Trodelvy® (sacituzumab govitecan-hziy)

Combination With Pembrolizumab and Chemotherapy for 1L Treatment of Patients With mNSCLC

This document is in response to your request for information regarding the use of Trodelvy® (sacituzumab govitecan-hziy [SG]) in combination with pembrolizumab (pembro) and chemotherapy for first-line (1L) treatment in patients with metastatic non-small cell lung cancer (mNSCLC).

Some data may be outside of the US FDA-approved prescribing information. In providing this data, Gilead Sciences, Inc. is not making any representation as to its clinical relevance or to the use of any Gilead product(s). For information about the approved conditions of use of any Gilead drug product, please consult the FDA-approved prescribing information.

The full indication, important safety information, and boxed warnings for neutropenia and diarrhea are available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.

Summary

EVOKE-02 Study: SG + CP for 1L Treatment

EVOKE-02 is an ongoing, multi-cohort, phase 2 study evaluating the efficacy and safety of SG in combination with pembro ± PLT agent in the 1L treatment of adult patients with advanced or mNSCLC without AGAs.1

• During the safety run-in (SG 10 mg/kg + CP; n=5), the de-escalation criteria (≥2 patients with a predefined DLT) were not met. At a planned follow‑up safety evaluation, the SG dose was reduced to 7.5 mg/kg due to rates of myelosuppression (mainly Grade ≥3 neutropenia).
• In Cohort C (Sq; n=54), ORR was 45.1% (95% CI: 31.1–59.7%) and median PFS was 8.1 months (95% CI: 5.2–15%).
• In Cohort D (Sq; n=41), ORR was 39% (95% CI: 24.2–55.5%) and median PFS was 8.3 months (95% CI: 4.3–11.2%).
• The most common any-grade TEAEs in the SG 10 mg/kg + CP group were neutropenia (76%), anemia (75%), and diarrhea (69%).
• The most common any-grade TEAEs in the SG 7.5 mg/kg + CP group were anemia (65%), diarrhea (59%), and nausea (42%).

In an exploratory analysis with a later data cutoff date, Trop-2 expression ≥178 (median H‑score) was associated with a numerically higher PFS and ORR; however, the association was not statistically significant.2

EVOKE-02 Study: SG + CP for 1L Treatment

Study Design and Demographics

EVOKE-02 is an ongoing, open-label, multicenter, multi-cohort, phase 2 study (NCT05186974) evaluating the efficacy and safety of SG in combination with pembro ± PLT agent (eg, carbo) in the 1L treatment of adult patients with advanced or mNSCLC without AGAs (Figure 1).1

Figure 1. EVOKE-02: Study Design1,3

Abbreviations: DCR=disease control rate; G-CSF=granulocyte colony-stimulating factor; NSCLC=non-small cell lung cancer; RECIST=Response Evaluation Criteria in Solid Tumors.

aDe-escalating dose of SG (10 mg/kg, 7.5 mg/kg, and 5 mg/kg) IV on Days 1 and 8 + pembro 200 mg IV on Day 1 + carbo (AUC 5) IV on Day 1 of a 21-day cycle.

bBased on safety assessment, mandatory long-acting G-CSF on Day 9 or short-acting G-CSF once daily for 10 days starting from Day 9 of each cycle.

The baseline demographics and disease characteristics of patients included in a preliminary analysis of Cohorts C and D are shown in Table 1.

Table 1. EVOKE-02 (Cohorts C and D):
Select Baseline Demographics and Disease Characteristics1

Results: Cohort C and Cohort D1

Safety run-in

During the safety run-in (SG 10 mg/kg + CP; n=5), the de-escalation criteria (≥2 patients with a predefined DLT) were not met. One DLT of sepsis leading to death was seen. At a planned follow‑up safety evaluation, the SG dose was reduced to 7.5 mg/kg due to rates of myelosuppression (mainly Grade ≥3 neutropenia). The RP2D was 7.5 mg/kg of SG combined with pembro 200 mg and carbo AUC 5.

Preliminary efficacy

In Cohort C, 17 patients (31%) received SG 10 mg/kg + CP, and 37 patients (69%) received SG 7.5 mg/kg + CP. In Cohort D, 12 patients (29%) received SG 10 mg/kg + CP, and 29 patients (71%) received SG 7.5 mg/kg + CP. The median (range) durations of follow-up were 14.5 (12.2–22.3) and 14.2 (11–23) months for Cohorts C and D, respectively. Three patients in Cohort C did not have measurable disease per IRC at baseline and were not included in the efficacy analysis. Efficacy results overall and by PD-L1 expression for patients receiving SG 7.5 mg/kg or 10 mg/kg + CP are shown in Table 2 and Table 3, respectively.

Table 2. EVOKE-02 (Cohorts C and D): Efficacy by IRC1

aPatients received SG 7.5 mg/kg or 10 mg/kg.

Table 3. EVOKE-02 (Cohorts C and D): Efficacy by PD-L1 Expression1

aPatients received SG 7.5 mg/kg or 10 mg/kg.

