GS-0201 + Sacituzumab Govitecan for Solid Tumors

Recruiting at 7 trial locations

Overseen By Gilead Clinical Study Information Center

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Gilead Sciences

Must not be taking: Antimicrobials, Corticosteroids, Antiarrhythmics, others

Disqualifiers: Pregnancy, CNS metastases, Cardiac disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 105 weeks

254 Participants Needed

Trial Summary

What is the purpose of this trial?

The main goal of this first in human (FIH) study is to learn about the safety and dosing of GS-0201 when given alone or in combination with sacituzumab govitecan (SG) in participants with advanced solid tumors. The primary objectives of this study are to: * To assess the safety and tolerability of GS-0201 as monotherapy and in combination with SG in participants with selected advanced solid tumors * To identify the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of GS-0201 as monotherapy and the MTD and/or the RP2D and dosing schedule of GS-0201 in combination with SG in participants with selected advanced solid tumors

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it mentions that ongoing therapy with prohibited medications is not allowed. You may need to stop certain treatments before starting the trial, especially if they are listed as prohibited.

What data supports the effectiveness of the drug Sacituzumab Govitecan for solid tumors?

Sacituzumab Govitecan has shown encouraging results in treating various advanced cancers, including breast cancer, by effectively delivering a cancer-fighting agent directly to tumor cells. It has been approved for use in patients with metastatic triple-negative breast cancer who have tried other treatments, indicating its potential effectiveness in solid tumors. ^{1 2 3 4 5}

What safety data exists for Sacituzumab Govitecan in humans?

Sacituzumab Govitecan, also known as Trodelvy or IMMU-132, has been studied for safety in various clinical trials for different types of cancers, including breast and other epithelial cancers. These studies have shown that it can be safely administered to patients, although like many cancer treatments, it may have side effects that need to be managed by healthcare providers. ^{1 2 3 4 6}

What makes the drug GS-0201 + Sacituzumab Govitecan unique for treating solid tumors?

GS-0201 combined with Sacituzumab Govitecan is unique because it targets solid tumors with a novel approach, using an antibody-drug conjugate (a targeted cancer therapy that links a drug to an antibody) to deliver chemotherapy directly to cancer cells, potentially reducing side effects compared to traditional chemotherapy. ^{7 8 9 10 11}

Research Team

Gilead Study Director

Principal Investigator

Gilead Sciences

Eligibility Criteria

This trial is for adults with advanced solid tumors who are physically capable of daily activity (ECOG status 0-1). They must understand the study and consent to it, have good blood, kidney, liver function, and measurable tumor growth. Participants need to provide tissue samples before and during treatment.

Inclusion Criteria

My blood clotting function is normal.

You need to have a sample of the tumor before starting treatment.

I am fully active or can carry out light work.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive GS-0201 as monotherapy or in combination with sacituzumab govitecan (SG) with dose escalation and expansion phases

Up to 105 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• GS-0201
• Sacituzumab Govitecan

Trial Overview The trial tests GS-0201 alone or combined with sacituzumab govitecan (SG) in treating advanced solid tumors. It aims to find out the safest dose that can be given without severe side effects (MTD) and suggest a Phase 2 dose.

Participant Groups

Group I: Part D: Cohort D2: Dose Expansion: GS-0201 + SG Experimental Treatment 2 Interventions

Participants with confirmed unresectable locally advanced or metastatic HR+/HER2- breast cancer will receive GS-0201 at the recommended Phase 2 dose (RP2D) in combination with SG.

Group II: Part D: Cohort D1: Dose Expansion: GS-0201 + SG Experimental Treatment 2 Interventions

Participants with confirmed unresectable locally advanced or metastatic triple negative breast cancer (mTNBC) will receive GS-0201 at the recommended Phase 2 dose (RP2D) in combination with SG.

Group III: Part C: Dose Escalation: GS-0201 + Sacituzumab Govitecan (SG) Experimental Treatment 2 Interventions

Participants will receive escalating doses of GS-0201 in combination with SG, until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol or up to 105 weeks, whichever occurs first.

Group IV: Part B: Cohort B2: GS-0201 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants with selected indications not included in cohort B1 will receive GS-0201 monotherapy at the recommended dose for expansion.

Group V: Part B: Cohort B1: GS-0201 Monotherapy Dose Expansion Experimental Treatment 1 Intervention

Participants with selected indications will receive GS-0201 monotherapy at the recommended dose for expansion.

Group VI: Part A: GS-0201 Monotherapy Dose Escalation Experimental Treatment 1 Intervention

Participants will receive escalating doses of GS-0201 monotherapy, until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol or up to 105 weeks, whichever occurs first.

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

Findings from Research

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and delivers a topoisomerase I inhibitor, showing promise in treating metastatic triple-negative breast cancer (mTNBC) after at least two prior therapies.

In April 2020, it received accelerated approval in the USA for mTNBC, and it is currently undergoing further clinical trials for various cancers, indicating its potential as a versatile treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. Syed, YY.[2021]

Sacituzumab govitecan (IMMU-132) demonstrated a predictable pharmacokinetic profile and manageable toxicity in patients with advanced epithelial cancers, with doses of 8 mg/kg (n=81) and 10 mg/kg (n=97) showing safety and efficacy.

The treatment resulted in objective responses in various cancer types, particularly metastatic triple-negative breast cancer, supporting the use of the 10 mg/kg dose for future clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Ocean, AJ., Starodub, AN., Bardia, A., et al.[2018]

Sacituzumab govitecan (SG) demonstrated effectiveness in treating relapsed or refractory metastatic triple-negative breast cancer (RM-TNBC), with a median overall survival of 12.9 months and an objective response rate of 34% based on an analysis of 412 patients across three trials.

