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NCT05112536

Trilaciclib, a CDK4/6 Inhibitor, in Patients With Early-Stage Triple Negative Breast Cancer

Completed Phase 2 Results posted Last updated 12 March 2024
What this trial tests

Phase 2 trial testing Trilaciclib in Triple Negative Breast Cancer in 24 participants. Completed in 13 March 2023.

Timeline
3 March 2022
Primary endpoint
31 October 2022
13 March 2023

Quick facts

Lead sponsorG1 Therapeutics, Inc.
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment24
Start date3 March 2022
Primary completion31 October 2022
Estimated completion13 March 2023
Sites7 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

G1 Therapeutics, Inc. — full company profile →

Who can join

18 and older, female only, with Triple Negative Breast Cancer or Breast Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Immune-based Mechanism of Action Primary · Up to 8 days after lead-in trilaciclib dose

Evaluated 7 days after a single-dose of trilaciclib, measured by the change in CD8+ T cells/regulatory T cells (Treg) ratio in tumor tissue; post-trilaciclib ratio minus pre-trilaciclib ratio. Research shows a correlation between immune cells, (tumor-infiltrating lymphocytes - TILs), and favorable outcomes. Both the presence of effector CD8+ T cells and the ratio of effector CD8+ T cells to immune-suppressive regulatory T cells (Treg) correlate with improved outcome and long-term survival in solid cancers. Therefore, the higher the ratio of CD8+ T cells/Tregs, the better the predicted outcome

GroupValue95% CI
Trilaciclib Plus Chemotherapy0.3-0.5 – 2.7
Pathologic Complete Response (pCR) Rate Secondary · Up to 26 weeks

Rate of pCR using the definition of ypT0/Tis ypN0 (i.e., no invasive residual tumor in breast or nodes; noninvasive breast residuals allowed) as assessed by the local pathologist.

Achieved pCR
GroupValue95% CI
Trilaciclib Plus Chemotherapy10
Did not achieve pCR
GroupValue95% CI
Trilaciclib Plus Chemotherapy14
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability) Secondary · Up to 28 weeks

Safety/tolerability as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

Adverse Events CTCAE grade >/= 3
GroupValue95% CI
Trilaciclib Plus Chemotherapy15
Adverse Events CTCAE grade >/= 4
GroupValue95% CI
Trilaciclib Plus Chemotherapy5
Study drug related adverse event
GroupValue95% CI
Trilaciclib Plus Chemotherapy24
Study drug related serious adverse event
GroupValue95% CI
Trilaciclib Plus Chemotherapy2
Trilaciclib-related adverse event leading to discontinuation
GroupValue95% CI
Trilaciclib Plus Chemotherapy0
Adverse event leading to death
GroupValue95% CI
Trilaciclib Plus Chemotherapy0
Trilaciclib adverse events of special interest (AESI)
GroupValue95% CI
Trilaciclib Plus Chemotherapy10

Adverse events — posted to ClinicalTrials.gov

Time frame: 28 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Trilaciclib Plus Chemotherapy
Serious: 4/24 (17%)
Deaths: 0/24

Serious adverse events (14 terms)

ReactionSystemTrilaciclib Plus Chemother…
Pulmonary embolismRespiratory, thoracic and mediastinal disorders
Abscess limbInfections and infestations
COVID-19Infections and infestations
Herpes simplex encephalitisInfections and infestations
PneumoniaInfections and infestations
SepsisInfections and infestations
UrosepsisInfections and infestations
Pulmonary fibrosisRespiratory, thoracic and mediastinal disorders
Deep vein thrombosisVascular disorders
Orthostatic hypotensionVascular disorders
Febrile neutropeniaBlood and lymphatic system disorders
ColitisGastrointestinal disorders
Physical deconditioningGeneral disorders
HypertransaminasaemiaHepatobiliary disorders
Other adverse events (161 terms — click to expand)