For patients with tumors that had PD-L1 TPS ≥1% (n=48), ORR was 41.7% (95% CI: 27.6–‍56.8%) and median PFS was 8.4 (95% CI: 5.3–11.2%) months.

Preliminary safety

Any-grade TEAEs were reported in all patients in each SG dose group, and a safety summary by SG dose is shown in Table 4. Grade ≥3 TEAEs occurred in 93.1% of the SG 10 mg/kg + CP group and in 86.4% of the SG 7.5 mg/kg + CP group. Grade 1 to 2 TEAEs occurred in 7% of the SG 10 mg/kg + CP group and in 14% of the SG 7.5 mg/kg + CP group. Additional TEAEs seen in ≥25% of patients are shown in Table 5.

Table 4. EVOKE-02 (Cohorts C and D): Summary of TEAEs by Dose Received1

aIncluded sepsis (n=3), pneumonia (n=1), and abdominal infection (n=1) in the SG 10 mg/kg group and pneumonia (n=3), sepsis (n=2), febrile neutropenia (n=1), bacterial sepsis (n=1), gastroenteritis (n=1), pneumococcal sepsis (n=1), and hypoglycemia (n=1) in the SG 7.5 mg/kg group.

Table 5. EVOKE-02 (Cohorts C and D): TEAEs in ≥25% of Patients by Dose Received1

Subanalysis: Efficacy by Trop-2 Expression2

An exploratory analysis with a later data cutoff date evaluated efficacy outcomes according to Trop-2 expression. Trop-2 membrane expression on archival tumor tissue was assessed with immunohistochemistry and expressed as an H-score of 0 to 300. Trop-2 expression was assessed for association with ORR and PFS. Clinical outcomes were evaluated in 184 patients with evaluable archival tissue. With a median Trop-2 H‑score of 178, outcomes were assessed in H-score groups of <178 and ≥178. To boost the numbers for subgroup analyses, Trop-2 subgroups from Cohorts A + B + C + D were combined to correlate with evaluated efficacy outcomes.

In patients who received SG + CP, there was no correlation between Trop-2 expression and best percentage change in tumor size (Spearman correlation coefficient ρ=-0.01) or best overall response. Trop-2 expression ≥ median H-score resulted in numerically higher but not statistically significant PFS and ORR (Table 6).

Table 6. EVOKE-02 Subanalysis of Trop-2 Status: Efficacy2

References

1. Gray JE, Neal JW, Patel JD, et al. Sacituzumab govitecan + pembrolizumab + carboplatin in 1L metastatic non–small cell lung cancer: the EVOKE-02 study [Oral Presentation OA08.07]. Presented at: 2024 World Conference on Lung Cancer (WCLC); September 7-10, 2024; San Diego, CA.
2. Patel J, Zavodovskaya M, Chul Cho B, et al. Trop-2 expression and association with efficacy in patients treated with sacituzumab govitecan + pembrolizumab +/- carboplatin in the EVOKE-02 study of non-small cell lung cancer (Poster LB399). Presented at: American Association for Cancer Research (AACR); April 25-30, 2025; Chicago, IL, USA.
3. ClinicalTrials.gov. Study of sacituzumab govitecan combinations in first-line treatment of participants with advanced or metastatic non-small-cell lung cancer (NSCLC) (EVOKE-02). ClinicalTrials.gov Identifier: NCT05186974. Available at: https://www.clinicaltrials.gov/ct2/show/NCT05186974.

Abbreviations

1L=first-line
AGA=actionable genomic alteration
AUC=area under the concentration-time curve
carbo=carboplatin
BEP=biomarker-evaluable population
CP=carboplatin + pembrolizumab
DLT=dose-limiting toxicity
DOR=duration of response
H-score=histochemical-score

IRC=independent review committee
mNSCLC=metastatic non-small cell lung cancer
NE=not evaluable
NR=not reached
Nsq=nonsquamous
ORR=objective response rate
PD=progressive disease
PD-L1=programmed cell death-ligand 1
pembro=pembrolizumab
PFS=progression-free survival
PLT=platinum
PR=partial response
RP2D=recommended phase 2 dose
SD=stable disease
SG=sacituzumab govitecan-hziy
Sq=squamous
TEAE=treatment-emergent adverse event
TPS=tumor proportion score
Trop-2=trophoblast cell surface antigen-2

 

Product Label

For the full indication, important safety information, and boxed warning(s), please refer to the Trodelvy US Prescribing Information available at:
www.gilead.com/-/media/files/pdfs/medicines/oncology/trodelvy/trodelvy_pi.

Follow-Up

For any additional questions, please contact Trodelvy Medical Information at:

☎1‐888-983-4668 or   www.askgileadmedical.com

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Please report all adverse events to:

Gilead Global Patient Safety ☎ 1-800-445-3235, option 3 or
 www.gilead.com/utility/contact/report-an-adverse-event

FDA MedWatch Program by ☎ 1-800-FDA-1088 or MedWatch, FDA, 5600 Fishers Ln, Rockville, MD 20852 or   www.accessdata.fda.gov/scripts/medwatch

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