A study of Sacituzumab Govitecan Versus Docetaxel in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC).

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Gilead Sciences Inc.

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

3 Mar 2022 → ongoing

Decision date (initial)

2024-07-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

Funding sources

Gilead Sciences Inc

External identifiers

EU CT number

2024-512148-50-00

EudraCT number

2021-003578-30

ClinicalTrials.gov

NCT05089734

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Pharmacokinetic, Efficacy

To compare the OS of SG versus docetaxel.

Secondary objectives 6

1. To compare the effect of SG versus docetaxel on the following: PFS as assessed by the investigator per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
2. ORR as assessed by the investigator per RECIST Version 1.1.
3. DOR as assessed by the investigator per RECIST Version 1.1.
4. Disease control rate (DCR) as assessed by the investigator per RECIST Version 1.1.
5. Safety and tolerability
6. QOL using NSCLC Symptom Assessment Questionnaire (NSCLC-SAQ).

Conditions and MedDRA coding

Non-small cell lung cancer

Regulatory references

Scientific advice from competent authorities

European Medicines Agency

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal [ULN], aspartate aminotransferase and alanine aminotransferase ≤ 2.5  ULN or ≤ 5  ULN if known liver metastases, and serum albumin > 3 g/dL). • Note: The investigator should follow local practice guidelines and/or the docetaxel label approved in the country of drug administration for assessing eligibility of patients for the study.
2. Creatinine clearance of at least 30 mL/min as assessed by the Cockcroft-Gault equation {Cockcroft 1976}.
3. Participants assigned male at birth and participants assigned female patientsat birth of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix 11.4.
4. Participants assigned female at birth or participants assigned male at birth 18 years of age or older, able to understand and give written informed consent
5. Life expectancy of 3 months or more
6. Pathologically documented NSCLC with documented evidence of Stage 4 NSCLC disease at the time of enrollment (based on the American Joint Committee on Cancer, Eighth Edition).
7. EGFR, ALK, and PD-L1 results are required prior to enrollment (see Section 6.3.10). Resulting for other actionable genomic alterations is recommended and to be performed as per local standard of care and availability of targeted treatment. For participants with squamous cell carcinoma, EGFR and ALK testing is optional.
8. Must have progressed after platinum-based chemotherapy in combination with anti- PD-1/PD-L1 antibody OR platinum-based chemotherapy and anti-PD-1/PD-L1 antibody (in either order) sequentially. • Note: Includes patients who received prior platinum-based chemoradiotherapy (with or without maintenance anti-PD-1/PD-L1 antibody) for Stage 3 disease. To be considered to have progressed during or after prior treatment with platinum-based chemotherapy, patients should have either received prior platinum-based chemotherapy in the recurrent/ metastatic setting or have experienced disease progression within 6 months of last dose of platinum-based chemotherapy administered as part of concurrent chemoradiation for Stage 3 disease or as neoadjuvant or adjuvant therapy. To be considered to have progressed during or after prior treatment with an anti-PD-1/PD-L1 antibody, patients should have either received this therapy in the recurrent/metastatic setting or have experienced disease progression during “maintenance” treatment following concurrent chemoradiation for Stage 3 disease. a) No additional treatments are allowed in the recurrent/metastatic setting for patients with no actionable genomic alterations. b) Patients with EGFR, ALK, or any other known actionable genomic alterations must have also received treatment with at least 1 locally approved and available TKI appropriate to the genomic alteration (see Appendix 8). c) Documented radiographic disease progression while on or after receiving the most recent treatment regimen for advanced or metastatic NSCLC.
9. Measurable disease based on computed tomography (CT) or magnetic resonance imaging (MRI) as assessed by the investigator in accordance with per RECIST Version 1.1. Tumor lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions. Historical images within 28 days of the screening visit may be accepted as a screening image if deemed acceptable in the opinion of the investigator.
10. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 (Appendix 11.6) before randomization
11. Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation (hemoglobin ≥ 9 g/dL, absolute neutrophil count ≥ 1500/mm3, and platelets ≥ 100,000/μL).

