Sacituzumab Govitecan Combo for Lung Cancer

(EVOKE-02 Trial)

Recruiting at 122 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Gilead Sciences

Must not be taking: Steroids, Immunosuppressants

Disqualifiers: Active second malignancy, Autoimmune, Transplant, CNS metastases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 21-day cycles

193 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical study is to learn more about the study drug, sacituzumab govitecan-hziy (SG), and its dosing in combination with pembrolizumab or pembrolizumab and a platinum agent (carboplatin or cisplatin), in participants with advanced or metastatic (cancer that has spread) non-small-cell lung cancer (NSCLC).

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot have received systemic anticancer treatment in the past 6 months, and you should not be on chronic systemic steroid therapy.

What data supports the effectiveness of the drug Sacituzumab Govitecan Combo for Lung Cancer?

Research shows that combining pembrolizumab (an immune therapy drug) with platinum-based chemotherapy, like carboplatin or cisplatin, improves outcomes in advanced non-small cell lung cancer compared to chemotherapy alone. This suggests that adding Sacituzumab Govitecan to a similar combination might also be effective. ^{1 2 3 4 5}

Is the Sacituzumab Govitecan Combo for Lung Cancer generally safe in humans?

The combination of pembrolizumab with carboplatin and other drugs has been studied for lung cancer, showing that while it can improve survival, it also increases the risk of serious side effects. These side effects can include severe adverse events, which are more common when additional drugs like atezolizumab are added to the treatment. ^{1 6 7 8 9}

What makes the Sacituzumab Govitecan combo drug unique for lung cancer?

The Sacituzumab Govitecan combo is unique because it combines an antibody-drug conjugate (Sacituzumab Govitecan) with traditional chemotherapy agents (Carboplatin, Cisplatin) and an immunotherapy drug (Pembrolizumab), potentially offering a novel approach by targeting cancer cells directly while also boosting the immune system to fight lung cancer. ^{1 2 10 11 12}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with advanced or metastatic non-small-cell lung cancer (NSCLC) who haven't had systemic treatment for it. They should have a good performance status, meaning they can carry out daily activities with little or no assistance. Their blood counts and liver function need to be within certain ranges, and their disease must be measurable on scans.

Inclusion Criteria

My cancer can be measured on scans.

My cancer can be measured on scans according to specific criteria.

I haven't had any systemic treatment for my advanced lung cancer.

Exclusion Criteria

I have an immune system disorder or am on long-term steroids.

I have been treated for an autoimmune disease in the last 2 years.

I haven't had any cancer treatment in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Participants receive sacituzumab govitecan at de-escalating dose levels with pembrolizumab and carboplatin or cisplatin to determine the recommended phase 2 dose

21-day cycles

Visits on Days 1 and 8 of each cycle

Treatment

Participants receive sacituzumab govitecan at the recommended phase 2 dose with pembrolizumab and a platinum agent (carboplatin or cisplatin) based on cohort assignment

21-day cycles

Visits on Days 1 and 8 of each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

Treatment Details

Interventions

• Carboplatin
• Cisplatin
• Pembrolizumab
• Sacituzumab Govitecan-hziy (SG)

Trial Overview Researchers are testing the drug sacituzumab govitecan-hziy (SG), alone and in combination with pembrolizumab and either carboplatin or cisplatin. The study aims to find effective dosing regimens for patients with NSCLC that has spread beyond its original site.

Participant Groups

Group I: Sacituzumab Govitecan-hziy (SG) + Pembrolizumab (Cohort A) Experimental Treatment 2 Interventions

Participants assigned to Cohorts A according to tumor proportion score (TPS) status will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle.

Group II: SG + Pembrolizumab + Cisplatin Safety Run-in (Optional) Experimental Treatment 3 Interventions

Participants will receive SG (either 10 mg/kg or 7.5 mg/kg) on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + cisplatin 75 mg/m\^2 on Day 1 of a 21-day cycle.

Group III: SG + Pembrolizumab + Cisplatin (Cohort E) Experimental Treatment 3 Interventions

Participants assigned to Cohort E will receive SG RP2D, as determined following safety review of Cohorts C and D, on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + cisplatin 75 mg/ m\^2 on Day 1 of a 21-day cycle.

Group IV: SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort D) Experimental Treatment 4 Interventions

Participants assigned to Cohort D according to disease status will receive SG RP2D as determined during the safety run-in cohorts on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin AUC5 or cisplatin 75 mg/m\^2 as determined during the safety run-in cohorts on Day 1 of a 21-day cycle.

