Not yet recruitingNCT07885709Updated Oct 21, 2026

MRD and Imaging Guided Adaptive Neoadjuvant Therapy for Resectable NSCLC

A Phase 2 interventional study of PD-1 inhibitor and Carboplatin in Non-Small Cell Lung Cancer (NSCLC), sponsored by Peking University People's Hospital. Not yet recruiting at 1 site in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-21.

Sponsored by Peking University People's Hospital · Phase 2, Interventional, and Treatment

Updated Oct 21, 2026Newly registeredGo to Updates ↓

Phase: Phase 2
Study type: Interventional
Enrollment: 100
Allocation: Not applicable
Ages: 18 Years and older
Sex: All

Study summary

Neoadjuvant immunotherapy combined with platinum-based doublet chemotherapy has been established as the standard of care for driver-gene-negative (EGFR/ALK wild-type) stage II-IIIB non-small cell lung cancer (NSCLC), yielding pathological complete response (pCR) rates of 30-40%. Nevertheless, a substantial proportion of patients (approximately 60-70%) do not attain pCR, and strategies to further augment the pCR rate through treatment escalation remain an unmet clinical need. Accumulating evidence indicates that failure of ctDNA clearance and radiological stable disease (SD) following two cycles of neoadjuvant therapy are each robust predictors of unfavorable pathological response, and their combined assessment may enable accurate identification of the patient subset least likely to derive benefit from immunotherapy.

This single-arm, proof-of-concept study will enroll patients with resectable or borderline resectable, EGFR/ALK wild-type, stage II-IIIB (N2) NSCLC. All participants will initially receive two cycles of a PD-1 inhibitor (nivolumab, pembrolizumab, toripalimab, or tislelizumab) in combination with platinum-based doublet chemotherapy. Following two cycles, patients will undergo ctDNA-MRD assessment and radiological evaluation. Patients in whom ctDNA has not cleared and whose radiological response is stable disease will be assigned to the treatment-escalation group and receive an intensified regimen comprising a PD-1 inhibitor plus anlotinib plus chemotherapy for cycles 3-4, whereas all remaining patients will continue the original regimen. Upon completion of neoadjuvant therapy, patients deemed resectable by a multidisciplinary team (MDT) will proceed to definitive surgery.

The primary endpoint is the pCR rate in the treatment-escalation population. This study seeks to establish a precision escalation strategy guided by ctDNA-MRD in conjunction with imaging response, thereby providing an effective therapeutic approach for patients with NSCLC who respond poorly to immunotherapy and informing the design of subsequent confirmatory trials.

Conditions studied

Non-Small Cell Lung Cancer (NSCLC)

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Keywords

Non-Small Cell Lung Cancer(NSCLC)
ctDNA
minimal residual disease (MRD)
neoadjuvant immunotherapy

In context

Carcinoma, Non-Small-Cell Lung

6,641 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,665 are open to participants now.

This study's planned enrollment of 100 is above the median of 62 across 5,327 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.

Browse Carcinoma, Non-Small-Cell Lung studies →

Lead sponsor

Peking University People's Hospital is the lead sponsor of 603 studies on the registry; 241 are open to participants now.

Browse Peking University People's Hospital studies →

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

Voluntary participation with signed informed consent.
Previously untreated, histologically confirmed, resectable or borderline resectable stage II-IIIA or IIIB (N2) non-small cell lung cancer, per the 8th edition AJCC staging.
Negative for EGFR and ALK driver alterations, confirmed by next-generation sequencing (NGS) or RT-PCR on tumor tissue; blood-based NGS permitted when tissue is insufficient.
Sufficient tumor tissue for PD-L1 immunohistochemistry and NGS testing, with baseline tissue reserved for construction of a tumor-informed, fixed panel for subsequent MRD detection.
Age ≥18 years, either sex.
Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
Adequate cardiac function with left ventricular ejection fraction (LVEF) >50%.
Adequate pulmonary function (FEV1 >1.5 L and DLCO >50%) to tolerate definitive lung cancer resection.
Adequate bone marrow function: white blood cell count >4×10⁹/L, neutrophil count >1.5×10⁹/L, hemoglobin >10 g/dL, and platelet count >100×10⁹/L.
Adequate renal function with glomerular filtration rate >60 mL/min.
Adequate hepatic function: total bilirubin \<1.5× upper limit of normal (ULN), aspartate aminotransferase (AST) \<3× ULN, and alanine aminotransferase (ALT) \<3× ULN.
Presence of at least one measurable lesion per RECIST 1.1.
Women of childbearing potential must have a negative serum pregnancy test within 3 days prior to enrollment and agree to use effective contraception during study treatment and for 120 days after the last dose. Women of childbearing potential are defined as sexually mature women who (1) have not undergone hysterectomy or bilateral oophorectomy and (2) have not been naturally postmenopausal for 12 consecutive months (cancer-therapy-related amenorrhea does not preclude childbearing potential).

