Sacituzumab Govitecan Demonstrates Modest Activity in Pretreated HNSCC

Loren Scott Michel, MD

Sacituzumab govitecan-hziy (Trodelvy) led to modest but durable antitumor activity with predominant gastrointestinal toxicities in patients with metastatic or locally recurrent head and neck squamous cell carcinoma (HNSCC) who received between 1 and 3 prior lines of therapy, according to findings from the phase 2 TROPiCS-03 trial (NCT03964727) that were presented at the 2023 ESMO Congress.

At a median follow-up of 7.8 months (range, 0.6-19.8), the investigator-assessed objective response rate (ORR) was 16% (95% CI, 7%-31%) in this patient population (n = 43). Best objective responses included confirmed partial response (16%), stable disease (49%), and progressive disease (21%). The clinical benefit rate (CBR) was 28% (95% CI, 15%-44%), and the median duration of response (DOR) was 4.2 months (95% CI, 2.6-not reached). At 6 months, 43% (95% CI, 10%-73%) of patients remained in response. The median progression-free survival (PFS) was 4.1 months (95% CI, 2.6-5.8).

“Sacituzumab govitecan demonstrated single-agent antitumor activity in heavily pretreated patients with metastatic or locally advanced recurrent HNSCC,” lead study author Loren Scott Michel, MD, associate attending physician and head and neck oncologist at Memorial Sloan Kettering Cancer Center in New York, New York, said in a presentation of the data. “These preliminary results warrant further investigation of sacituzumab govitecan for the treatment of [patients with] HNSCC.”

Patients with advanced HNSCC may derive benefit from PD-(L)1 inhibitors but most will develop disease progression. Sacituzumab govitecan is a Trop-2–directed antibody-drug conjugate currently indicated for patients with metastatic triple-negative breast cancer who have received at least 1 prior line of therapy; patients with hormone receptor–positive, HER2-negative metastatic breast cancer; and patients with pretreated metastatic urothelial cancer.

Given the high expression of Trop-2 in HNSCC, investigators sought to evaluate sacituzumab govitecan in patients with locally recurrent and metastatic disease.

TROPiCS-03 is an ongoing, open-label, multicohort, phase 2 study evaluating sacituzumab govitecan in patients with metastatic or locally advanced recurrent solid tumors. To be eligible for enrollment, patients had to have histologically confirmed metastatic or locally recurrent HNSCC, disease progression after prior platinum-based chemotherapy and anti–PD-(L)1 therapy, measurable disease per RECIST v1.1 criteria, and an ECOG performance status of 0 or 1.

Participants received 10 mg/kg of intravenous sacituzumab govitecan on day 1 and 8 of every 21-day cycle until progressive disease or unacceptable toxicity.

Investigator-assessed ORR served as the primary end point. Secondary end points included DOR, CBR, and PFS by investigator assessment and blinded independent review committee assessment as well as overall survival and safety.

Regarding baseline characteristics, the median patient age was 62 years (range, 46-75). Most patients were male (77%), White (77%), current or former smokers (74%), and human papillomavirus negative (51%). Additionally, most patients had metastatic disease (86%) and experienced stable disease or progressive disease (86%) as their best response to their last line of prior therapy. Patients received 1 (33%), 2 (35%), or more than 2 (33%) prior lines of therapy in the incurable setting and all had received prior chemotherapy and immunotherapy. Only 51% of patients received prior targeted therapy. Primary sites of disease included the nasopharynx (2%), oropharynx (44%), larynx (26%), nasal (5%), and oral (19%) cavities.

The median duration of treatment was 2.5 months (range, 0.3-12.3) and the median number of cycles received was 4 (range, 1-17). The most common reason for treatment discontinuation was progressive disease.

Additional efficacy findings revealed that 51% of patients with post-baseline tumor assessment experienced any level of tumor reduction and 16% of patients experienced more than a 30% reduction in tumor size.

All patients were evaluable for safety. Any-grade treatment-emergent adverse effects (TEAEs) related to study treatment occurred in all patients. Overall grade 3 or higher TEAEs and those related to study treatment occurred in 58% and 44% of patients, respectively. Serious TEAEs and those related to study treatment occurred in 30% and 12% of patients, respectively. Twenty-one percent of patients experienced TEAEs that led to dose reduction.

Three deaths occurred due to TEAEs, 1 of which was related to study treatment.

The most common TEAEs that occurred in at least 15% of patients were diarrhea (grade 1/2, 45%; grade ≥3, 2%), nausea (40%; 7%), neutropenia (14%; 33%), fatigue (42%; 2%), alopecia (37%; 0%), vomiting (31%; 2%), anemia (21%; 9%), dyspnea (19%; 7%), decreased appetite (21%; 2%), leukopenia (10%; 9%), and hyponatremia (14%; 2%).

“The safety profile of sacituzumab govitecan was manageable and consistent with its known safety profile, and treatment-emergent adverse effects leading to treatment discontinuation were low, at 5%,” Michel concluded.

Editor's Note: Dr Michel disclosed a consulting agreement with Kisoji Biotechnology and study sponsorship from Gilead Sciences, Inc.

Clinicians referring a patient to MSK can do so by visiting msk.org/refer, emailing referapatient@mskcc.org, or by calling 833-315-2722.

Reference

Michel L, Jimeno A, Sukari A, et al. Sacituzumab govitecan (SG) in patients (pts) with relapsed/refractory (R/R) advanced head and neck squamous cell carcinoma (HNSCC): Results from the phase II TROPiCS-03 basket trial. Ann Oncol. 2023;34(suppl 2):S558. doi:10.1016/j.annonc.2023.09.2005