Group V: SG + Pembrolizumab + Carboplatin or Cisplatin (Cohort C) Experimental Treatment 4 Interventions

Participants assigned to Cohort C according to disease status will receive SG RP2D as determined during the safety run-in cohorts on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin AUC5 or cisplatin 75 mg/m\^2 as determined during the safety run-in cohorts on Day 1 of a 21-day cycle.

Group VI: SG + Pembrolizumab + Carboplatin Safety Run-in Experimental Treatment 3 Interventions

Participants will receive SG (de-escalating dose levels: 10.0 mg/kg, 7.5 mg/kg, or 5.0 mg/kg) on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle + carboplatin area under the concentration versus time curve (AUC)5 on Day 1 of a 21-day cycle.

Group VII: SG + Pembrolizumab (Cohort B) Experimental Treatment 2 Interventions

Participants assigned to Cohorts B according to TPS status will receive SG 10 mg/kg on Days 1 and 8 of a 21-day cycle + pembrolizumab 200 mg on Day 1 of a 21-day cycle.

Carboplatin is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Paraplatin for:

• Ovarian cancer
• Testicular cancer
• Lung cancer
• Head and neck cancer
• Brain cancer

Approved in European Union as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer

Approved in Canada as Carboplatin for:

• Ovarian cancer
• Small cell lung cancer
• Testicular cancer

Who Is Running the Clinical Trial?

Gilead Sciences

Lead Sponsor

Trials

1,150

Recruited

878,000+

Daniel O'Day

Gilead Sciences

Chief Executive Officer since 2019

MBA from Columbia University

Dietmar Berger

Gilead Sciences

Chief Medical Officer

MD and PhD from Albert-Ludwigs University School of Medicine

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Findings from Research

In a real-life study of 121 patients with advanced non-squamous non-small cell lung cancer, the combination of pembrolizumab and chemotherapy resulted in a median progression-free survival of 9 months and overall survival of 20.6 months, demonstrating its efficacy as a first-line treatment.

The treatment was generally well-tolerated, with manageable side effects; however, 17.5% of patients experienced grade 3-4 adverse events, and there were two treatment-related deaths, indicating the need for careful monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). Renaud, E., Ricordel, C., Corre, R., et al.[2023]

In a phase II study involving 167 patients with stage IV squamous non-small-cell lung cancer, the combination of necitumumab with paclitaxel-carboplatin chemotherapy resulted in a higher objective response rate (48.9%) compared to chemotherapy alone (40.0%).

The safety profile of necitumumab was consistent with other EGFR monoclonal antibodies, with increased rates of hypomagnesemia and rash, but overall adverse events were low, indicating that necitumumab can be safely combined with chemotherapy for improved treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. Spigel, DR., Luft, A., Depenbrock, H., et al.[2022]

In a pooled analysis of 444 patients with PD-L1-negative advanced/metastatic non-small cell lung cancer (NSCLC), pembrolizumab combined with chemotherapy significantly improved overall survival (hazard ratio 0.63) and progression-free survival (hazard ratio 0.68) compared to chemotherapy alone.

Despite high rates of adverse events (99.2% in the pembrolizumab group), the combination therapy was manageable and resulted in an impressive objective response rate of 87.5% and a 3-year overall survival rate of 100% for patients completing 2 years of treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. Borghaei, H., Langer, CJ., Paz-Ares, L., et al.[2021]

In a study of 123 patients with advanced nonsquamous NSCLC, the combination of pembrolizumab and pemetrexed-carboplatin (PC) significantly improved the objective response rate (56.7% vs. 30.2% with PC alone) and progression-free survival (PFS) compared to PC alone, with a hazard ratio (HR) of 0.53.

The updated analysis showed a favorable overall survival (OS) hazard ratio of 0.56 for the pembrolizumab plus PC group, indicating a significant survival benefit, although 41% of patients experienced grade 3 to 5 treatment-related adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. Borghaei, H., Langer, CJ., Gadgeel, S., et al.[2022]

In a study involving 74 patients with advanced non-small-cell lung cancer, the combination of pembrolizumab with platinum-based chemotherapy showed promising antitumor activity, with objective response rates of 48% to 75% across different treatment cohorts.