Exclusion criteria

Exclusion Criteria:

Active autoimmune disease or a history of autoimmune disease that may recur, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, autoimmune thyroid disease (adequately controlled hypothyroidism on stable hormone replacement may be permitted), type 1 diabetes mellitus, multiple sclerosis, vasculitis, or glomerulonephritis.
Active hepatitis B or C requiring antiviral therapy; patients with hepatitis B must have HBV-DNA \<500 IU/mL and have received at least 14 days of anti-HBV therapy prior to enrollment, with treatment continued during the study; patients with positive HCV RNA are excluded.
Known allergy to carboplatin, paclitaxel, nab-paclitaxel, pemetrexed, or other chemotherapeutic agents.
History of allergy to monoclonal antibody drugs.
Known allergy to anlotinib or any of its excipients.
Prior allogeneic stem cell or solid organ transplantation.
Severe or active infection requiring systemic therapy within 4 weeks prior to enrollment, including but not limited to active pulmonary tuberculosis, bacterial infection requiring intravenous antibiotics, active fungal infection, or known human immunodeficiency virus (HIV) infection (HIV antibody positive).
Psychiatric disorders or any other condition that would preclude compliance with treatment.
Inability or unwillingness to provide signed informed consent.
Severe cardiovascular disease, including but not limited to: myocardial infarction, unstable angina, cerebrovascular accident (cerebral infarction or hemorrhage), or transient ischemic attack within 6 months prior to enrollment; New York Heart Association (NYHA) class ≥2 congestive heart failure; severe arrhythmia requiring medication (e.g., sustained ventricular tachycardia, or atrial fibrillation with rapid ventricular rate poorly controlled by medication); uncontrolled hypertension (systolic ≥150 mmHg and/or diastolic ≥95 mmHg) despite standard antihypertensive treatment; congenital long QT syndrome, or prolonged Fridericia-corrected QT interval (QTcF) on screening (males >450 ms, females >470 ms).
Clinically significant bleeding risk or coagulation abnormality, including: known bleeding diathesis (e.g., hemophilia, von Willebrand disease) or hereditary coagulation disorders; grade ≥2 hemoptysis (single episode ≥2.5 mL) or grade ≥3 bleeding at other sites within 3 months prior to enrollment; clinically significant gastrointestinal bleeding within 4 weeks prior to enrollment; ongoing full-dose anticoagulation (e.g., warfarin, heparins, direct oral anticoagulants) that cannot be suspended or bridged to low-molecular-weight heparin during the study (patients on prophylactic low-dose anticoagulation may be eligible per investigator judgment); use of aspirin (>325 mg/day) or other platelet-inhibiting nonsteroidal anti-inflammatory drugs (NSAIDs) within 10 days prior to enrollment; imaging showing tumor invasion of or proximity to a major vessel with investigator-assessed bleeding risk.
Major surgery within 4 weeks prior to enrollment (excluding minimally invasive diagnostic procedures such as diagnostic biopsy, percutaneous lung puncture, EBUS-TBNA, or central venous catheterization), or presence of an unhealed surgical incision, ulcer, or fracture.
Pregnancy or breastfeeding.
Prior or concurrent other malignancy (cured low-risk tumors such as basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, or papillary thyroid carcinoma may be enrolled if, per investigator judgment, they do not affect efficacy or safety evaluation).
Known active or uncontrolled interstitial lung disease (ILD) or pulmonary fibrosis, or screening imaging suggestive of ILD/non-infectious pneumonitis requiring corticosteroids, or a history of ILD/non-infectious pneumonitis requiring corticosteroid treatment.
Receipt of a live or live-attenuated vaccine within 30 days prior to enrollment.
Any comorbidity or other condition that, in the investigator's judgment, may affect protocol compliance or render the patient unsuitable for participation.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrollment: 100 participants (estimated)

