Trilaciclib given before sacituzumab tirumotecan to protect bone marrow in EGFR-mutated advanced NSCLC

A Prospective, Single-arm Phase II Trial of Trilaciclib Administered Prior to Sacituzumab Tirumotecan in Patients With EGFR-mutated, Advanced Non-Small Cell Lung Cancer (NSCLC) Who Have Progressed on Prior EGFR Tyrosine Kinase Inhibitors（PROTECT-2）

This trial will test whether giving trilaciclib before sacituzumab tirumotecan helps protect the blood and reduce blood-related side effects in people with advanced EGFR‑mutated non-small cell lung cancer who have stopped responding to EGFR-TKI therapy.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 49 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: The First Affiliated Hospital of Xiamen University (Academic / other)
• Drugs / interventions: radiation, sacituzumab
• Locations: 1 site (Xiamen, Fujian)
• Trial ID: NCT06992739 on ClinicalTrials.gov

What this trial studies

This is a prospective, single-arm phase II trial enrolling patients with advanced EGFR-mutant NSCLC who have progressed after EGFR-TKI therapy. Participants receive trilaciclib prior to each dose of sacituzumab tirumotecan, and treatment continues until disease progression or intolerable toxicity. The study tracks whole blood counts over time, hematologic toxicities (including febrile neutropenia and infections), transfusion requirements, and need for hematopoietic support. Tumor response is assessed by RECIST 1.1 with baseline imaging within 21 days before starting treatment.

Who should consider this trial

Good fit: Adults aged 18–75 with advanced or metastatic EGFR-mutant NSCLC, ECOG 0–1, expected survival ≥3 months, and progression after third-generation EGFR-TKI (or appropriate prior EGFR-TKI sequencing per protocol) are eligible.

Not a fit: Patients with poor performance status (ECOG >1), life expectancy under three months, uncontrolled comorbidities, or earlier-stage disease are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, the approach could reduce chemotherapy-related bone marrow damage, lower transfusion and infection rates, and make sacituzumab tirumotecan better tolerated.

How similar studies have performed: Trilaciclib has shown myeloprotective effects in other tumor types and chemotherapy regimens, and sacituzumab tirumotecan has demonstrated activity in Trop-2–expressing tumors, but their combination in EGFR-mutant NSCLC after TKI failure is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. Age range: 18-75 years old; No gender restrictions;
2. ECOG PS score 0-1;
3. Expected survival time ≥ 3 months;
4. Patients with locally advanced or metastatic EGFR mutant non-small cell lung cancer diagnosed by histological or cytological examination, who have failed third-generation EGFR-TKI treatment and have experienced up to second-line EGFR-TKI treatment failure;

   1. Patients who have only progressed with 1-2 generations of EGFR-TKI treatment need to undergo third-generation EGFR-TKI treatment;
   2. If patients receive third-generation EGFR-TKI during neoadjuvant and/or postoperative adjuvant therapy and progress to metastatic or locally advanced disease more than 6 months after the last dose, they need to receive third-generation EGFR-TKI treatment again before they can participate in this study;
   3. If patients receive third-generation EGFR-TKI during neoadjuvant and/or postoperative adjuvant therapy and progress to metastatic or locally advanced disease within 6 months after the last dose, they can directly participate in this study;
   4. Imaging disease progression was recorded during or after the recent first-line treatment process.
5. There must be at least one measurable lesion that meets the RECIST 1.1 criteria;
6. The main organ functions well and meets the following standards:

   Blood routine examination (without blood transfusion or correction with hematopoietic stimulating factor drugs within 14 days): hemoglobin (Hb) ≥ 90g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count (PLT) ≥ 80 × 109/L; Biochemical examination: alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN (≤ 5 × ULN for patients with liver metastasis); Serum total bilirubin (TBIL) ≤ 1.5 × ULN (Gilbert syndrome subjects, ≤ 3×ULN）； Serum creatinine (Cr) ≤ 1.5 × ULN, or creatinine clearance rate ≥ 60mL/min; Coagulation function: activated partial thromboplastin time (APTT), international normalized ratio (INR), prothrombin time (PT) ≤ 1.5 × ULN;
7. The subject must recover from all toxic reactions (except hair loss) of previous treatment to ≤ level 1 (evaluated based on CTCAE 5.0 criteria);
8. Women: All women with potential fertility must have a negative serum pregnancy test result during the screening period, and must take reliable contraceptive measures from signing the informed consent form until 3 months after the last dose;
9. Participants voluntarily participate in this study, understand and sign the informed consent form.

Exclusion Criteria:

1. History of myeloid leukemia, myelodysplastic syndrome, or accompanying sickle cell disease;
2. Symptomatic CNS metastases and/or leptomeningeal diseases that require immediate radiotherapy or steroid treatment;
3. Have undergone surgery or radiation therapy within 4 weeks prior to the administration of the first dose of the study drug;
4. Clinical symptoms or diseases of the heart that have not been well controlled, such as: (1) NYHA grade 2 or above heart failure; (2) Unstable angina pectoris; (3) Have experienced myocardial infarction within 6 months; (4) Patients with clinically significant supraventricular or ventricular arrhythmias that require treatment or intervention;
5. History of interstitial lung disease, slow progressive dyspnea and dry cough, sarcoidosis, silicosis, idiopathic pulmonary fibrosis, pulmonary allergic pneumonia, or multiple allergic or peripheral arterial diseases (such as claudication, Leo Buerger's disease).
6. Patients who have received hematopoietic stem cell or bone marrow transplantation in the past;
7. Patients who need to receive radiation therapy at the same time;
8. Those who are known to have a history of allergies to the components of this drug regimen;
9. Pregnant or lactating women;
10. The researcher believes that the patient is not suitable to participate in any other circumstances of this study.

Where this trial is running

Xiamen, Fujian

• The First Affiliated Hospital of Xiamen University — Xiamen, Fujian, China (Recruiting)

Conditions NSCLC; EGFR; Myelosuppression