FDA Gives Sacituzumab Govitecan the Green Light in Small Cell Lung Cancer

A Notable New Player in Second-Line Treatment

The US Food and Drug Administration (FDA), for patients with extensive-stage small cell lung cancer (ES-SCLC) whose disease progressed after platinum-based chemotherapy, granted sacituzumab govitecan-hziy (Trodelvy) Breakthrough Therapy designation. This decision was based on important tumor response and safety findings from the phase 2 TROPiCS-03 study presented at the 2024 World Conference on Lung Cancer.

Breakthrough Therapy is a special FDA designation given to treatments for serious or life-threatening diseases that offer the potential for substantial improvement over existing therapies. This designation expedites treatment review and approval, allowing earlier patient access.

Timeline of FDA Approvals for Trodelvy

• 3 February 2023: Sacituzumab Govitecan Receives FDA Approval for Hormone-Positive, HER2-Negative Advanced Breast Cancer 
• 13 April 2021: Sacituzumab Govitecan Receives FDA Approval for Advanced Urothelial (Bladder–Urinary Tract) Cancer 
• 22 April 2020: Sacituzumab Govitecan-hziy Receives FDA Approval for Advanced Triple-Negative Breast Cancer Treatment 

Results of the Phase 2 TROPiCS-03 Study

Updated data presented at the 2024 World Conference on Lung Cancer showed that sacituzumab govitecan had antitumor activity in ES-SCLC patients with and without platinum resistance.

• Data Cutoff Date: 8 March 2024

• Median Follow-Up: 12.3 months (range: 8.1-20.1 months)

This was a single-arm study with no control arm.

Clinical Response Rates

The clinical response rates observed in patients treated with sacituzumab govitecan were notable:

• Overall Response Rate: 41.9% (confidence interval [CI]: 27.0% to 57.9%).

• Disease Control Rate: 83.7% (CI: 69.3% to 93.2%).

• Clinical Benefit Rate: 48.8% (CI: 33.3% to 64.5%).

• Median Duration of Response (DOR): 4.7 months (CI: 3.5-6.7 months). All responding patients had a partial response, and 48.2% (CI: 23.9% to 68.9%) maintained this response at month 6.

• Median Time to Response: 1.4 months (range: 1.2-4.2 months).

These data support the clinical efficacy of sacituzumab govitecan, and phase 3 clinical trials are planned.

TROPiCS-03 Study Design

TROPiCS-03 is a phase 2 study involving patients with metastatic or locally advanced solid tumors.

Patients in the ES-SCLC cohort had to meet the following criteria:

• Diagnosis: Histologically confirmed extensive-stage small cell lung cancer (according to RECIST 1.1 criteria)

• Performance Status: ECOG PS 0 or 1

• Treatment History: Must have received 1 or fewer prior platinum-based chemotherapy and immunotherapy treatments.

Patients with stable brain metastases were also included in the study.

Treatment Regimen

• Sacituzumab Govitecan Dose: 10 mg/kg

• Administration: Intravenous injection on days 1 and 8 of 21-day cycles

Patient Profile:

• Median Age: 67 (range: 48-83)

• Smoking History: 97.7% (current or former smokers)

• ECOG PS 1: 81.4%

• Liver Metastases: 30.2%

• Brain Metastases: 11.6%

While 55.8% of patients had achieved a complete or partial response to previous treatments, 37.2% had stable or progressive disease.

Safety Data and Adverse Events

The adverse event profile of sacituzumab govitecan was consistent with data from its previously approved indications:

• Proportion of Patients with Treatment-Related Adverse Events: 100%

• Rate of Grade 3 or Higher Adverse Events: 74.4%

Most Common Adverse Events:

• Diarrhea: 67% (grade ≥3: 9%)

• Fatigue: 58% (grade ≥3: 2%)

• Neutropenia: 44%

• Constipation: 42%

• Nausea: 40%

• Alopecia: 30%

• Anemia: 26% (grade ≥3: 5%)

• Decreased appetite: 23%

• Abdominal pain: 19%

Serious adverse events occurred in 51.2% of patients, and dose reductions were required in 37.2%. There were 3 fatal adverse events, one of which was reported as directly drug-related.

Other Indications and Future Potential of Sacituzumab Govitecan

Sacituzumab govitecan is a TROP-2-directed antibody–drug conjugate currently approved in more than 50 countries for metastatic triple-negative breast cancer (TNBC). In the USA, it is used for various indications, including locally advanced or metastatic TNBC and hormone receptor-positive, HER2-negative breast cancer.

Various clinical trials are also ongoing to evaluate sacituzumab govitecan against tumors with high TROP-2 expression. Promising results have been obtained in the phase 2 EVOKE-02 study in patients receiving first-line treatment for metastatic non-small cell lung cancer (NSCLC), and in head and neck cancers and gynecological malignancies.

Conclusion

The clinical success of sacituzumab govitecan in ES-SCLC patients could open the door to a new treatment paradigm in small cell lung cancer. Completion of phase 3 studies will be crucial in defining this drug's future role.