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Enzyme Inhibitor

Berzosertib + Standard Chemotherapy for Lung Cancer

Phase 1 & 2

Waitlist Available

Led By Liza C Villaruz

Research Sponsored by National Cancer Institute (NCI)

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Patients must have histologically confirmed NSCLC of predominantly squamous cell histology, stage IV (American Joint Committee on Cancer [AJCC] 8th edition)

Age >= 18 years. Because no dosing or adverse event data are currently available on the use of these drug combinations in patients < 18 years of age, children are excluded from this study, but will be eligible for future pediatric trials

Must not have

Patients with a history of allergic reactions attributed to compounds of similar chemical or biologic composition to berzosertib (M6620, VX-970), pembrolizumab, gemcitabine, carboplatin, or other agents used in study are not eligible

Patients must not have active, uncontrolled infections or recently received active vaccinations

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 12 months post treatment

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a combination of drugs to treat squamous cell non-small cell lung cancer. The drugs are given to see if they work better than just the chemotherapy drugs carboplatin and gemcitabine.

Who is the study for?

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.

What is being tested?

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.

What are the potential side effects?

Potential side effects include reactions related to immune system activation, such as inflammation in various organs, infusion-related reactions, fatigue, digestive issues like nausea or diarrhea, blood disorders including low counts of different types of cells which could increase infection risk.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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

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I am 18 years old or older.

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I am fully active or can carry out light work.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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

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I do not have any ongoing infections or recent vaccinations.

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I do not have severe bone marrow issues or major bleeding.

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I have not had a solid organ transplant or needed immunosuppressants for autoimmune disease in the last 2 years.

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I have not had chemotherapy for cancer that has spread.

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I am not pregnant or breastfeeding.

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I have not had a stem cell transplant from another person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 12 months post treatment

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 12 months post treatment

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 12 months post treatment for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Progression-free survival (PFS) (Phase 2)

Recommended phase 2 dose (RP2D) (Phase 1B)

Secondary study objectives

Overall response (OR)

Overall survival (OS)

PFS in the subset of patients with ATM-deficient squamous cell non-small cell lung cancer

+1 more

Other study objectives

ATM assay

Determination if features of whole exome and ribonucleic acid (RNA) sequencing are predictive OR, OS, or PFS

Inflammation

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Systemic infection

Clostridium difficile colitis

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Arm A (pembrolizumab, gemcitabine, carboplatin, M6620)Experimental Treatment7 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 Control6 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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Gemcitabine Hydrochloride

2005

Completed Phase 3

~5420

Biospecimen Collection

2004

Completed Phase 3

~2030