Lung AdenocarcinomaPhase 2NCT07878871
Firmonertinib Plus Chemotherapy for Unresectable EGFR PACC-Mutant Stage III Lung Cancer: A Phase II Study
A Phase 2 study testing Firmonertinib and Platinum-based chemotherapy in people with Lung Adenocarcinoma and Stage III Lung Cancer, run by Hunan Province Tumor Hospital at 1 site in China.
Trial summary
This is a prospective, single-arm, multicenter Phase II clinical study. It aims to evaluate the efficacy and safety of Firmonertinib combined with chemotherapy in patients with unresectable Stage III lung adenocarcinoma harboring EGFR PACC mutations. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Lung Adenocarcinoma, Stage III Lung Cancer, EGFR Positive Non-small Cell Lung Cancer
- What is being tested?
- Firmonertinib and Platinum-based chemotherapy
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- Nov 2026to Dec 2031
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed locally advanced (Stage IIIA-IIIC according to the AJCC 9th edition) lung adenocarcinoma that is assessed by the investigator as unresectable or unsuitable for surgical resection.
- Confirmed presence of EGFR PACC mutations by genetic testing at a tertiary Grade A hospital.
- No prior local or systemic anti-tumor therapy for Stage III non-small cell lung cancer, including standard chemotherapy, biological therapy, targeted therapy, immunotherapy, or investigational therapy.
- According to RECIST 1.1 criteria, at least one measurable lesion that has not been previously irradiated and has not undergone tissue biopsy during the screening period.
- Fully understands the study and voluntarily signs the Informed Consent Form (ICF).
- Age ≥ 18 years, both genders.
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- Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1, with no deterioration within 2 weeks prior to enrollment.
- Life expectancy ≥ 12 weeks.
- Adequate organ function:
- Hematology: Absolute neutrophil count (ANC) ≥ 1500/µL; Platelet count ≥ 100×10^9/L; Hemoglobin ≥ 9.0 g/dL.
- Renal: Serum creatinine ≤ 1.5 × ULN, or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).
- Hepatic: Total bilirubin ≤ 1.5 × ULN, or direct bilirubin within normal limits for subjects with total bilirubin > 1.5 × ULN; AST (SGOT) and ALT (SGPT) ≤ 2.5 × ULN.
- Coagulation: International Normalized Ratio (INR) or Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) ≤ 1.5 × ULN. Exception: Subjects receiving anticoagulation therapy must have PT or APTT within the intended therapeutic range of the anticoagulant.
- Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to the first dose. Women of childbearing potential and male subjects with partners of childbearing potential must agree to use highly effective contraception during the study and for 180 days after the last dose of study treatment.
Who cannot join
- Subjects meeting any of the following exclusion criteria cannot be enrolled in this study:
- Pathological type of squamous cell carcinoma or small cell lung cancer.
- Known history of severe hypersensitivity reactions to the active or inactive excipients of Firmonertinib, or to drugs with a similar structure or class to Firmonertinib.
- Prior systemic anti-tumor therapy for NSCLC, including investigational drug therapy.
- History of (non-infectious) pneumonitis/interstitial lung disease requiring steroids, or current pneumonitis/interstitial lung disease requiring steroid therapy.
- Known active autoimmune disease requiring systemic therapy.
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- Any subject with known or suspected autoimmune disease or immunodeficiency, EXCEPT: Subjects with hypothyroidism who do not require hormone therapy or are receiving stable dose hormone replacement therapy; subjects with Type 1 diabetes mellitus whose blood glucose is stably controlled.
- Uncontrolled active hepatitis B (defined as positive HBsAg at screening AND HBV-DNA level above the upper limit of normal of the testing laboratory at the study center. Exception: Subjects with HBV-DNA < 500 IU/mL within 28 days prior to enrollment, who have received at least 14 days of local standard antiviral therapy, and are willing to continue antiviral therapy during the study may be enrolled); Active hepatitis C (defined as positive hepatitis C virus surface antibody [HCsAb] at screening, with positive HCV-RNA).
- Known human immunodeficiency virus (HIV) infection (known positive HIV antibody).
- Known severe or uncontrolled underlying diseases, including but not limited to hemodynamically unstable cardiovascular events, symptomatic cerebrovascular events, or cirrhosis of Child-Pugh Grade A or higher within 6 months.
- Any history or current evidence of diseases, treatments, or laboratory abnormalities that, in the investigator's judgment, may confound the trial results, interfere with the subject's participation in the full trial, or are not in the best interest of the subject.
- Other malignancies other than non-small cell lung cancer within 5 years prior to the first dose. Malignancies with negligible risk of metastasis or death (e.g., expected disease-free survival > 5 years) and expected to achieve curative outcomes after treatment (e.g., adequately treated carcinoma in situ of the cervix, basal cell or squamous cell skin cancer, radically resected ductal carcinoma in situ) may be exempted.
- Pregnancy or lactation.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Hunan Cancer Hospital
Changsha, Hunan, 410013
Yongchang Zhang, MD, PhD, +86 073189762765, zhangyongchang@hnca.org.cn
Liang Zeng, MD, PhD, +86 073189762765, zengliang@hnca.org.cn
About this study
Official title: Firmonertinib Combined With Chemotherapy for Unresectable EGFR PACC-Mutant Stage III Lung Adenocarcinoma: A Prospective, Single-Arm, Multicenter Phase II Clinical Study
This is a prospective, single-arm, multicenter Phase II clinical study. It aims to evaluate the efficacy and safety of Firmonertinib combined with chemotherapy in patients with unresectable Stage III lung adenocarcinoma harboring EGFR PACC mutations. Participants will receive Firmonertinib combined with standard chemotherapy. The primary objective is to assess the objective response rate (ORR). This study will provide important evidence for a potential new treatment option for this specific patient population.