The treatment was associated with significant adverse effects, particularly myelosuppression, with 46% of patients experiencing grade ≥3 neutropenia, and there were four treatment-related deaths reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. Cheng, SX., Chen, QC., Lin, GH., et al.[2023]

Sacituzumab govitecan, an antibody-drug conjugate targeting Trop-2, showed promising therapeutic activity in a phase I trial with 25 patients suffering from various metastatic solid cancers, achieving partial responses in two patients and stable disease in 16 others.

The maximum tolerated dose was determined to be 12 mg/kg for the first cycle, with lower doses (8 and 10 mg/kg) being safer for extended treatment, leading to acceptable toxicity levels and disease control for up to 36 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Starodub, AN., Ocean, AJ., Shah, MA., et al.[2022]

In a phase 1/2 trial involving 108 patients with heavily pretreated metastatic triple-negative breast cancer, sacituzumab govitecan-hziy demonstrated a response rate of 33.3%, with a median duration of response of 7.7 months, indicating its efficacy in this challenging patient population.

The treatment was associated with significant myelotoxic effects, including anemia and neutropenia, but overall survival was promising at a median of 13.0 months, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. Bardia, A., Mayer, IA., Vahdat, LT., et al.[2019]

Sacituzumab govitecan is an antibody-drug conjugate that targets Trop-2 and has shown a 33.3% overall response rate in patients with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies, based on a phase I/II study with 108 participants.

The treatment has a median duration of response of 7.7 months, and while it is generally well-tolerated, common side effects include nausea, neutropenia, and fatigue, indicating a need for monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. Seligson, JM., Patron, AM., Berger, MJ., et al.[2021]

In a study of 50 patients with HER2-positive advanced gastric or gastroesophageal junction cancer, the combination of trastuzumab, ramucirumab, and paclitaxel as a second-line treatment resulted in a median progression-free survival of 7.1 months and an overall survival of 13.6 months, indicating significant efficacy.

The treatment achieved a 54% objective response rate and a 96% disease control rate, with a manageable safety profile consistent with previous reports, suggesting it is a viable option for patients who have progressed after first-line therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trastuzumab Combined With Ramucirumab and Paclitaxel in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric or Gastroesophageal Junction Cancer. Kim, CG., Jung, M., Kim, HS., et al.[2023]

In a study of 252 Japanese gastric cancer patients, high HER2 expression was identified as a significant prognostic marker, indicating a higher risk of poor outcomes (HR=3.912) and suggesting that patients with high HER2 may benefit from targeted therapies.

The analysis revealed that a substantial number of patients exhibited genetic profiles indicating potential sensitivity to alternative treatments, such as platinum-based drugs or receptor tyrosine kinase inhibitors, highlighting the need for personalized treatment strategies based on genetic markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer. Yoshikawa, T., Aoyama, T., Sakamaki, K., et al.[2020]

In a phase II trial involving 43 patients with HER2-positive advanced gastric cancer, a treatment regimen combining pembrolizumab, trastuzumab, and chemotherapy achieved a high objective response rate of 76.7%, indicating strong efficacy as a first-line therapy.

The treatment demonstrated a median overall survival of 19.3 months and was well-tolerated, with no patients discontinuing due to immune-related adverse events, suggesting a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer. Lee, CK., Rha, SY., Kim, HS., et al.[2022]

In a study of 2,798 gastric carcinoma samples, HER2 positivity was found in 7.3% of cases and was significantly linked to factors like older age, male gender, and advanced cancer stages, suggesting its potential role in tumor progression and prognosis.

The study revealed that regional heterogeneity in HER2 expression is associated with weak HER2 overexpression (2+) and specific histological types, indicating that chromosome 17 polysomy may contribute to the variability in HER2 testing results.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A large cohort of consecutive patients confirmed frequent HER2 positivity in gastric carcinomas with advanced stages. Cho, J., Jeong, J., Sung, J., et al.[2022]

In a study of 56 patients with HER2-positive advanced gastric cancer, the combination of trastuzumab with the S-1 and cisplatin regimen resulted in a high confirmed response rate of 68% and a disease control rate of 94%.

The treatment demonstrated promising efficacy with median overall survival of 16 months and manageable side effects, including neutropenia in 36% of patients, indicating that this combination therapy is a viable option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). Kurokawa, Y., Sugimoto, N., Miwa, H., et al.[2021]

References

1. New Zealand pubmed.ncbi.nlm.nih.gov

Sacituzumab Govitecan: First Approval. [2021]

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

Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. [2018]

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

An integrated analysis of Sacituzumab govitecan in relapsed or refractory metastatic triple-negative breast cancer. [2023]

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

First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. [2022]

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

Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. [2019]

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

Sacituzumab Govitecan-hziy: An Antibody-Drug Conjugate for the Treatment of Refractory, Metastatic, Triple-Negative Breast Cancer. [2021]

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

Trastuzumab Combined With Ramucirumab and Paclitaxel in Patients With Previously Treated Human Epidermal Growth Factor Receptor 2-Positive Advanced Gastric or Gastroesophageal Junction Cancer. [2023]

8. Australia pubmed.ncbi.nlm.nih.gov

Comprehensive biomarker analyses identifies HER2, EGFR, MET RNA expression and thymidylate synthase 5'UTR SNP as predictors of benefit from S-1 adjuvant chemotherapy in Japanese patients with stage II/III gastric cancer. [2020]

9. England pubmed.ncbi.nlm.nih.gov

A single arm phase Ib/II trial of first-line pembrolizumab, trastuzumab and chemotherapy for advanced HER2-positive gastric cancer. [2022]

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

A large cohort of consecutive patients confirmed frequent HER2 positivity in gastric carcinomas with advanced stages. [2022]

11. England pubmed.ncbi.nlm.nih.gov

Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1). [2021]