Trodelvy® (sacituzumab govitecan-hziy)

Use in Combination With Pembrolizumab in Patients With 1L PD-L1+ mTNBC

This document is in response to your request for information regarding Trodelvy® (sacituzumab govitecan [SG]) and its use in combination with pembrolizumab (pembro) as first-line (1L) treatment in patients with programmed death ligand-1 positive (PD-L1+) metastatic triple-negative breast cancer (mTNBC).

Trodelvy is not indicated for use in patients with 1L PD-L1+ mTNBC. 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

Clinical Data on SG Use in Combination With Pembro in 1L PD-L1+ mTNBC1

ASCENT-04, an ongoing, global, open label, randomized, phase 3 study compared the efficacy and safety of SG + pembro vs chemotherapy TPC (gemcitabine + carboplatin, paclitaxel, or nab-paclitaxel) + pembro, as 1L treatment in patients with PD-L1+ (CPS ≥10), inoperable, locally advanced or mTNBC (Figure 1). A total of 443 female patients were enrolled. Patients who experienced disease progression during treatment with TPC + pembro (as verified by BICR) could crossover to receive 2L SG monotherapy.

• SG + pembro prolonged PFS by BICR per RECIST v1.1 (primary endpoint) vs TPC + pembro (11.2 vs 7.8 mo; HR 0.65 [95% CI 0.51–0.84] P<0.001).
  • A higher proportion of patients treated with SG + pembro vs TPC + pembro, respectively, were alive and progression-free at 6 mo, 72% (95% CI 65–77) vs 63% (95% CI 56–69), and at 12 mo, 48% (95% CI 41–56) vs 33% (95% CI 26–40).
  • Median follow-up at the time of the final PFS analysis was 14 (range, 0.1–28.6) mo.
• Results for OS were immature (26% maturity rate) at the time of the final PFS analysis, therefore, results are descriptive; a numerical trend in favor of SG + pembro was observed; HR 0.89 (95% CI 0.62–1.29). Further follow-up for OS is ongoing.

• An ORR of 60% was observed in patients receiving SG + pembro vs 53% for TPC + pembro (OR 1.3; 95% CI 0.9–1.9). DOR (95% CI) with SG + pembro vs TPC + pembro was 16.5 (12.7–19.5) mo vs 9.2 (7.6–11.3) mo, respectively. Formal statistical analyses of these results were not conducted at this time.

• A total of 77 patients who progressed on TPC + pembro within the study crossed over to receive 2L SG monotherapy per protocol.
• The safety profile of SG + pembro was consistent with the known safety profile of each agent. No new safety concerns emerged with the combination.
  • The most common any-grade TEAEs were diarrhea (70 vs 29%), nausea (68 vs 38%), and neutropenia (63 vs 59%) with SG + pembro vs TPC + pembro, respectively.
  • In the SG + pembro vs TPC + pembro groups, respectively, treatment-emergent SAEs were 38 vs 31%, of these, treatment-related SAEs were 28 vs 19%.
  • Incidence of TEAEs that led to treatment discontinuation were 12% with SG + pembro and 31% with TPC + pembro.
  • Rates of TEAEs that led to death were 3% in both treatment arms; 1% and <1% were deemed treatment-related with SG + pembro and TPC + pembro, respectively.

Clinical Data on SG Use Combination With Pembro in 1L PD-L1+ mTNBC

ASCENT-04 Study

Study design and demographics

ASCENT-04 is an ongoing, global, open label, randomized, phase 3 study that is being conducted to investigate the efficacy and safety of SG + pembro vs TPC + pembro, as 1L treatment in patients with PD-L1+ (CPS ≥10), inoperable, locally advanced or mTNBC (Figure 1).1

A total of 443 female patients were enrolled. Patients who experienced disease progression during treatment with TPC + pembro (as verified by BICR) could crossover to receive 2L SG monotherapy.1

Figure 1. ASCENT-04 Study Design1,2

aHemoglobin ≥9 g/dL, ANC ≥1500/mm3; platelets ≥100,000/μL, bilirubin ≤1.5 × ULN, AST/ALT ≤2.5 × ULN or
≤5 × ULN with known liver metastases, serum albumin >3 g/dL, and CrCl ≥30 mL/min.

bUnresolved Grade ≤2 neuropathy, endocrine-related AEs, and any-grade alopecia were allowed.

cUp to 35% of patients with de novo mTNBC were eligible.

Table 1. ASCENT-04: Baseline Demographics and Disease Characteristics1

Abbreviation: ECOG PS: Eastern Cooperative Oncology Group performance status.

aAs reported by patients; other includes American Indian or Alaska Native, and not permitted.

bIncludes Argentina, Australia, Brazil, Chile, Czech Republic, Hong Kong, Hungary, Israel, Japan, Malaysia, Mexico, Poland, Singapore, South Africa, South Korea, Taiwan, and Turkey.

cOne patient in the TPC + pembro group had an ECOG PS ≥2.

dOther metastatic sites includes pleura, pleural effusion, skin, soft tissue, chest wall, and muscle.

eActual chemo received was consistent with what was selected prior to randomization; however, two patients were randomized but did not receive treatment.

fWhile 20 patients were included in the stratified subgroup of prior exposure to anti-PD-(L)1 therapy (yes) per the interactive response technology system, only six patients received prior treatment with anti-PD-(L)1 agents per the clinical database.