Read the detailed description
Background: EGFR PACC mutations (P-loop and αC-helix compressing mutations) represent a distinct subtype of EGFR mutations with unique structural characteristics and potentially different responses to targeted therapies. There is an unmet clinical need for effective treatment regimens for patients with unresectable Stage III lung adenocarcinoma harboring these mutations. Firmonertinib is a highly selective third-generation EGFR-TKI with demonstrated efficacy. Combining targeted therapy with chemotherapy may provide synergistic anti-tumor effects.
Study Design: This is a prospective, single-arm, multicenter Phase II clinical study. Eligible patients will receive Firmonertinib in combination with chemotherapy.
Objectives: The primary objective of this study is to evaluate the objective response rate (ORR) of Firmonertinib combined with chemotherapy in this patient population. The secondary objectives include: To evaluate the 1-year and 3-year event-free survival (EFS) rates, surgical conversion rate, R0 resection rate, major pathological response (MPR), pathological complete response (pCR), event-free survival (EFS), and overall survival (OS).To assess the safety and tolerability of the combination regimen.
Significance: This study aims to provide robust clinical evidence for the efficacy and safety of Firmonertinib combined with chemotherapy, potentially establishing a new therapeutic option for patients with unresectable EGFR PACC-mutant Stage III lung adenocarcinoma.
- Being tested
- Firmonertinib, Platinum-based chemotherapy
- Keywords
- Firmonertinib, EGFR PACC mutation, Unresectable Stage III, Lung Adenocarcinoma
- Medical subject headings
- Adenocarcinoma of Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FirmonertinibDrug
Firmonertinib mesylate tablets, 160 mg, oral administration, once daily. Administered during induction and consolidation phases.
Platinum-based chemotherapyDrug
Pemetrexed (500 mg/m²) combined with Carboplatin or Cisplatin. Administered during the 3-4 cycles of induction therapy
| Study group | Role | What they receive |
|---|---|---|
| Firmonertinib Combined with Chemotherapy | Experimental | Participants will receive induction therapy consisting of Firmonertinib (160 mg orally once daily, continuously) combined with platinum-based chemotherapy (Pemetrexed 500 mg/m² plus Carboplatin or Cisplatin) for 3-4 cycles. Following induction, an MDT assessment will determine subsequent treatment (surgery, radiotherapy, or other therapies). Patients confirmed for adjuvant/consolidation will receive Firmonertinib (160 mg orally once daily) for up to 3 years. Receives: Drug: Firmonertinib; Drug: Platinum-based chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate (ORR)
Proportion of participants achieving complete response (CR) or partial response (PR) as assessed by investigators according to RECIST v1.1 criteria
Measured: From baseline to the end of study treatment (up to approximately 36 months)
Secondary outcomes (7)
1-year and 3-year Event-Free Survival (EFS) Rate
Proportion of participants who are event-free at 1 year and 3 years from enrollment. Events are defined as disease progression, relapse, or death from any cause
Measured: At 1 year and 3 years post-enrollment
Surgical Conversion Rate
Proportion of participants with unresectable disease at baseline who achieve resectability and undergo surgery after induction therapy
Measured: After 3-4 cycles of induction therapy (up to approximately 6 months)
R0 Resection Rate
Proportion of participants who undergo surgical resection with microscopically negative margins (R0 resection)
Measured: At the time of surgery (up to approximately 6 months)
Major Pathological Response (MPR) and Pathological Complete Response (pCR) Rate
Proportion of participants achieving MPR (≤10% viable tumor cells) or pCR (no viable tumor cells) in resected specimens
Measured: At the time of surgery (up to approximately 6 months)
Event-Free Survival (EFS)
Time from enrollment to the first occurrence of disease progression, relapse, or death from any cause
Measured: From enrollment to the end of study (up to approximately 36 months)
Overall Survival (OS)
Time from enrollment to death from any cause
Measured: From enrollment to the end of study (up to approximately 36 months)
Safety and Tolerability
Incidence, severity, and relatedness of adverse events (AEs) and serious adverse events (SAEs) according to NCI-CTCAE v5.0
Measured: From first dose to 30 days after the last dose of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Oct 2026
- Study startNov 2026 (estimated)
- Primary completionDec 2031 (estimated)
- Study completionDec 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Lung AdenocarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective, single-arm, multicenter Phase II clinical study. All enrolled participants will receive Firmonertinib combined with standard chemotherapy. There is no randomization or control group in this study.
- Masking
- None (open label)
- Enrolment
- 27 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hunan Province Tumor Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Yongchang Zhang, Hunan Province Tumor Hospital
- Investigators
- Yongchang Zhang, MD, PhD, Principal investigator, Hunan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07878871
- Sponsor's protocol ID
- IIT331
- Status last verified
- Oct 2026
- First submitted
- 10 Oct 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data will not be shared because the informed consent forms signed by the participants do not permit the public sharing of individual data. Additionally, local ethical and regulatory requirements regarding patient privacy protection restrict the sharing of individual data outside the study team