Trilaciclib, a CDK 4/6 Inhibitor, in Patients Receiving Docetaxel for Metastatic Non-Small Cell Lung Cancer (NSCLC) (PRESERVE 4)
Condition: Metastatic Non-Small Cell Lung Cancer; NSCLC; Lung Cancer
MeSH terms: Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
Intervention: Trilaciclib; Placebo; Docetaxel
Intervention description: Trilaciclib administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.; Placebo administered IV over 30 minutes prior to docetaxel IV on Day 1 of each 21-day cycle.; Docetaxel administered IV on Day 1 of each 21-day cycle.
Intervention MeSH terms: Docetaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Trilaciclib; Lung Cancer; Non-Small Cell Lung Cancer; PRESERVE 4; CDK 4/6 Inhibitor; cyclin-dependent kinase 4/6 inhibitor; Preserve; NSCLC; solid tumors; chemotherapy; metastatic; myeloprotection; advanced; stage 4; lung; docetaxel; COSELA; G1T28

Summary:

      This is a randomized, double-blind, placebo-controlled, global, multicenter, Phase 2 trial
      evaluating the effect of trilaciclib on overall survival when administered prior to docetaxel
      in patients with metastatic NSCLC treated in the 2nd or 3rd line setting.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥18 years of age at the time of signing the informed consent.

          -  Histologically or cytologically confirmed metastatic NSCLC (squamous or nonsquamous)
             with no known actionable driver mutations (eg, EGFR, ROS1, ALK).

               1. Patients must have had documented disease progression during or after 1 or 2
                  lines of systemic treatment for recurrent or metastatic disease.

               2. Two components of treatment must have been received in the same line or as
                  separate lines of therapy: (i) a maximum of 1 line of platinum-containing
                  chemotherapy regimen for recurrent/metastatic disease, and (ii) a maximum of 1
                  line of a locally approved/authorized PD-1/PD-L1 mAb containing regimen for
                  recurrent/metastatic disease.

               3. Maintenance therapy following platinum doublet-based chemotherapy is not
                  considered as a separate line of therapy. Maintenance therapy is defined as
                  therapy given within 42 days after the last dose of platinum-based chemotherapy
                  in patients with ongoing clinical benefit (complete response [CR], partial
                  response [PR] or stable disease [SD]).

          -  Measurable or non-measurable disease per RECIST v1.1.

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2.

          -  A formalin-fixed paraffin-embedded (FFPE) tumor specimen (from archival or fresh
             biopsy) with an associated pathology report documenting NSCLC must be available to
             send to the Sponsor, within the specified timeframe, for planned retrospective
             biomarker analyses.

          -  Adequate organ function defined by the normal laboratory values.

        Exclusion Criteria:

          -  Prior therapy with docetaxel.

          -  Any contraindication to the administration of docetaxel at the discretion of the
             investigator.

          -  Mixed NSCLC/SCLC, or lung tumors whose predominant histology is sarcomatoid, or
             neuroendocrine.

          -  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.

          -  Any radiotherapy within 2 weeks prior to the first dose of trilaciclib/placebo.

          -  Presence of central nervous system (CNS) metastases requiring immediate treatment with
             radiation therapy or steroids (i.e., patient must be off steroids administered for
             brain metastases for at least 14 days prior to the first dose of trilaciclib/placebo).

          -  Presence of leptomeningeal disease.

          -  Significant third-space fluid retention (eg, ascites or pleural effusion) not amenable
             to required repeat drainage.

          -  QT corrected using Fridericia's formula (QTcF) interval >480 msec at screening
             (confirmed on repeat). For patients with ventricular pacemakers, QTcF >500 msec.

          -  Symptomatic peripheral neuropathy.

          -  History of interstitial lung disease (ILD).

          -  Prior allogeneic or autologous hematopoietic stem cell or bone marrow transplantation.