A Phase I/II Study of Sacituzumab Govitecan Plus Berzosertib in Small Cell Lung Cancer, Extra-Pulmonary Small Cell Neuroendocrine Cancer and Homologous Recombination-Deficient Cancers Resistant to PARP Inhibitors

NCT04826341 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 10000144000144-C
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Small cell lung cancer and PARP inhibitor resistant tumors are aggressive cancers. Current treatments for people with these tumors yield little benefit. Researchers want to see if a combination of drugs can help. Objective: To find a safe combination of sacituzumab govitecan and berzosertib and to see if this will cause small cell lung cancer and PARP inhibitor resistant tumors to shrink. Eligibility: People ages 18 and older with a solid tumor, small cell lung cancer, or a homologous recombination-deficient cancer that is resistant to PARP inhibitors Design: Participants will be screened with: Standard clinical exams and tests EKG to test the heart Medical documentation to confirm cancer diagnosis Participants will get sacituzumab govitecan by vein on days 1 and 8 of each 21-day cycle. They will get berzosertib by vein on days 2 and 9. Treatment will continue as long as they can tolerate the drugs and their tumors are either stable or getting better. Before treatment and at least once per cycle, participants will have a physical exam and blood tests. Before treatment and every 2 or 3 cycles, they will have a CT scan. They will have a contrast agent injected into a vein for the scan. Participants will give blood and hair samples and tumor biopsies for research. Biopsies will be taken with a small needle under imaging guidance. After they stop treatment, participants will have a visit 1 month later. They will then be contacted by phone or email every 3 months for the rest of their lives.

Conditions

HRD Cancer; Advanced Solid Tumors; SCLC

Keywords

PARPi resistance; ATR inhibition; targeted DNA-damaging chemotherapy; Antibody-Drug Conjugate; topoisomerase-I inhibiting camptothecin

Outcome Measures

Primary Outcomes (2)

• Phase II: ORR

  In phase II, in each cohort, the fraction of participants who experience a PR or CR will be reported along with a 95% confidence interval.

  Disease progression

• Phase I: MTD

  In phase I, the toxicities identified at each dose level will be reported, by dose level, type, and grade.

  Phase I

Secondary Outcomes (5)

• Progression free survival (PFS)

  Disease progression

• Overall survival (OS)

  Death

• Toxicity grade and type

  during treatment

• Duration of response

  Disease progression

• Safety and tolerability

  during treatment

Study Arms (2)

1/Phase I

EXPERIMENTAL

Dose escalated Sacituzumab Govitecan and Berzosertib

Drug: Berzosertib; Drug: Sacituzumab Govitecan

2/Phase II

EXPERIMENTAL

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

Drug: Berzosertib; Drug: Sacituzumab Govitecan

Interventions

Berzosertib DRUG

Berzosertib will be supplied as 20 mg/mL M6620 to be diluted with 5% dextrose in water solution before intravenous infusion.

1/Phase I; 2/Phase II

Sacituzumab Govitecan DRUG

Sacituzumab Govitecan will be administered as an intravenous infusion once weekly on Days 1 and 8 of 21-day treatment cycles.

1/Phase I; 2/Phase II

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All phases and cohorts
• Subjects must not have received chemotherapy or undergone major surgery within 2 weeks and radiotherapy within 24 hours prior to cycle 1 day 1.
• Age \>=18 years. Because no dosing or adverse event data are currently available on the use of sacituzumab govitecan in combination with and berzosertib in participants \<18 years of age, children are excluded from this study, but will be eligible for future pediatric trials.
• ECOG performance status \<=2
• Participants must have adequate organ and marrow function as defined below:
• leukocytes \>=3,000/mcL
• Hemoglobin \>=9.0g/dL
• absolute neutrophil count \>=1,500/mcL
• platelets \>=100,000/mcL
• total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) \<=2.5 X institutional upper limit of normal
• creatinine within normal institutional limits
• creatinine clearance \>=30 mL/min/1.73 m2 for participants with creatinine levels above institutional normal
• (calculated by Cockcroft-Gault formula).
• Participants with neurologically stable brain metastases defined as asymptomatic metastasis, or treated metastasis having no evidence of progression or hemorrhage for at least 2 weeks after treatment (including brain radiotherapy) may be included. Participants must be off any systemic corticosteroids for the treatment of brain metastases for at least 7 days prior to enrollment.

You may not qualify if:

• Participants who are receiving any other investigational agents or concurrent systemic anti-cancer therapies.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs or other agents used in study.
• Participants with symptomatic brain metastasis.
• Participants who require treatment with strong inhibitors or inducers of CYP3A or with UGT1A1 inhibitors during the planned period of investigational treatment with sacituzumab govitecan.
• Participants known to be homozygous for the UGT1A1\*28 variant allele with severely reduced UGT1A1 activity.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant individuals are excluded from this study because study drugs have the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with study drugs, breastfeeding should be discontinued if the mother is treated with the study drugs. These potential risks may also apply to other agents used in this study.
• Participants with myelosuppressive disorders or acute myeloid leukemia.
• HIV positive participants with the following exception: Patients with long-standing (\>5 years) HIV on antiretroviral therapy \> 1 month (undetectable HIV viral load and CD4 count \> 150 cells/microL) may be eligible if the principal investigator determines no anticipated clinically significant drug-drug interactions.
• Participants with evidence of chronic hepatitis B virus (HBV) infection, unless the HBV viral load is undetectable and participant is on suppressive therapy, if indicated.
• HCV infected participants with the following exceptions: Participants with a history of hepatitis C virus (HCV) infection must have been treated and cured. For participants with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

berzosertib; sacituzumab govitecan

Study Officials

• Anish Thomas, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 31, 2021
• First Posted: April 1, 2021
• Study Start: September 20, 2021
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2029
• Last Updated: May 5, 2026

Record last verified: 2026-04-20

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Clinical data available during the study and indefinitely.@@@@@@@@@@@@Genomic data are available once genomic data are uploaded per protocol GDS plan for as long as database is active.
• Access Criteria: Clinical data will be made available via subscription to BTRIS and with the permission of the study PI. @@@@@@Genomic data are made available via dbGaP through requests to the data custodians.

Locations

US (1)