Memorial Sloan Kettering Cancer Center | Strategic Alliance Partners

Twelve years after key research into immune checkpoint inhibitor therapy first made a splash at the American Society of Clinical Oncology Annual Meeting, evidence continues to mount that supports the durability of these agents in a range of cancers.

An influx of bispecific T-cell engagers, CAR T-cell therapies, and antibody-drug conjugates have revolutionized the treatment of hematologic malignancies; however, with several options in the sandbox, accessibility and unexplored clinical questions present challenges for optimal integration of these options into treatment.

Neratinib-based combinations, antibody-drug conjugates, and bispecific antibodies represent novel and effective treatment options for patients with pretreated HER2-mutant and HER2-low metastatic breast cancer, but the successful integration of these regimens into care will require further investigation into current definitions of HER2 positivity.

Raajit K. Rampal, MD, PhD, discusses the potential utilization of navtemadlin in relapsed/refractory acute myeloid leukemia and patients with blast phase myeloproliferative neoplasm in a phase 1b/2 trial.

Batiraxcept will continue to be investigated in combination with cabozantinib, plus in combination with cabozantinib and nivolumab and as a single agent, in patients with advanced or metastatic clear cell renal cell carcinoma in a phase 2 study.

The European Medicines Agency has validated a Type II Variation application for trastuzumab deruxtecan as monotherapy for adults with unresectable or metastatic HER2-low breast cancer.

A single infusion of the CAR T-cell therapy ciltacabtagene autoleucel produced deep and durable responses in patients with relapsed/refractory multiple myeloma with a manageable toxicity profile, according to long-term follow-up data of the phase 1b/2 CARTITUDE-1 trial.

Fam-trastuzumab deruxtecan-nxki demonstrated a statistically significant benefit in progression-free survival in patients with HER2-low metastatic breast cancer, meeting the primary end point of the phase 3 DESTINY-Breast04 trial and changing the standard of care for this patient population.

Dr Lee highlights treatment developments in non–clear cell renal cell carcinoma, emphasizes the need for precise classification of the histologic subsets of this disease, and discusses the investigation of cabozantinib plus nivolumab across stratified cohorts of non–clear cell renal cell carcinoma.

Eytan M. Stein, MD, discusses the phase 2 SELECT-AML-1 trial in patients with newly diagnosed acute myeloid leukemia.

Eytan M. Stein, MD, discusses the phase 1/2 KOMET-001 trial in relapsed/refractory acute myeloid leukemia.

Single-agent dostarlimab-gxly elicited a clinical complete response rate of 100% with no evidence of residual tumor among 14 patients with stage II/III mismatch repair–deficient locally advanced rectal cancer.

Tiragolumab combined with atezolizumab plus carboplatin and etoposide demonstrated no additional survival benefits compared with atezolizumab plus chemotherapy alone in patients with treatment-naïve, extensive-stage small cell lung cancer.

Treatment with larotrectinib elicited robust and durable responses, had a favorable safety profile, and sustained survival benefit in patients with central nervous system TRK fusion cancers.

Zenocutuzumab was found to produce durable responses in patients with previously treated advanced NRG1-positive cancers, with antitumor activity observed across several tumor types, and to have an extremely well tolerated toxicity profile, according to data from a phase 1/2 trial (NCT02912949).

Treatment with fam-trastuzumab deruxtecan-nxki doubled progression-free survival and reduced the risk of death by 36% compared with physician's choice of chemotherapy for patients with HER2-low, hormone receptor–positive metastatic breast cancer.

The combination of lenvatinib and pembrolizumab demonstrated clinically meaningful improvements in progression-free survival on next line of therapy among all-comer patients with advanced endometrial cancer and those with DNA mismatch repair proficient disease, according to an exploratory analysis of the phase 3 KEYNOTE-775 trial.

The addition of subcutaneous epcoritamab to treatment with rituximab and lenalidomide resulted in a 100% response rate and a low incidence of low-grade cytokine release syndrome in patients with relapsed/refractory follicular lymphoma, according to findings from arm 2 of the EPCORE NHL-2 trial.

The addition of subcutaneous epcoritamab to standard-of-care R-CHOP demonstrated clinically meaningful response in the first-line treatment of patients with high-risk diffuse large B-cell lymphoma according to updated results of a single-arm of the EPCORE NHL-2 trial.

The selective EGFR inhibitor CLN-081 elicited objective responses in heavily pretreated patients with non–small cell lung cancer with EGFR exon 20 insertions and was found to have an acceptable toxicity profile, according to data from the phase 1/2a CLN-081-001 trial.

The combination of the humanized anti-GD2 antibody naxitamab-gqgk, irinotecan, temozolomide, and sargramostim met its primary end point for objective response rate in patients with chemoresistant high-risk neuroblastoma.

Chung-Han Lee, MD, PhD, explains the historical barriers to treatment developments in non-clear cell renal cell carcinoma; highlights the efficacy of cabozantinib plus nivolumab in patients with unclassified, translocation, papillary, and fumarate hydratase–deficient non-clear cell renal cell carcinoma; and elaborates on the need for increased molecular classification of the histologic subsets of non-clear cell renal cell carcinoma.

Selinexor monotherapy prolonged progression-free survival, time to next treatment, and reduced pain in patients with advanced, refractory dedifferentiated liposarcoma.

The American Urologic Association in collaboration with the American Society for Radiation Oncology has issued new practice guidelines for the management of clinically localized prostate cancer.

The combination of cabozantinib plus nivolumab demonstrated promising objective response rates in patients with non–clear cell renal cell carcinoma with prominent papillary features.

Anthony Mato, MD, MSCE, discusses current data surrounding BTK inhibitors in chronic lymphocytic leukemia, the benefits of targeted therapies in this population, ways to begin addressing unmet needs, and the importance of improved clinical trial designs for varying patient populations.

Steven Maron, MD, MSc, discusses sequencing considerations in the frontline treatment of gastrointestinal cancers.

Steven Maron, MD, MSc, discusses HER2-positive tumors in esophageal gastric cancers.

Checkpoint inhibitors prior to allogeneic hematopoietic cell transplant improved progression-free survival and relapse incidence in patients with Hodgkin lymphoma, but the treatment did not improve non-relapse mortality or overall survival.

“I can’t conceive of anything worse than being in a situation where you can’t ask, ‘How do we get better?’ ”