Sacituzumab Govitecan + Berzosertib for Small Cell Lung Cancer

Overseen By Linda C Sciuto, R.N.

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A inhibitors, UGT1A1 inhibitors

Disqualifiers: Symptomatic brain metastasis, Myelosuppressive disorders, others

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

Compensation: Varies

Number of Visits: 4

Duration: Until disease progression or intolerable side effects

120 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to identify a safe and effective drug combination for individuals with small cell lung cancer and cancers resistant to PARP inhibitors, which are difficult to treat. Researchers are testing whether sacituzumab govitecan (an antibody-drug conjugate) and berzosertib (an experimental treatment) can shrink these tumors. The trial seeks participants with solid tumors, small cell lung cancer, or specific resistant cancers, who have not recently undergone chemotherapy or major surgery. Participants will receive the drugs intravenously and undergo regular exams and scans to monitor progress.

As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot be on other investigational drugs or certain medications that affect liver enzymes. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found sacituzumab govitecan to be well-tolerated, meaning it did not cause severe side effects in most people. It showed positive results in patients who had already tried other treatments for non-small-cell lung cancer. The FDA has approved sacituzumab govitecan for treating certain stages of small cell lung cancer, indicating its safety is well understood.

Berzosertib, when combined with sacituzumab govitecan, aims to treat tumors that don't respond to other treatments. Although specific safety data on using these drugs together is limited, ongoing research suggests promise.

Since the trial is in its early stages, the main focus is on understanding the safety of these drugs when used together. Early-stage trials closely monitor participants to check for side effects and ensure the treatment is safe for humans. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Sacituzumab Govitecan and Berzosertib for small cell lung cancer because these treatments work in novel ways compared to standard options like chemotherapy. Sacituzumab Govitecan is unique because it combines an antibody that targets tumor cells with a cancer-killing agent, delivering treatment directly to the cancer. Berzosertib, a new player in the field, inhibits a protein that cancer cells rely on to repair their DNA, making these cells more vulnerable. Together, they offer a targeted approach that could be more effective and less toxic than conventional therapies.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

This trial will evaluate the combination of sacituzumab govitecan and berzosertib for treating small cell lung cancer. Research has shown that this combination may help treat small cell lung cancer and tumors unresponsive to PARP inhibitors. In earlier studies, sacituzumab govitecan shrank tumors in 60% of patients who had already received multiple treatments for small cell lung cancer. Recognized as a Breakthrough Therapy, this drug has shown potential to be highly effective. When combined with sacituzumab govitecan, berzosertib addresses issues like stress on cancer cells and resistance to chemotherapy, offering another approach to combat cancer. These findings suggest that this combination could be a strong treatment option for aggressive cancers that are difficult to treat with current methods. ^{2 3 6 7 8}

Who Is on the Research Team?

Anish Thomas, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

Adults with certain advanced cancers, including small cell lung cancer and solid tumors resistant to PARP inhibitors. Participants must have a lesion safe for biopsy, measurable disease, stable brain metastases if present, good organ function, and no major treatments within specific time frames before the trial. They should not have severe genetic disorders affecting drug processing or uncontrolled illnesses that could hinder compliance.

Inclusion Criteria

I can take care of myself and perform daily activities.

My brain metastases are stable and not causing new symptoms.

I am willing to have a biopsy and have at least one lesion that can safely be biopsied.

Exclusion Criteria

I have a blood disorder affecting my bone marrow or acute myeloid leukemia.

I have a specific genetic variant that affects drug processing.

I am infected with Hepatitis C.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive sacituzumab govitecan on days 1 and 8 and berzosertib on days 2 and 9 of each 21-day cycle

Until disease progression or intolerable side effects

2 visits per cycle (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 month after treatment, then every 3 months for life

1 visit (in-person), then contact by phone or email

What Are the Treatments Tested in This Trial?

Interventions

• Berzosertib
• Sacituzumab Govitecan

Trial Overview The study is testing a combination of two drugs: Sacituzumab Govitecan and Berzosertib in patients with aggressive cancers like small cell lung cancer. The goal is to find a safe dosage that can shrink these tumors. Patients will receive the drugs intravenously on set days over 21-day cycles as long as they benefit without intolerable side effects.

How Is the Trial Designed?

Group I: 2/Phase II Experimental Treatment 2 Interventions

Sacituzumab Govitecan and Berzosertib treatment with identified MTD based on phase I.

Group II: 1/Phase I Experimental Treatment 2 Interventions

Dose escalated Sacituzumab Govitecan and Berzosertib

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

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 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]

A total of 1,884 adverse event reports related to sacituzumab govitecan were analyzed, identifying 114 adverse event signals, with most occurring within 30 days of treatment initiation, highlighting the importance of monitoring for early reactions.