ReactionSystemTrilaciclib Plus Chemother…
FatigueGeneral disorders
NauseaGastrointestinal disorders
AlopeciaSkin and subcutaneous tissue disorders
HeadacheNervous system disorders
ConstipationGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Neuropathy peripheralNervous system disorders
StomatitisGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
DysgeusiaNervous system disorders
Bone painMusculoskeletal and connective tissue disorders
InsomniaPsychiatric disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
Dry mouthGastrointestinal disorders
PruritisSkin and subcutaneous tissue disorders
DizzinessNervous system disorders
Decreased appetiteMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
AnxietyPsychiatric disorders
RashSkin and subcutaneous tissue disorders
Oral herpesInfections and infestations
ArthralgiaMusculoskeletal and connective tissue disorders
MyalgiaMusculoskeletal and connective tissue disorders
Platelet count decreasedInvestigations
Procedural painInjury, poisoning and procedural complications
DyspepsiaGastrointestinal disorders
Gastrooesophageal reflux diseaseGastrointestinal disorders
Oedema peripheralGeneral disorders
PyrexiaGeneral disorders
Nail discolourationSkin and subcutaneous tissue disorders
Nail disorderSkin and subcutaneous tissue disorders
Urinary tract infectionInfections and infestations
Back painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
HypokalemiaMetabolism and nutrition disorders
Hot flushVascular disorders
Catheter site painGeneral disorders
OedemaGeneral disorders

Most-reported serious reactions: Pulmonary embolism, Abscess limb, COVID-19, Herpes simplex encephalitis, Pneumonia, Sepsis, Urosepsis, Pulmonary fibrosis.

Data from ClinicalTrials.gov NCT05112536 adverse events section.

Sponsor's own description

The purpose of this study is to evaluate the mechanism of action, as well as the safety and efficacy of trilaciclib in combination with standard of care treatment in the neoadjuvant setting of early-stage triple negative breast cancer (TNBC). This study will have four phases: 1) Screening Phase, 2) Trilaciclib Lead-In Phase, 3) Treatment Phase, and 4) Surgery and Follow-Up Phase. After a screening phase of up to 21 day, each participant will receive trilaciclib single-dose monotherapy during the lead-in phase, followed by a tumor biopsy. During the treatment phase, each participant will receive trilaciclib with standard of care chemotherapy. Immunotherapy may be included during the treatment phase, per standard of care. 3-5 weeks following conclusion of the treatment phase, each participant will undergo definitive surgery. A 30-day Safety Follow-up Visit will occur 30 days after the last dose of trilaciclib and an End of Study Visit will occur within 14 days after definitive surgery.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Recent advances in targeted strategies for triple-negative breast cancer.
    Zhu S, Wu Y, Song B, Yi M, et al · · 2023 · cited 200× · PMID 37641116 · DOI 10.1186/s13045-023-01497-3
  2. Immunotherapy Targeting PD-1/PD-L1 in Early-Stage Triple-Negative Breast Cancer.
    Yang T, Li W, Huang T, Zhou J. · · 2023 · cited 24× · PMID 36983708 · DOI 10.3390/jpm13030526
  3. Modern Immunotherapy in the Treatment of Triple-Negative Breast Cancer.
    Wesolowski J, Tankiewicz-Kwedlo A, Pawlak D. · · 2022 · cited 20× · PMID 36010854 · DOI 10.3390/cancers14163860
  4. Immune Checkpoint Blockades in Triple-Negative Breast Cancer: Current State and Molecular Mechanisms of Resistance.
    Kim H, Choi JM, Lee KM. · · 2022 · cited 18× · PMID 35625867 · DOI 10.3390/biomedicines10051130
  5. Improving efficacy of TNBC immunotherapy: based on analysis and subtyping of immune microenvironment.
    Yang Y, Li H, Yang W, Shi Y. · · 2024 · cited 11× · PMID 39430759 · DOI 10.3389/fimmu.2024.1441667
  6. Evolving treatment landscape of immunotherapy in breast cancer: current issues and future perspectives.
    Valenza C, Rizzo G, Passalacqua MI, Boldrini L, et al · · 2023 · cited 10× · PMID 36743524 · DOI 10.1177/17588359221146129
  7. Investigating potential immune mechanisms of trilaciclib administered prior to chemotherapy in patients with metastatic triple-negative breast cancer.
    Tan AR, O'Shaughnessy J, Cao S, Ahn S, et al · · 2023 · cited 3× · PMID 37418031 · DOI 10.1007/s10549-023-07009-8
  8. CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.
    Blume J, Claus L, Isermann T, Dickmanns A, et al · · 2023 · cited 2× · PMID 37266562 · DOI 10.1080/15384101.2023.2217003

Verify or expand the search:

Other trials of Trilaciclib

Trials testing the same drug.

Other recruiting trials for Triple Negative Breast Cancer

Currently open trials in the same condition.

Other G1 Therapeutics, Inc. trials

Trials by the same sponsor.

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