Berzosertib + Standard Chemotherapy for Lung Cancer

Not currently recruiting at 41 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors, CYP3A4 inducers

Disqualifiers: Severe illness, Autoimmune disease, others

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

Compensation: Varies

Number of Visits: 24

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment combination for patients with advanced stage IV squamous cell non-small cell lung cancer that has spread to other parts of the body. The researchers aim to determine the optimal dose of the chemotherapy drug carboplatin when combined with berzosertib (an experimental treatment), gemcitabine, and pembrolizumab. The goal is to assess whether this combination can halt cancer growth more effectively than current treatments. Patients with confirmed squamous cell lung cancer who have not received chemotherapy or immunotherapy for metastatic disease might be suitable candidates. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this novel combination therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but it mentions avoiding certain drugs that interact with berzosertib. It's important to discuss your current medications with the trial team to ensure there are no interactions.

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

Research has shown that berzosertib, when combined with gemcitabine, is generally well-tolerated by patients with advanced lung cancer. Studies found this combination manageable and promising for patients who have already tried other treatments, suggesting berzosertib might not cause severe side effects when used with other cancer drugs.

Carboplatin and gemcitabine, long-used chemotherapy drugs, are known to stop cancer cells from growing and spreading. Doctors are familiar with their side effects and know how to manage them.

Pembrolizumab, an immunotherapy drug, helps the body's immune system attack cancer cells. It is approved for use in various cancers, including lung cancer, and most patients tolerate it well.

Overall, research suggests these treatments together are safe and manageable. However, discussing any concerns with healthcare providers is important, as they can offer advice tailored to individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce berzosertib, a novel ATR kinase inhibitor, into the mix of standard chemotherapy options for lung cancer. Unlike typical treatments that primarily use drugs like carboplatin and gemcitabine, berzosertib targets a specific enzyme involved in DNA damage repair, potentially enhancing the effectiveness of chemotherapy. Arm A combines this new agent with pembrolizumab, an immunotherapy, offering a dual approach that not only attacks cancer cells directly but also boosts the immune response against them. This combination could lead to more efficient cancer cell eradication and improve patient outcomes compared to existing treatments.

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

Research shows that the drug berzosertib, when combined with gemcitabine, is generally safe and demonstrates early effectiveness in patients with advanced non-small cell lung cancer (NSCLC). In this trial, participants in Arm A will receive berzosertib, pembrolizumab, gemcitabine, and carboplatin. Arm B will test pembrolizumab, gemcitabine, and carboplatin without berzosertib. Pembrolizumab, an immunotherapy drug, helps the immune system identify and attack cancer cells. The chemotherapy drugs carboplatin and gemcitabine stop cancer cells from growing and spreading. This combination of treatments is being tested to determine if it can treat advanced squamous cell lung cancer more effectively than standard treatments alone. ^{2 3 4 5 6}

Who Is on the Research Team?

Liza C. Villaruz

Principal Investigator

University of Pittsburgh Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults over 18 with advanced stage IV squamous cell non-small cell lung cancer that hasn't spread widely can join this trial. They should have finished any early-stage chemotherapy a year before, have stable brain metastases if present, and normal organ function tests. Participants must not have had prior treatments for metastatic disease or be on certain drugs that interact with the trial medications.

Inclusion Criteria

I can provide tumor tissue samples or am willing to have a biopsy for study purposes.

I had platinum-based chemotherapy for early-stage lung cancer over a year ago and haven't had chemo or immunotherapy for metastatic disease.

My lung cancer is mainly squamous cell type and is stage IV.

Exclusion Criteria

I have no allergies to berzosertib, pembrolizumab, gemcitabine, carboplatin, or similar drugs.

I do not have any ongoing infections or recent vaccinations.

I should be cautious with Berzosertib due to my genetic condition affecting DNA repair.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lead-in Phase 1B

Determine the recommended phase 2 dose (RP2D) of carboplatin in combination with berzosertib and gemcitabine/pembrolizumab

Up to completion of cycle 1

Phase II Treatment

Patients receive pembrolizumab, gemcitabine, carboplatin, and berzosertib in cycles every 21 days for up to 4 cycles, followed by pembrolizumab and berzosertib for up to 9 months, and then pembrolizumab alone for up to 1 more year

Up to 21 months

Cycles every 21 days, then every 6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Berzosertib
• Carboplatin
• Gemcitabine Hydrochloride
• Pembrolizumab

Trial Overview The study is testing whether adding Berzosertib to the usual lung cancer treatments (Carboplatin and Gemcitabine) along with Pembrolizumab improves outcomes. It's in phases Ib/II to determine the best dose of Carboplatin and how well patients respond to this combination therapy.

How Is the Trial Designed?

Group I: Arm A (pembrolizumab, gemcitabine, carboplatin, M6620) Experimental Treatment 7 Interventions

Patients receive pembrolizumab IV over 30 minutes on day 1, gemcitabine hydrochloride IV over 30 minutes on days 1 and 8, carboplatin IV over 30 minutes on day 1, and berzosertib IV over 60 minutes on days 2 and 9. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab IV over 30 minutes on day 1 and berzosertib IV over 60 minutes on days 2 and 9. Cycles repeat every 21 days for up to 9 months in the absence of disease progression or unacceptable toxicity. Patients then receive pembrolizumab alone IV over 30 minutes on day 1. Cycles repeat every 6 weeks for up to 1 more year in the absence of disease progression or unacceptable toxicity. Patients undergo MRI scans and/or CT scans, and undergo blood specimen collection on study.

Group II: Arm B (pembrolizumab, gemcitabine, carboplatin) Active Control 6 Interventions

Patients receive pembrolizumab, gemcitabine, and carboplatin as in Arm A. Patients undergo MRI scans and/or CT scans, and undergo blood specimen collection on study.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S0169500221006048

Lung Cancer Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/34894455/

A phase 1b study evaluating the safety and preliminary ... Berzosertib plus gemcitabine was well tolerated in patients with advanced, pre-treated NSCLC. Based on the observed clinical efficacy, future clinical trials ...

3. nature.com nature.com/articles/s41416-021-01405-x

Phase 1 study of the ATR inhibitor berzosertib (formerly ... Berzosertib + gemcitabine was well tolerated in patients with advanced solid tumours and showed preliminary efficacy signs.

4. jamanetwork.com jamanetwork.com/journals/jamaoncology/fullarticle/2810382

Berzosertib Plus Topotecan vs Topotecan Alone in Patients ... The findings of the randomized clinical trial indicate that the addition of berzosertib to topotecan therapy does not improve progression-free survival among ...

5. emdserono.com emdserono.com/us-en/company/news/press-releases/emd-serono-advances-atr-inhibitor-berzosertib-in-small-cell-lung-cancer-12-04-2021.html

EMD Serono Advances ATR Inhibitor Berzosertib in Small ... US National Cancer Institute led Phase II clinical study met its primary objective with 36% confirmed ORR, and showed durable responses.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02589522?term=VE-822%20OR%20VX-970%20OR%20M6620%20OR%20berzosertib&viewType=Table&rank=2

Study Details | Testing the Safety of M6620 (VX-970) When ... An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...