Risk factors for hospitalization due to adverse events included being male and experiencing conditions like colitis, febrile neutropenia, and sepsis, indicating specific patient profiles that may require closer observation during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Postmarketing safety of Sacituzumab govitecan: a pharmacovigilance study based on FDA adverse event reporting system (FAERS). Li, X., Zhang, L., Hu, S., et al.[2023]

Sacituzumab govitecan (SG) showed a clinically significant advantage over chemotherapy for treating HR+/HER2- metastatic breast cancer, providing an increase of 0.284 life years and 0.217 quality-adjusted life years (QALYs).

However, SG was not considered cost-effective at the current pricing, with an incremental cost-effectiveness ratio (ICER) of $612,772/QALY, indicating that substantial price reductions would be necessary for it to be deemed cost-effective from a third-party payer perspective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-effectiveness of sacituzumab govitecan in hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. Shi, D., Li, Y., Liang, X., et al.[2023]

Sacituzumab govitecan-hziy (TRODELVY) received accelerated FDA approval for treating metastatic triple-negative breast cancer (mTNBC) based on a trial involving 108 patients, showing an objective response rate of 33.3% and a median duration of response of 7.7 months.

The safety profile was assessed in a larger group of 408 patients, with common side effects including nausea, neutropenia, and fatigue, occurring in 25% or more of patients, indicating that while effective, the treatment can have significant adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Sacituzumab Govitecan-hziy for Third-line Treatment of Metastatic Triple-negative Breast Cancer. Wahby, S., Fashoyin-Aje, L., Osgood, CL., et al.[2022]

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]

In a study involving 60 patients with advanced solid tumors, the combination of berzosertib and gemcitabine was found to be well tolerated, with a recommended Phase 2 dose established for this combination.

The treatment showed preliminary signs of efficacy, with many patients achieving either a partial response or stable disease, indicating potential benefits for those with resistant or refractory tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase 1 study of the ATR inhibitor berzosertib (formerly M6620, VX-970) combined with gemcitabine ± cisplatin in patients with advanced solid tumours. Middleton, MR., Dean, E., Evans, TRJ., et al.[2023]

In a study of 50 patients with metastatic small cell lung cancer (mSCLC) who had been heavily pretreated, sacituzumab govitecan demonstrated a 14% objective response rate, with 60% of patients showing tumor shrinkage, indicating its potential efficacy as a treatment option.

The treatment was found to be generally safe, with manageable side effects; however, significant adverse events included neutropenia (34%) and fatigue (13%). This suggests that while effective, careful monitoring for side effects is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Gray, JE., Heist, RS., Starodub, AN., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04826341

NCT04826341 | A Phase I/II Study of Sacituzumab ... A combination of berzosertib with sacituzumab govitecan will provide an effective therapeutic option for patients with PARPi resistant tumors and chemotherapy- ...

2. gilead.com gilead.com/news/news-details/2024/us-fda-grants-breakthrough-therapy-designation-to-trodelvy-sacituzumab-govitecan-hziy-for-second-line-treatment-of-extensive-stage-small-cell-lung-cancer

U.S. FDA Grants Breakthrough Therapy Designation to ... U.S. FDA Grants Breakthrough Therapy Designation to Trodelvy sacituzumab govitecan hziy for Second Line Treatment of Extensive Stage Small ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10524218/

A Phase I Clinical Trial - PMC Targeting replication stress and chemotherapy resistance with a combination of Sacituzumab Govitecan and Berzosertib: a Phase I clinical trial.

4. withpower.com withpower.com/trial/phase-2-small-cell-lung-carcinoma-8-2021-07b59

Sacituzumab Govitecan + Berzosertib for Small Cell Lung ... Sacituzumab Govitecan has shown effectiveness in heavily pretreated small cell lung cancer patients, with 60% of patients experiencing tumor shrinkage and a ...

5. askgileadmedical.com askgileadmedical.com/docs/trodelvy/trodelvy-use-in-patients-with-sclc

(sacituzumab govitecan-hziy) - Use in Patients With SCLC Grade ≥3 TEAEs were reported in 74.4% of patients; most frequent were neutropenia (44.2%), diarrhea (9.3%), hyponatremia (7%), anemia (4.7%), stomatitis (4.7%), ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/28548889/

Therapy of Advanced Non-Small-Cell Lung Cancer With an ... IMMU-132 was well-tolerated and induced durable responses in heavily pretreated patients with metastatic NSCLC. This ADC should be studied further in this ...

7. aacrjournals.org aacrjournals.org/clincancerres/article/31/8/1390/754522/The-Mode-of-Action-and-Clinical-Outcomes-of

The Mode of Action and Clinical Outcomes of Sacituzumab ... Sacituzumab govitecan (SG; hRS7-CL2A-SN-38; Trodelvy) is a next-generation ADC designed to improve payload delivery to the tumor. It is approved in patients ...

8. researchgate.net researchgate.net/publication/275525029_Sacituzumab_Govitecan_IMMU-132_an_Anti-Trop-2SN-38_Antibody-Drug_Conjugate_Characterization_and_Efficacy_in_Pancreatic_Gastric_and_Other_Cancers

Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 ... Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) made from a humanized anti-Trop-2 monoclonal antibody (hRS7) conjugated ...