According to Robert L. Ferris, MD, PhD, there is a steady pace of drug development for head and neck cancers despite modest findings with durvalumab triplet.
Robert L. Ferris, MD, PhD
We continue to observe the steady pace of drug development, which employs rational combinations based on preclinical science and biology paired with promising small developmental trials. Fortunately, innovative agents are still able to emerge, allowing for progress through further clinical evaluation even when early trial results are equivocal. From the European Society for Medical Oncology (ESMO) Immuno-Oncology (IO) Congress 2021, 1 particular trial deserves mention as an exemplar. In head and neck squamous cell carcinoma (HNSCC) there has been a drought of recent positive trial data. Although further IO combinations with doublet immune checkpoint inhibitor combinations continue to be tested, a different strategy targeting natural killer (NK) cells has shown promise.
Findings from the phase 1/2 clinical trial IPH2201-203 (NCT02643550) showed a confi rmed objective response rate (ORR) of 32.5% for all patients, regardless of PD-L1 status, and the unconfi rmed ORR was 50% [page 31]. This result compares favorably with the CheckMate 651 trial (NCT02741570) or pembrolizumab (Keytruda) plus chemotherapy in the KEYNOTE-048 trial (NCT02358031). The combined positive score of PD-L1 greater than 1 was 63% vs 80% in other trials, so this was not necessarily a cohort that was highly immune responsive. A combination of cetuximab (Erbitux) and monalizumab that blocks an inhibitory receptor in NKG2A on NK cells had previously shown activity in recurrent or metastatic HNSCC and in a separate cohort of patients who were PD-1 refractory. Given these exciting early data, the cetuximab and monalizumab combination appears to be enhanced with the addition of durvalumab (Imfi nzi). Indeed, durvalumab is not approved for HNSCC despite indications of its activity in first- and second-line trials that were negative overall. Durvalumab had “failed” in prior HNSCC phase 3 trials, though a glimmer of activity was observed. This example of developing new immunobiology translating to the clinic is innovative because it does not simply rely on a new T-cell targeted immunotherapy but rather on harnessed NK cells, long felt to be key antitumor immune effectors and helper cell.
Buttressed by the promising data from those trials of development of activity in HNSCC, AstraZeneca saw enough activity to remain enthusiastic about prospects for durvalumab, used here as a triplet IO regimen. This is a model for the fi eld to progress multiple antibody combinations and possibly re-introduce specifi c agents which had not succeeded alone in other trials but may leverage other target assets using rational biological combinations.
Leon-Ferre Explores Targeting of PIK3CA Alterations in ER+ Breast Cancer
July 24th 2024During a live Community Case Forum event in partnership with the Minnesota Society of Clinical Oncology, Roberto A. Leon-Ferre, MD, discussed drugs targeting PIK3CA alterations in patients with ER+ metastatic breast cancer.
Read More
Roundtable Roundup: Treatment for Metastatic pMMR Endometrial Cancer
July 23rd 2024In separate, live virtual events, Michael J. Birrer, MD, PhD, and Jubilee Brown, MD, surveyed participants on the treatment of a postmenopausal woman with stage IVA endometrial cancer after first-line chemotherapy.
Read More
George Explores Impact of Risk Status With Cabozantinib/Nivolumab in Advanced RCC
July 19th 2024During a Case-Based Roundtable® event, Daniel George, MD, discussed the results of the CheckMate 9ER trial across favorable, intermediate, and poor risk groups in patients with advanced renal cell carcinoma.
Read More
Depth of Response With Quadruplet Regimens Considered in Newly Diagnosed Multiple Myeloma
July 18th 2024During a Case-Based Roundtable® event, Timothy Schmidt, MD, and participants discussed treatment selection for a 54-year-old patient with transplant eligible R-ISS stage 2/R2-ISS stage 3 IgG-κ myeloma.
Read More
Rossetti Reviews Myelofibrosis Risk Stratification and Outcome Data for Pacritinib
July 17th 2024During a Case-Based Roundtable® event, James M. Rossetti, DO, discussed the role of risk scoring and stratification tools and treatment for a patient with declining hemoglobin and platelet counts due to primary myelofibrosis.
Read More