a high neoantigen load, rendering them sensitive to checkpoint blockade.

A major focus was the treatment evolution that stemmed from data from the phase 3 ATOMIC trial (NCT02912559), which added atezolizumab (Tecentriq) to FOLFOX (leucovorin, fluorouracil, oxaliplatin) in stage III dMMR disease, to the NICHE clinical trial series from the Netherlands, in which brief neoadjuvant nivolumab (Opdivo) plus 1 dose of ipilimumab (Yervoy) produced near-universal responses. Dr Kasi then detailed his own NEST trials, which replicated this short-course design using the Fc-enhanced CTLA-4 inhibitor botensilimab plus balstilimab, notably extending activity into the larger mismatch repair–proficient/microsatellite stable (MSS) population with sustained disease-free survival.

Drs Park and Kasi explored mechanistic insights that have been seen with CRC drugs, including an "inside-out" serosal-to-mucosal response pattern, regulatory T cell depletion, and the rationale that an intact tumor and lymph nodes provide more antigens than the postsurgical setting. They also discussed circulating tumor DNA as an emerging surrogate end point, the implications of data from the phase 3 STELLAR-303 trial (NCT05425940) of an immunomodulatory TKI plus atezolizumab (Tecentriq) in patients with MSS disease, liver metastases as an immunosuppressive niche, and the alarming rise of early-onset CRC.

In today’s episode, we spoke with Vincent Chung, MD, about the development of atebimetinib (IMM-1-104) in metastatic pancreatic cancer. Dr Chung is a professor in the Department of Medical Oncology & Therapeutics Research at City of Hope in Duarte, California.

In our exclusive interview, Dr Chung discussed MEK inhibition as a logical target in metastatic pancreatic cancer, the unique mechanism of action of atebimetinib that contributes to its improved tolerability relative to earlier-generation MEK inhibitors, key safety and efficacy findings from a phase 2a trial (NCT05585320) combining atebimetinib with modified gemcitabine/nab-paclitaxel (Abraxane) in patients with advanced or metastatic disease, and how the outcomes of the ongoing phase 3 MAPkeeper-301 trial may affect the treatment paradigm going forward.

In today’s episode, we spoke with Triparna Sen, PhD, and Jacob Sands, MD. Dr Sen is a professor of internal medicine and the director of the Lung Cancer Preclinical Therapeutics Platform at the Ohio State University Comprehensive Cancer Center—James in Columbus. Dr Sands is associate chief of the Lowe Center for Thoracic Oncology and the oncology medical director of the International Patient Center at Dana-Farber Cancer Institute, as well as an assistant professor at Harvard Medical School in Boston, Massachusetts.

In our exclusive interview, Drs Sen and Sands discussed findings from the phase 3 IMforte trial (NCT05091567), which showed that adding lurbinectedin (Zepzelca) to atezolizumab (Tecentriq) maintenance following carboplatin, etoposide, and atezolizumab induction improved outcomes in patients with extensive-stage small cell lung cancer (SCLC). Dr Sen noted that although the regimen’s safety profile was manageable, the combination does increase rate of hematologic toxicities, including anemia, neutropenia, and thrombocytopenia, so the key question is whether the added treatment burden is justified by longer disease control and survival. Dr Sands added that the neutropenia rates in IMforte were lower than in the earlier second-line lurbinectedin experience, likely because primary prophylaxis, such as granulocyte colony-stimulating factor, was permitted.

The experts also weighed in on a trial in progress presented at the 2026 World Conference on Lung Cancer evaluating lurbinectedin plus durvalumab (Imfinzi) as maintenance therapy. Dr Sen explained that a positive result could show that the strategy is reproducible with a different PD-L1 inhibitor and induction regimen but cautioned against assuming a class-wide effect or treating the 2 regimens as interchangeable. Dr Sands said he would not expect durvalumab to perform differently from atezolizumab in this context, and that the more pressing question is whether lurbinectedin belongs in maintenance at all, particularly as the IMforte curves have converged with longer follow-up. Both experts pointed to the phase 3 DeLLphi-305 trial (NCT06211036) of tarlatamab (Imdelltra) plus durvalumab vs durvalumab alone as first-line maintenance, which has reported positive OS and PFS results via press release, as the most significant development to watch in this space.

Turning to the relapsed setting, Drs Sen and Sands discussed the negative phase 3 LAGOON trial (NCT05153239), in which neither lurbinectedin monotherapy nor lurbinectedin plus irinotecan improved OS vs investigator’s choice of topotecan (Hycamtin) or irinotecan, leading to the withdrawal of lurbinectedin’s second-line indication. Dr Sands highlighted that the control arm median OS was unexpected given the median OS data that supported the original accelerated approval of the agent. Both experts emphasized that the LAGOON results should not be conflated with the maintenance data, and Dr Sands expressed hope that lurbinectedin remains a guideline-listed option in later lines, citing its convenient every-3-week dosing.

Finally, the experts looked ahead to emerging therapies. Dr Sands discussed B7-H3–directed antibody-drug conjugates (ADCs), including YL201 and ifinatamab deruxtecan. He also outlined practical toxicity management for ADCs, including cytopenias, nausea, fatigue, alopecia counseling, and the challenge of distinguishing drug-related interstitial lung disease from waxing and waning inflammatory findings common in SCLC. Dr Sen highlighted anticipated data at the 2026 ESMO Congress and stressed that treatment selection in SCLC maintenance will depend on magnitude of benefit, patient selection, toxicity, and center capabilities rather than a one-size-fits-all approach.