A Study Evaluating the Overall Survival of Patients with Extensive Stage Small Cell Lung Cancer Receiving Trilaciclib or Placebo prior to Topotecan Chemotherapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Pharmacosmos A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

27 Sep 2023 → ongoing

Decision date (initial)

2023-05-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate whether trilaciclib administered prior to topotecan is non-inferior to placebo administered prior to topotecan with regard to overall survival (OS) in patients with Extended Stage Small Cell Lung Cancer (ES-SCLC).

Secondary objectives 7

1. To assess the effects of trilaciclib on anti-tumor endpoints (progression-free survival [PFS], objective response rate [ORR], and duration of response [DOR]).
2. To assess the effects of trilaciclib on the neutrophil lineage compared with placebo when administered prior to topotecan.
3. To assess the effects of trilaciclib on the RBC lineage compared with placebo when administered prior to topotecan.
4. To assess the effects of trilaciclib on the platelet lineage compared with placebo when administered prior to topotecan.
5. To assess the effects of trilaciclib on hospitalizations due to chemotherapy-induced myelosuppression compared with placebo when administered prior to topotecan.
6. To assess the effects of trilaciclib on chemotherapy dosing compared with placebo when administered prior to topotecan.
7. To collect and summarize safety and tolerability data for trilaciclib when administered prior to topotecan

Conditions and MedDRA coding

Extensive Stage Small Cell Lung Cancer

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Age ≥18 years
2. Resolution of nonhematologic toxicities from prior systemic therapy, radiation therapy, or surgical procedures to National Cancer Institute Common Terminology Criteria (NCI-CTCAE) version 5.0 ≤ Grade 1. Grade 2 toxicities that would not constitute a safety risk for subsequent treatment and are not expected to resolve in a timely manner (e.g., alopecia, neuropathy, electrolyte abnormalities, immuno-oncology complications) based on the investigator’s judgement are acceptable.
3. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies
4. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol
5. ES-SCLC with confirmed diagnosis of SCLC by histology or cytology, preferably including the presence of neuroendocrine features by immunohistochemistry
6. Progression during or after prior first- or second-line chemotherapy
7. Measurable or evaluable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
8. Known sensitivity status (sensitive or resistant) to first- line therapy at enrollment
9. Considered to be eligible to receive topotecan chemotherapy in the Investigator’s judgment
10. ECOG performance status of 0-2
11. Adequate organ function as demonstrated by the laboratory values listed in the protocol

Exclusion criteria 16

1. History of topotecan (or other topoisomerase I inhibitor) or trilaciclib treatment for SCLC.
2. Any chemotherapy, immunotherapy, biologic, investigational, or hormonal therapy for cancer treatment (except for adjuvant hormonal therapy for breast cancer or prostate cancer defined as M0 disease or prostate-specific antigen [PSA] persistence/recurrence without metastatic disease) within 3 weeks prior to the first dose of trilaciclib/placebo.
3. Any radiotherapy within 2 weeks prior to the first dose of trilaciclib/placebo.
4. Presence of brain metastases/leptomeningeal disease requiring immediate treatment with radiation therapy or steroids. Patient must be off steroids administered for brain metastases for at least 2 weeks prior to the first dose of study drugs.
5. History of ILD/pneumonitis.
6. History of other malignancies, except for curatively treated solid tumors with no evidence of disease for ≥2 years or other non-clinically significant cancers (e.g., basal or squamous cell carcinoma of the skin, in situ carcinoma of the uterine cervix) which may be considered after discussion with the Medical Monitor.
7. Clinically significant (i.e., active) cardiovascular disease at the time of signing the informed consent; for example cerebrovascular accidents (≤ 6 months before the first dose of trilaciclib/placebo), myocardial infarction (≤ 6 months before the first dose of trilaciclib/placebo), unstable angina, serious cardiac arrythmia requiring medication, or uncontrolled symptomatic congestive heart failure [Class II or higher as defined by the New York Heart Association [NYHA] functional classification system])
8. QT corrected using Fridericia’s formula (QTcF) interval >480 msec at screening (confirmed on repeat). For patients with ventricular pacemakers, QTcF >500 msec
9. Known serious active infection including but not limited to, human immunodeficiency virus (HIV) (e.g., viral load indicative of HIV, HIV 1/2 antibodies), Hepatitis B (e.g., Hepatitis B surface antigen reactive or Hepatitis B DNA detected), Hepatitis C (e.g., Hepatitis C ribonucleic acid [quantitative] is detected) or tuberculosis.
10. Other uncontrolled serious chronic disease or psychiatric condition that in the Investigator’s opinion could affect patient safety, compliance, or follow-up in the protocol
11. Known hypersensitivity or allergy to study drugs or any component in their formulations
12. Pregnant or lactating women. Women of childbearing potential must have negative serum pregnancy test result within 7 days prior to initiating study treatment
13. Patients who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the Investigator, or patients who are employees of G1 Therapeutics, Inc. directly involved in the conduct of the study
14. Concurrent participation in any other interventional clinical trial
15. Receipt of a live, attenuated vaccine within 30 days prior to the first dose of study drugs or anticipation that such a live, attenuated vaccine will be required during the study treatment period. Inactive vaccines, including but not limited to influenza vaccine, pneumococcal vaccine, shingles vaccine, and regionally approved Covid-19 vaccines are allowed.
16. Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. OS is defined as time from randomization to death due to any cause for those who died; or time to last contact known as alive for those who survived in the study (censored cases)

Secondary endpoints 22

1. PFS is defined as time from randomization to disease progression using RECIST v1.1 or death due to any cause, whichever occurs first; for patients without disease progression or death, PFS will be calculated per censoring rules
2. ORR, as defined as the proportion of patients with confirmed CR and PR per RECIST v1.1
3. Duration of objective response per RECIST v1.1
4. Duration of severe (Grade 4) neutropenia in Cycle 1
5. Occurrence of severe (Grade 4) neutropenia
6. Occurrence of febrile neutropenia AEs
7. Occurrence of G-CSF administration
8. Occurrence of Grade 3 or 4 decreased hemoglobin laboratory values
9. RBC transfusions on or after Week 5 (occurrence and number of transfusions)
10. Occurrence of ESA administration
11. Occurrence of Grade 3 or 4 decreased platelet count laboratory values
12. Platelet transfusions (occurrence and number of transfusions)
13. Occurrence and number of hospitalizations due to chemotherapy-induced myelosuppression
14. All-cause dose reductions (occurrence and number of reductions)
15. All-cause cycle delays (occurrence and number of delays)
16. Occurrence and severity of AEs by NCI CTCAE v5.0
17. Occurrence of study treatment discontinuation due to AEs
18. Occurrence of Trilaciclib AESIs
19. Occurrence of Grade 3 or 4 abnormalities in serum chemistry laboratory parameters
20. Occurrence of trilaciclib infusion interruptions
21. Occurrence of topotecan infusion interruptions
22. Relative dose intensity of topotecan

Investigational products

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

Test 1

Placebo 3

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Pharmacosmos A/S

Sponsor organisation

Pharmacosmos A/S

Address

Roervangsvej 30

City

Holbaek

Postcode

4300

Country

Denmark

Scientific contact point

Organisation

Pharmacosmos A/S

Contact name

Lars Lykke Thomsen

Public contact point

Organisation

Pharmacosmos A/S

Contact name

Amalie Bjerre Jørgensen

Third parties 4

Locations

8 EU/EEA countries · 38 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 142 files

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

Application history

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