Non-small Cell Lung Cancer (NSCLC)Phase 2PROPHETNCT06977074
PROPHET Study: ctDNA-Guided Personalized Induction Immunochemotherapy for NSCLC
A Phase 2 study testing PD-1 inhibitor and Platinum Doublet in people with Non-small Cell Lung Cancer (NSCLC), run by Sun Yat-sen University at 1 site in China.
Trial summary
The goal of this clinical trial is to evaluate the clinical value of ctDNA testing in guiding the optimization of immunochemotherapy cycles during induction treatment for resectable patients with NSCLC. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Non-small Cell Lung Cancer (NSCLC)
- What is being tested?
- PD-1 inhibitor and Platinum Doublet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 83 participants
- Where
- 1 siteChina
- Study dates
- 10 May 2025to 10 May 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically/cytologically confirmed, untreated stage IIA-IIIB NSCLC (IASLC 8th edition).
- Deemed resectable by MDT.
- EGFR/ALK wild-type (non-squamous patients; squamous patients exempt).
- ECOG PS 0-1.
- Adequate organ function (neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb >9 g/dL, Cr ≤1.5×ULN, AST/ALT ≤3×ULN).
- Measurable lesions (RECIST 1.1).
Who cannot join
- Active autoimmune diseases (exceptions: vitiligo, type I diabetes, stable hypothyroidism).
- Systemic corticosteroids (>10 mg prednisone equivalent/day) within 14 days.
- Grade 3-4 interstitial lung disease.
- Concurrent malignancies requiring treatment.
- Prior anti-PD-1/PD-L1/CTLA-4 therapy.
- Active HBV/HCV, HIV/AIDS, or pregnancy.
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, 1 recruiting
- Recruiting
Sun Yat-sen University Cancer Center
Guangzhou, Guangdong, 510060
Ze-Rui Zhao, +86 87343317, zhaozr@sysucc.org.cn
About this study
Official title: Prospective Phase II Proof-of-Concept Trial on Circulating Tumor DNA (ctDNA)-Optimized Induction Immunochemotherapy Cycle Reduction for Resectable Non-Small Cell Lung Cancer
The goal of this clinical trial is to evaluate the clinical value of ctDNA testing in guiding the optimization of immunochemotherapy cycles during induction treatment for resectable patients with NSCLC. The main questions it aims to answer are:
- Does ctDNA clearance indicate pathological complete response?
- Are additional cycles of immunochemotherapy necessary for patients who have ctDNA clearance after initial cycles of treatment? Researchers will use ctDNA dynamics to guide the cycles of induction treatment to see if some patients can avoid excessive cycles of treatment.
Read the detailed description
Advances in precision medicine have highlighted the potential of circulating tumor DNA (ctDNA) detection in NSCLC diagnosis, treatment efficacy monitoring, and prognosis evaluation. Induction immunotherapy combined with chemotherapy is now a standard treatment for patients with resectable NSCLC, but optimizing the number of immunochemotherapy cycles to enhance efficacy and reduce toxicity remains a critical clinical challenge. In this Phase II, proof-of-concept trial, around 83 patients with AJCC stage IIA-IIIB NSCLCs who are deemed resectable by an MDT team will participate to evaluate the potential role of dynamic ctDNA changes in guiding the cycle reduction of induction immunotherapy combined with chemotherapy while maintaining overall efficacy.
Eligible patients will receive 2 cycles (21-day intervals) of PD-1 inhibitor + platinum-based chemotherapy. Subsequent cycles (1-2 additional cycles) are determined by ctDNA status via tumour-agnostic strategies:
- For patients with ctDNA clearance: Randomized (1:1) to surgery or continued therapy.
- For patients with ctDNA persistence: Sequential 1-2 additional cycles. For all patients who are available to undergo surgery, the operation will be performed 4-6 weeks following the last cycle of treatment.
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Being tested
- PD-1 inhibitor, Platinum Doublet
- Keywords
- Non-small cell lung cancer, ctDNA, Induction therapy, Immunochemotherapy
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PD-1 inhibitorDrug
Two to four cycles of tislelizumab at a dose of 200 mg every three weeks, along with a platinum-based chemotherapy doublet based on the result of ctDNA dynamics
Platinum DoubletDrug
Platinum-based chemotherapy (carboplatin AUC=5 + pemetrexed 500 mg/m² [adenocarcinoma] or nab-paclitaxel 260 mg/m² [squamous/other subtypes])
| Study group | Role | What they receive |
|---|---|---|
| Induction immunochemotherapy | Experimental | Not described Receives: Drug: PD-1 inhibitor; Drug: Platinum Doublet |
What is being measured
The primary outcome is the main question the study is designed to answer.
MPR
MPR is defined as ≤10% residual viable tumor in the resected specimen
Measured: From date of enrollment until one month after resection
Secondary outcomes (3)
R0 resection rate
defined as the percentage of patients that undergo R0 surgical resection after neoadjuvant treatment
Measured: From date of enrollment to an average of 18 weeks after the first dose
pCR rate
PCR rate is defined the percentage of patients with no residual viable tumor in the resected specimen
Measured: From date of enrollment until one month after resection
24-month EFS
24-month event-free survival rate in ITT population, defined as the interval between the start of neoadjuvant treatment and any progression of disease precluding surgical resection, progression of disease in the absence of surgery, progression or recurrence after surgery, or death from any cause, whichever occurred first
Measured: 36 months following initial treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2025
- Study start10 May 2025
- Primary completion10 May 2028 (estimated)
- Study completion10 May 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Non-small Cell Lung Cancer (NSCLC)Studies of the same condition, open and under way.