Study arms

Experimental
ctDNA-MRD and imaging-guided dynamic neoadjuvant therapy
All participants initially receive two 21-day cycles of one PD-1 inhibitor (nivolumab, pembrolizumab, toripalimab, or tislelizumab) plus platinum-based doublet chemotherapy (nab-paclitaxel/carboplatin for squamous; pemetrexed/carboplatin for non-squamous histology). After two cycles, ctDNA-MRD testing and radiological assessment (RECIST 1.1) guide treatment: patients with ctDNA non-clearance and stable disease receive an intensified four-drug regimen (PD-1 inhibitor + anlotinib + nab-paclitaxel + carboplatin) for cycles 3-4, non-squamous patients switching from pemetrexed to nab-paclitaxel; all others (ctDNA clearance, or CR/PR) continue the original regimen. Upon completion of neoadjuvant therapy, patients deemed resectable by a multidisciplinary team undergo definitive surgery.
Drug: PD-1 inhibitor · Drug: Carboplatin · Drug: Nab-paclitaxel · Drug: Pemetrexed · Drug: Anlotinib

Interventions

DrugPD-1 inhibitor
One of four PD-1 inhibitors selected per patient: nivolumab 360 mg, pembrolizumab 200 mg, toripalimab 240 mg, or tislelizumab 200 mg, administered by intravenous infusion once every 3 weeks
Also known as: Nivolumab (Opdivo), Pembrolizumab (Keytruda), Toripalimab (Tuoyi), Tislelizumab (Tevimbra)
DrugCarboplatin
AUC 5 by intravenous infusion on day 1 of each 21-day cycle
DrugNab-paclitaxel
100 mg/m² by intravenous infusion on days 1 and 5 of each 21-day cycle. Used for squamous histology throughout all cycles, and for non-squamous histology in the treatment-escalation group (cycles 3-4), where it replaces pemetrexed
DrugPemetrexed
500 mg/m² by intravenous infusion on day 1 of each 21-day cycle (non-squamous histology). In the treatment-escalation group, pemetrexed is replaced by nab-paclitaxel during cycles 3-4
DrugAnlotinib
12 mg orally once daily on days 1-14 of each 21-day cycle; added during cycles 3-4 in the treatment-escalation group

What researchers measure

Primary outcomes

Pathological complete response (pCR) rate in the treatment-escalation population
pCR is defined as the absence of residual viable tumor cells in the primary lung tumor and all sampled regional lymph nodes upon systematic pathological review of the surgical specimen, per the IASLC 2020 pathological evaluation criteria. The treatment-escalation population comprises patients with ctDNA non-clearance and radiological stable disease (SD) after two cycles of neoadjuvant therapy.
Time frame: At the time of definitive surgery, approximately 13 to 18 weeks after initiation of neoadjuvant therapy