Exclusion criteria 16

1. Patients who meet any of the following exclusion criteria at screening/Day −1 are not eligible to be enrolled in this study (no waivers for patient eligibility will be offered or permitted): Mixed small-cell lung cancer and NSCLC histology.
2. Clinically severe pulmonary compromise resulting from intercurrent pulmonary illnesses including, but not limited to, any underlying pulmonary disorder (ie, pulmonary emboli within 3 months of enrollment, severe asthma, severe chronic obstructive pulmonary disease, restrictive lung disease, pleural effusion, etc); any autoimmune, connective tissue, or inflammatory disorders with pulmonary involvement (ie, rheumatoid arthritis, Sjogren syndrome, sarcoidosis, etc); or prior pneumonectomy.
3. Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they have stable CNS disease for at least 4 weeks prior to enrollment and all neurologic symptoms have returned to baseline, have no evidence of new or enlarging brain metastases, and are taking 10 mg/day or less of prednisone or its equivalent. All participants with carcinomatous meningitis are excluded regardless of clinical stability.
4. Met any of the following criteria for cardiac disease: a) Myocardial infarction or unstable angina pectoris within 6 months of enrollment. b) History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication); history of QT interval prolongation. c) New York Heart Association Class III or greater congestive heart failure or left ventricular ejection fraction of less than 40%
5. Active chronic inflammatory bowel disease (ulcerative colitis, Crohn’s disease) or gastrointestinal perforation within 6 months of enrollment
6. Active serious infection requiring antibiotics.
7. Positive HIV-1 or HIV-2 antibody with detectable viral load OR taking medications that may interfere with SN-38 metabolism.
8. Positive for hepatitis B surface antigen. Participants who test positive for hepatitis B core antibody will require hepatitis B virus DNA by quantitative polymerase chain reaction for confirmation of active disease.
9. Positive hepatitis C antibody and detectable hepatitis C viral load.
10. Other concurrent medical or psychiatric conditions that, in the investigator’s opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.
11. Positive serum pregnancy test (Appendix 11.4) or participants assigned female at birth who are lactating.
12. Known hypersensitivity to the study drugs, their metabolites, or formulation excipients.
13. Requirement for ongoing therapy with or prior use of any prohibited medications for SG and docetaxel as per Sections 5.7.1 and 5.12, respectively.
14. Received a prior anticancer biologic agent within 4 weeks prior to enrollment or have received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to enrollment and have not recovered (ie, > Grade 2 is considered not recovered) from AEs at the time of study entry.Participants participating in observational studies are eligible.
15. Previously received treatment with any of the following: a) Topoisomerase 1 inhibitors. Any agent including an ADC containing a chemotherapeutic agent targeting topoisomerase 1 b) Trop-2-targeted therapy c) Docetaxel as monotherapy or in combination with other agents
16. NSCLC that is eligible for definitive local therapy alone.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS is defined as the time from the date of randomization until death due to any cause in the Intent-to-Treat (ITT) Analysis Set.

Secondary endpoints 7

1. PFS is defined as the time from the date of randomization until the date of objective disease progression or death (whichever comes first) as assessed by the investigator per RECIST Version 1.1.
2. ORR is defined as the proportion of patientsparticipants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks later as assessed by the investigator per RECIST Version 1.1.
3. DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of PD or death from any cause (whichever comes first) as assessed by the investigator per RECIST Version 1.1.
4. DCR is defined as the proportion of patientsparticipants who achieve a CR, PR, or stable disease (SD) as assessed by the investigator per RECIST Version 1.1.
5. Incidence of treatment-emergent adverse events (TEAEs) and clinical laboratory abnormalities.
6. Time to first deterioration in shortness of breath domain as measured by NSCLC-SAQ.
7. Time to first deterioration in NSCLC-SAQ total score.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Gilead Sciences Inc.

Sponsor organisation

Gilead Sciences Inc.

Address

333 Lakeside Drive

City

Foster City

Postcode

94404-1147

Country

United States

Scientific contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Public contact point

Organisation

Gilead Sciences Inc.

Contact name

EU CT Support

Third parties 7

Locations

10 EU/EEA countries · 36 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 128 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

9 submissions — initial application plus substantial / non-substantial modifications