The treatment was generally well-tolerated, with no dose-limiting toxicities reported, although 40% to 46% of patients experienced grade 3/4 adverse events, which aligns with the known side effects of platinum-based chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. Gadgeel, SM., Stevenson, JP., Langer, CJ., et al.[2019]

The combination of pemetrexed, platinum, and pembrolizumab shows manageable toxicity, with most severe adverse events occurring early in treatment and resolving within two weeks, indicating a favorable safety profile for long-term use.

While there was a slightly higher incidence of renal toxicity in patients receiving the pembrolizumab combination compared to those on pemetrexed alone, this did not increase with longer treatment durations, supporting the regimen's safety in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. Garon, EB., Aerts, J., Kim, JS., et al.[2023]

In a study of 245 treatment-naïve Chinese patients with stage IV non-squamous non-small-cell lung cancer, the addition of atezolizumab to carboplatin and nab-paclitaxel significantly improved progression-free survival (12.98 months vs. 10.89 months) and overall survival (38.04 months vs. 33.59 months) compared to chemotherapy alone.

However, this combination therapy also led to a higher incidence of grade ≥3 adverse events, with 84% of patients in the atezolizumab group experiencing severe side effects, highlighting the need to balance efficacy with safety in treatment decisions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab plus carboplatin and nab-paclitaxel versus carboplatin and nab-paclitaxel as treatments for Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients: A retrospective analysis. Chen, Y., Kang, S., Yan, M.[2022]

This study is the first to evaluate the combination of necitumumab with pembrolizumab and platinum-based chemotherapy in patients with untreated squamous cell lung cancer (SqCLC), aiming to enhance tumor immunity and therapeutic effects.

The trial will assess safety and efficacy, with 42 patients enrolled in phase II to determine the overall response rate and other important outcomes like progression-free survival and overall survival.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). Miyanaga, A., Asahina, H., Watanabe, S., et al.[2023]

Combination treatments using platinum compounds and etoposide show median survival rates of 7 to 10 months for extensive-stage and 15 to 20 months for limited-stage small cell lung cancer, indicating their effectiveness in improving patient outcomes.

Adding paclitaxel to platinum/etoposide regimens has shown promising results in early studies, with good activity and manageable toxicity, and ongoing phase III trials aim to clarify its role in enhancing treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. Hainsworth, JD., Greco, FA.[2015]

References

1. China pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus pemetrexed-carboplatin combination in first-line treatment of advanced non-squamous non-small cell lung cancer: a multicenter real-life study (CAP29). [2023]

2. United States pubmed.ncbi.nlm.nih.gov

An Open-Label, Randomized, Controlled Phase II Study of Paclitaxel-Carboplatin Chemotherapy With Necitumumab Versus Paclitaxel-Carboplatin Alone in First-Line Treatment of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Pembrolizumab plus chemotherapy versus chemotherapy alone in patients with advanced non-small cell lung cancer without tumor PD-L1 expression: A pooled analysis of 3 randomized controlled trials. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

24-Month Overall Survival from KEYNOTE-021 Cohort G: Pemetrexed and Carboplatin with or without Pembrolizumab as First-Line Therapy for Advanced Nonsquamous Non-Small Cell Lung Cancer. [2022]

5. Ireland pubmed.ncbi.nlm.nih.gov

Pembrolizumab and platinum-based chemotherapy as first-line therapy for advanced non-small-cell lung cancer: Phase 1 cohorts from the KEYNOTE-021 study. [2019]

6. Ireland pubmed.ncbi.nlm.nih.gov

Safety of pemetrexed plus platinum in combination with pembrolizumab for metastatic nonsquamous non-small cell lung cancer: A post hoc analysis of KEYNOTE-189. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Atezolizumab plus carboplatin and nab-paclitaxel versus carboplatin and nab-paclitaxel as treatments for Chinese, treatment-naïve, stage IV, non-squamous, non-small-cell lung cancer patients: A retrospective analysis. [2022]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Phase I dose escalation study of carboplatin to a fixed dose of irinotecan as first-line treatment of small cell lung cancer. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

A Phase I/II Study of Necitumumab Plus Pembrolizumab, Nab-Paclitaxel, and Carboplatin for Previously Untreated Advanced Squamous Non-Small Cell Lung Cancer Study: (NEJ048A/NEXUS). [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Phase 1/2 dose escalating study of twice-monthly pemetrexed and gemcitabine in patients with advanced cancer and non-small cell lung cancer. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Triplet chemotherapy with gemcitabine, a platinum, and a third agent in the treatment of advanced non-small cell lung cancer. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

The current role and future prospects of paclitaxel in the treatment of small cell lung cancer. [2015]