Second-Line Sacituzumab Govitecan Elicits Responses, Provides Disease Control in ES-SCLC

Second-line treatment with sacituzumab govitecan-hziy (Trodelvy) led to responses in patients with extensive-stage small cell lung cancer (ES-SCLC), according to results from the phase 2 TROPiCS-03 trial (NCT03964727) presented at the 2023 ESMO Congress.¹

At a median follow-up of 5.1 months (range, 1.9-12.2), evaluable patients treated in the ES-SCLC cohort (n = 30) achieved an overall response rate (ORR) of 37% (95% CI, 20%-56%). All responders experienced a confirmed partial response, and the rates of stable disease and progressive disease were 50% and 10%, respectively. The disease control rate (DCR) with the antibody-drug conjugate was 87% (95% CI, 69%-96%) and the clinical benefit rate was 40% (95% CI, 23%-59%). Furthermore, the median duration of response (DOR) was 6.3 months (95% CI, 2.7-not reached), and the 6-month DOR rate was 63% (95% CI, 14%-89%).

“Seventy-seven percent of patients [who underwent] post-baseline tumor assessment [experienced] some kind of tumor reduction, and 43% had a reduction of greater than 30%,” lead study author Afshin Dowlati, MD, said in a presentation of the data. “Very few patients had up-front [disease] progression on their first imaging.”

Dowlati is a professor in the Department of Medicine Division of Hematology and Oncology in the School of Medicine, associate director for clinical research, and a member of the Developmental Therapeutics Program at Case Comprehensive Cancer Center in Cleveland, Ohio. He is also the Lucile and Robert H. Gries Endowed Director of the Center for Cancer Drug Development at University Hospitals, director of the Thoracic Oncology Program at University Hospitals Seidman Cancer Center, and the leader of the Lung Cancer and Thoracic Scientific Team at University Hospitals, Cleveland Medical Center.

Sacituzumab govitecan previously received full approval from the FDA for the treatment of adult patients with unresectable locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer who have received endocrine-based therapy and at least 2 additional systemic therapies in the metastatic setting in February 2023,² and for patients with unresectable locally advanced or metastatic triple-negative breast cancer who have previously received 2 or more systemic therapies, at least 1 of them for metastatic disease in April 2021.³

The regulatory agency also granted accelerated approval to the ADC for the treatment of patients with locally advanced or metastatic urothelial cancer who previously received a platinum-containing chemotherapy and either PD-1 or PD-L1 inhibitor.⁴

The ongoing, open-label, multicohort TROPiCS-03 study is evaluating sacituzumab govitecan in patients with locally advanced or metastatic solid tumors, including ES-SCLC.¹

To enroll in the ES-SCLC cohort, patients are required to have histologically confirmed ES-SCLC that progressed after no more than 1 prior line of platinum-based chemotherapy and anti–PD-1 or –PD-L1 therapy. Other key inclusion criteria include having measurable disease per RECIST v1.1 criteria and an ECOG performance status of 0 or 1. Patients with active central nervous system metastases and/or carcinomatous meningitis are not permitted.

Investigators plan to enroll approximately 40 patients in the ES-SCLC cohort. Treatment consists of 10 mg/kg of intravenous sacituzumab govitecan on days 1 and 8 of each 21-day cycle until progressive disease or unacceptable toxicity.

Investigator-assessed ORR serves as the trial’s primary end point. Secondary end points include investigator-assessed DOR, CBR, and progression-free survival (PFS); ORR, DOR, CBR, and PFS per blinded independent central review assessment; overall survival; and safety.

In the 30 patients treated prior to the data cutoff date of July 27, 2023, the median age was 67 years (range, 48-79), and 60% of patients were female. Ninety percent of patients were White, and 97% were current or former smokers. The majority of patients had an ECOG performance status of 1 (87%) and stage IV disease at initial diagnosis (93%). Fifty percent of patients experienced a complete response or PR to their last prior anticancer therapy, and 33% had stable disease or progressive disease on their last prior therapy.

The median duration of treatment was 3.9 months (range, 0-11.8), and patients received a median of 6 cycles (range, 1-17) of therapy. At data cutoff, 63% of patients had discontinued treatment, with the majority of discontinuations attributed to disease progression.

Regarding safety, all patients experienced any-grade treatment-emergent adverse effects (TEAEs), and 93% had TEAEs deemed related to study treatment. Grade 3 or higher TEAEs occurred in 60% of patients, 50% of which were related to treatment. The rates of serious TEAEs and serious TEAEs related to treatment were 30% and 13%, respectively.

Twenty-seven percent patients experienced TEAEs that led to dose reductions. However, TEAEs did not lead to treatment discontinuation or death in any patients.

The most common TEAEs reported in at least 15% of patients included diarrhea (grade 1/2, 66%; grade ≥3, 7%), neutropenia (14%; 33%), constipation (43%; 0%), fatigue (40%; 3%); nausea (43%; 0%), alopecia (27%; 0%), anemia (23%; 0%), decreased appetite (20%; 0%), vomiting (20%; 0%), abdominal pain (17%; 0%), and hypomagnesemia (17%; 0%).

“These results are encouraging in [patients with] ES-SCLC. The trial is ongoing, and we will hopefully have full results early [in 2024] with a full cohort. We believe that further investigation of [sacituzumab govitecan] in SCLC is warranted,” Dowlati concluded.

Editor’s note: Dr Dowlati reported serving in a consulting or advisory role for AstraZeneca, Ipsen, Jazz Pharmaceuticals, and Seattle Genetics. TROPiCS-03 was sponsored by Gilead Sciences.

References

1. Dowlati A, Cervantes A, Babu S, et al. Sacituzumab govitecan as second-line treatment for extensive stage small cell lung cancer. Ann Oncol. 2023;34(suppl 2):S1061-S1062. doi:10.1016/j.annonc.2023.09.1221
2. FDA approves sacituzumab govitecan-hziy for HR-positive breast cancer. FDA. February 3, 2023. Accessed October 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-sacituzumab-govitecan-hziy-hr-positive-breast-cancer
3. FDA grants regular approval to sacituzumab govitecan for triple-negative breast cancer. FDA. April 7, 2023. Accessed October 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-regular-approval-sacituzumab-govitecan-triple-negative-breast-cancer
4. FDA grants accelerated approval to sacituzumab govitecan for advanced urothelial cancer. FDA. April 13, 2021. Accessed October 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-sacituzumab-govitecan-advanced-urothelial-cancer