Secondary outcomes

Major pathological response (MPR) rate in the treatment-escalation population
MPR is defined as ≤10% residual viable tumor cells in the primary lung tumor and regional lymph nodes upon pathological review of the surgical specimen; carcinoma in situ is excluded from the MPR calculation. The treatment-escalation population comprises patients with ctDNA non-clearance and radiological stable disease (SD) after two cycles of neoadjuvant therapy.
Time frame: At the time of definitive surgery, approximately 13 to 18 weeks after initiation of neoadjuvant therapy
Pathological complete response (pCR) rate in the intention-to-treat (ITT) population
pCR is defined as the absence of residual viable tumor cells in the primary lung tumor and all sampled regional lymph nodes upon systematic pathological review of the surgical specimen, per the IASLC 2020 pathological evaluation criteria. The ITT population comprises all enrolled patients.
Time frame: At the time of definitive surgery, approximately 13 to 18 weeks after initiation of neoadjuvant therapy
Major pathological response (MPR) rate in the intention-to-treat (ITT) population
MPR is defined as ≤10% residual viable tumor cells in the primary lung tumor and regional lymph nodes upon pathological review of the surgical specimen; carcinoma in situ is excluded from the MPR calculation. The ITT population comprises all enrolled patients.
Time frame: At the time of definitive surgery, approximately 13 to 18 weeks after initiation of neoadjuvant therapy
2-year event-free survival (EFS) rate in the treatment-escalation and ITT populations
EFS is defined as the time from initiation of neoadjuvant therapy to the first occurrence of any of the following, whichever occurs first: radiological disease progression per RECIST 1.1 precluding surgery, local or distant recurrence, or death from any cause
Time frame: 2 years
2-year overall survival (OS) rate in the treatment-escalation and ITT populations
OS is defined as the time from initiation of neoadjuvant therapy to death from any cause.
Time frame: 2 years
Objective response rate (ORR) in the treatment-escalation and ITT populations
Assessed per RECIST 1.1. ORR is defined as the proportion of patients achieving complete response (CR) or partial response (PR).
Time frame: After completion of neoadjuvant therapy (3-4 cycles; each cycle is 21 days), before definitive surgery
Disease control rate (DCR) in the treatment-escalation and ITT populations
Assessed per RECIST 1.1. DCR is defined as the proportion of patients achieving complete response (CR), partial response (PR), or stable disease (SD).
Time frame: After completion of neoadjuvant therapy (3-4 cycles; each cycle is 21 days), before definitive surgery
Incidence and severity of treatment-related adverse events (TRAEs)
Adverse events graded and recorded according to NCI-CTCAE version 5.0.
Time frame: From first dose through 90 days after the last dose of study treatment

Other outcomes

ctDNA-MRD clearance rate (proportion of patients with undetectable ctDNA) at each assessment time point
Time frame: At baseline (Cycle 1 Day 1), on Cycle 2 Day 14, and preoperatively on the day of surgery (each cycle is 21 days)
Correlation between ctDNA-MRD status (cleared vs. not cleared) and pathological response (pCR/MPR)
Time frame: At the time of definitive surgery
Correlation between ctDNA-MRD dynamics (time to clearance, rate of decline) and EFS
Time frame: From treatment initiation through follow-up, up to 2 years

Study locations

1 site

Peking University People's Hospital
Beijing, Beijing Municipality 100044, China
- Kezhong Chen · Contact · mdkzchen@163.com · +86 13488752289

References and documents

Individual participant data

Plan to share: No

No publications or documents are linked to this record.

Timeline

1 registry update since Sep 25, 2026

ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Start is estimated for Nov 2026; primary completion for Jan 2029, 26 months later.

Of 678 non-industry phase 2 interventional studies under Carcinoma, Non-Small-Cell Lung, half reached primary completion within 56 months of starting (the median), counting those still running; a quarter within 36 and three quarters within 81. This study's planned 26 months is below that.

Counting every sponsor, half of 970 studies reached it within 48 months; a quarter within 30 and three quarters within 75.

How these figures are worked out, and which studies are left out of them.

Registered: Oct 7, 2026
First posted: Oct 21, 2026
StartEst.: Nov 1, 2026
Primary completionEst.: Jan 1, 2029
CompletionEst.: Aug 1, 2030
Last update: Oct 21, 2026

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

Registered

First appeared on the registry. No changes since

Oct 21, 2026

Show all 1 update

Oct 21, 2026
First appeared on the registry

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT07885709
Lead sponsor: Peking University People's Hospital
Collaborators: BeOne Medicines, Nanjing Shihejiyin Technology, Inc., Chia Tai Tianqing Pharmaceutical Group Co., Ltd.
Responsible party: Chen KeZhong (Chief Physician, Peking University People's Hospital) — Principal investigator
First posted: Oct 21, 2026
Start date: Nov 1, 2026 (estimated)
Primary completion: Jan 1, 2029 (estimated)
Completion: Aug 1, 2030 (estimated)
Last update: Oct 21, 2026

Study contacts

Kezhong Chen

Contact

mdkzchen@163.com

+86 13488752289

Oversight

Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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Studies of the drugs tested here: Carboplatin · Albumin-Bound Paclitaxel · Pemetrexed · Anlotinib

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