Efficacy1

Primary endpoint

SG + pembro significantly improved PFS vs TPC + pembro with a 35% reduction in the risk of disease progression or death, and a higher proportion of patients alive and progression-free at the 6- and 12-month timepoints (Table 2). The median duration of follow-up at the time of the final PFS analysis was 14 (range, 0.1–28.6) mo. At data cutoff date, 43% (n=95) of patients in the SG + pembro arm and 23% (n=52) of patients in the chemo + pembro arm remained on study treatment.

Table 2. ASCENT-04: PFS by BICR and Investigator Assessment1

Secondary endpoints

At the data cut-off for the final PFS analysis, results for OS were immature (26% maturity

rate), results for OS are, therefore, descriptive; a numerical trend in favor of SG + pembro

was observed; HR 0.89 (95% CI 0.62–1.29).

A total of 77 patients who progressed on TPC + pembro crossed over to receive 2L

SG monotherapy per protocol.

Statistical testing was not conducted for subsequent endpoints in the statistical hierarchy as

the statistical boundary for OS was not crossed, results of these endpoints can, therefore,

only be described descriptively. ORR (95% CI) was 60% (52.9–66.3) with SG + pembro vs 53% (46.4–59.9) with TPC + pembro (OR 1.3; 95% CI 0.9–1.9). DOR (95% CI) was 16.5 (12.7–19.5) mo vs 9.2 (7.6–11.3) mo with SG + pembro vs TPC + pembro, respectively.  

Safety1

Overall, the safety profile of SG + pembro was consistent with the known safety profile of

each agent, with no additive toxicity observed. The rate of SAEs was higher with SG +

pembro vs TPC + pembro, however, the rate of TEAEs that led to treatment discontinuation

was lower (Table 3).

TEAEs that led to death occurred in seven patients in the SG + pembro arm, of which 3

were deemed treatment-related, and in 6 patients in the TPC + pembro arm, of which one

was deemed treatment-related (Table 3). TEAEs that led to death with SG + pembro were

pneumonia, sepsis, neutropenic sepsis, pulmonary embolism, and suicide (one each); there

were two deaths of unknown cause. TEAEs that led to death with TPC + pembro were

cardiac arrest, large intestine perforation, pneumonia, sepsis, post-procedural complication,

and death of unknown cause (one each).

Table 3. ASCENT-04: Safety Summary1

Abbreviations: AEs=adverse events.

aThe most common any-grade TEAEs that led to treatment discontinuation were pneumonitis (1%) for SG + pembro and peripheral neuropathy (5%), pneumonitis (3%), and thrombocytopenia (3%) for TPC + pembro.

bThere was no dose reduction for pembro per the protocol.

The most common any-grade and Grade ≥3 adverse events are presented in Table 4.

Table 4. ASCENT-04: Most Common (≥20%) TEAEsa1

Abbreviation: NA=not applicable.

aTEAEs were defined as any adverse events that began or worsened on or after the first dose date of study drug ≤30 days (or ≤90 days for SAEs) after the last dose date of study drug or the initiation of subsequent anticancer therapy (including crossover treatment).

Combined preferred terms of neutropenia include neutrophil count decreased, leukopenia includes white blood cell count decreased, anemia includes hemoglobin decreased and red blood cell count decreased, thrombocytopenia includes platelet count decreased, fatigue includes asthenia.

AESI are presented in Table 5; these events were consistent with the known safety profiles of each agent. No new safety concerns were observed.

Table 5. ASCENT-04: Adverse Events of Special Interest1

Abbreviation: NA=not applicable.

aAESI observed in ≥1% of patients in either group. bGrouped term.

References

1. Tolaney SM, De Azambuja E, Kalinsky K, et al. Sacituzumab govitecan plus pembrolizumab vs chemotherapy plus pembrolizumab in patients with previously untreated, PD-L1-positive, advanced or metastatic triple-negative breast cancer: primary results from the randomized, Phase 3 ASCENT-04/KEYNOTE-D19 study [Oral]. Presented at: American Society of Clinical Oncology (ASCO) Annual Meeting; 30 May-03 June, 2025; Chicago, IL.

2. Tolaney SM, De Azambuja E, Emens LA, et al. ASCENT-04/KEYNOTE-D19: phase 3 study of sacituzumab govitecan plus pembrolizumab vs treatment of physician’s choice plus pembro in first-line programmed death-ligand 1-positive metastatic triple-negative breast cancer [Poster 276TiP]. Presented at: European Society for Medical Oncology (ESMO) Congress; 9-13 September, 2022; Paris, France.

Abbreviations

1L=first line
2L=second line
AESI=adverse events of special interest
BICR=blinded independent
central review
CPS=combined positive score
DOR=duration of response
OS=overall survival
OR=odds ratio
ORR=objective response rate
Pembro=pembrolizumab
PFS=progression-free survival

RECIST v1.1=Response Evaluation Criteria in Solid Tumors version 1.1
SG=sacituzumab govitecan-hziy
TEAEs=treatment-emergent adverse events
TPC=treatment of physicians’ choice

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
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