- More trials run by Sun Yat-sen UniversityThe sponsor's other registered studies.
- 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
- Sequential
- Masking
- None (open label)
- Enrolment
- 83 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Sun Yat-sen University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ze-Rui Zhao, Sun Yat-sen University
- Investigators
- Ting Zhou, Study chair, Sun Yat-Sen University Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06977074
- Sponsor's protocol ID
- B2025-176-01
- Acronym
- PROPHET
- Status last verified
- May 2025
- First submitted
- 1 May 2025
- Last updated
- 23 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Phase II Proof-of-Concept Trial on Circulating Tumor DNA (ctDNA)-Optimized Induction Immunochemotherapy Cycle Reduction for Resectable Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT06977074
- Acronym / sponsor ID
- PROPHET / B2025-176-01
- Conditions
- Non-small Cell Lung Cancer (NSCLC)
- Keywords
- Non-small cell lung cancer, ctDNA, Induction therapy, Immunochemotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 83 participants (estimated)
- Lead sponsor
- Sun Yat-sen UniversityUniversity, hospital or other
- Study start
- 10 May 2025 (actual)
- Primary completion
- 10 May 2028 (estimated)
- Study completion
- 10 May 2030 (estimated)
- First posted
- 16 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to evaluate the clinical value of ctDNA testing in guiding the optimization of immunochemotherapy cycles during induction treatment for resectable patients with NSCLC. The main questions it aims to answer are:
- Does ctDNA clearance indicate pathological complete response?
- Are additional cycles of immunochemotherapy necessary for patients who have ctDNA clearance after initial cycles of treatment? Researchers will use ctDNA dynamics to guide the cycles of induction treatment to see if some patients can avoid excessive cycles of treatment.
Detailed description
Advances in precision medicine have highlighted the potential of circulating tumor DNA (ctDNA) detection in NSCLC diagnosis, treatment efficacy monitoring, and prognosis evaluation. Induction immunotherapy combined with chemotherapy is now a standard treatment for patients with resectable NSCLC, but optimizing the number of immunochemotherapy cycles to enhance efficacy and reduce toxicity remains a critical clinical challenge. In this Phase II, proof-of-concept trial, around 83 patients with AJCC stage IIA-IIIB NSCLCs who are deemed resectable by an MDT team will participate to evaluate the potential role of dynamic ctDNA changes in guiding the cycle reduction of induction immunotherapy combined with chemotherapy while maintaining overall efficacy.
Eligible patients will receive 2 cycles (21-day intervals) of PD-1 inhibitor + platinum-based chemotherapy. Subsequent cycles (1-2 additional cycles) are determined by ctDNA status via tumour-agnostic strategies:
- For patients with ctDNA clearance: Randomized (1:1) to surgery or continued therapy.
- For patients with ctDNA persistence: Sequential 1-2 additional cycles. For all patients who are available to undergo surgery, the operation will be performed 4-6 weeks following the last cycle of treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Induction immunochemotherapy | Experimental | Drug: PD-1 inhibitor, Drug: Platinum Doublet |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Histologically/cytologically confirmed, untreated stage IIA-IIIB NSCLC (IASLC 8th edition).
- Deemed resectable by MDT.
- EGFR/ALK wild-type (non-squamous patients; squamous patients exempt).
- ECOG PS 0-1.
- Adequate organ function (neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, Hb >9 g/dL, Cr ≤1.5×ULN, AST/ALT ≤3×ULN).
Key exclusion criteria (6 listed)
- Active autoimmune diseases (exceptions: vitiligo, type I diabetes, stable hypothyroidism).
- Systemic corticosteroids (>10 mg prednisone equivalent/day) within 14 days.
- Grade 3-4 interstitial lung disease.
- Concurrent malignancies requiring treatment.
- Prior anti-PD-1/PD-L1/CTLA-4 therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PD-1 inhibitorTwo to four cycles of tislelizumab at a dose of 200 mg every three weeks, along with a platinum-based chemotherapy doublet based on the result of ctDNA dynamics | Drug | Induction immunochemotherapy |
| Platinum DoubletPlatinum-based chemotherapy (carboplatin AUC=5 + pemetrexed 500 mg/m² [adenocarcinoma] or nab-paclitaxel 260 mg/m² [squamous/other subtypes]) | Drug | Induction immunochemotherapy |
Primary outcome
MPR
Time frame: From date of enrollment until one month after resection
MPR is defined as ≤10% residual viable tumor in the resected specimen
3 secondary outcomes
R0 resection rate
Time frame: From date of enrollment to an average of 18 weeks after the first dose
pCR rate
Time frame: From date of enrollment until one month after resection
24-month EFS
Time frame: 36 months following initial treatment
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Ting Zhou study chair
Sun Yat-Sen University Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing PD-1 inhibitor and Platinum Doublet in people with Non-small Cell Lung Cancer (NSCLC), run by Sun Yat-sen University at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ze-Rui Zhao, MD PhD (+86 87343317, zhaozr@sysucc.org.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MPR (time frame: From date of enrollment until one month after resection). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.