High-Risk Resectable NSCLCPhase 1NCT03732664
ICIs Neoadjuvant Therapy in Resectable Non-Small-Cell Lung Cancer
A Phase 1 study testing Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab in people with High-Risk Resectable NSCLC, run by Second Affiliated Hospital, Zhejiang University, School of Medicine at 1 site in China.
Trial summary
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- High-Risk Resectable NSCLC
- What is being tested?
- Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteChina
- Study dates
- 1 Oct 2018to 23 Mar 2023
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 proven non-small-cell lung cancer (core biopsy required).
- Squamous or non-squamous histology.
- Diagnostic core biopsy specimens must be reviewed by a faculty pathologist at The Second Affiliated Hospital Zhejiang University School of Medicine.
- Either a formalin fixed paraffin block or a minimum of fifteen 5-micron tissue sections (slides) of tumor biopsy sample must be available for biomarker evaluation (study pathologist must review for adequacy of sampling). This can be obtained from archived tissues, or from a new biopsy if needed.
- Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at The Second Affiliated Hospital Zhejiang University School of Medicine. This may include clinical stage IA3 (≥2cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.
- ECOG performance status 0-1.
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- Adequate organ function as follows:
- Leukocytes ≥ 2,000/mm3.
- Absolute neutrophil count (ANC) ≥ 1000/mm3.
- Platelet count ≥ 100,000/mm3.
- Hemoglobin ≥ 9 g/dL.
- Creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥40 mL/min (if using the Cockcroft-Gault formula below):
- Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL.
- Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL.
- Total Bilirubin ≤ 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin < 3.0 mg/dL).
- AST(SGOT), ALT(SGPT), and alkaline phosphatase ≤ 3 times the upper limit of normal.
- Subjects must have adequate lung function to permit surgical resection determined by pre-enrollment pulmonary function tests to include DLCO.
- The effects of nivolumab on the developing human fetus are unknown. For this reason, women of child-bearing potential (WOCBP) and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for up to 23 weeks after the last dose of nivolumab. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Sexually active fertile men must use effective barrier birth control if their partners are WOCBP for up to 31 weeks after the last dose of nivolumab. WOCBP must have a negative serum or urine pregnancy test (minimum sensitivity 25 IU/L or equivalent units of HCG) within two weeks of registration. Women must not be breastfeeding.
- Patient understands the study regimen, its requirements, risks and discomforts and is able and willing to sign the informed consent form. Voluntary signed and dated IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines must be obtained before the performance of any protocol related procedures that are not part of normal patient care. Subjects must be competent to report AEs, understand the drug dosing schedule and use of medications to control AEs.
Who cannot join
- Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- Administration of chemotherapy or any other cancer therapy in the pre-operative period.
- Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
- Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
- Subjects with a history of symptomatic interstitial lung disease.
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- Active systemic infection requiring therapy, positive tests for Hepatitis B surface antigen or Hepatitis C ribonucleic acid (RNA).
- Known positive history or positive test for Human Immunodeficiency Virus or
- Acquired ImmunoDeficiency Syndrome (AIDS).
- History of allergy to study drug components.
- Women who are pregnant or nursing.
- Men with female partners (WOCBP) that are not willing to use contraception.
- Prior therapy with an anti-PD-1, anti-PD-L1, anti-PDL-2, or anti-CTLA-4 antibody (or any other antibody targeting T cell co-regulatory pathways).
- Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events.
- Prisoners or subjects who are involuntarily incarcerated or compulsorily detained for treatment of either a psychiatric or physical (e.g. infectious disease) illness.
Trial locations and contacts
1 site in 1 country.
China1 site
The Second Affiliated Hospital Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310009
About this study
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting.
Read the detailed description
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 or anti-PD-L1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.
- Conditions
- High-Risk Resectable NSCLC
- Being tested
- Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, DurvalumabDrug
Also called BMS-936558, MDX1106, Keytruda
One to four doses of anti-PD-1 or anti-PD-L1 antibody will be administered to enrolled patients on Day -56, Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.
| Study group | Role | What they receive |
|---|---|---|
| Single arm | Other | Not described Receives: Drug: Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Adverse effects
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites. Safety will also be measured by recording Grade 3 and 4 CTCAE 4.03 listed adverse events that occur while a subject is participating in the study.
Measured: 8 weeks
Secondary outcomes (3)
Rate of Enrollment
Feasibility will be measured by the rate of enrollment of the 40 subjects at the 2 sites.
Measured: 8 weeks
Pathologic Response
To assess pathologic response to neoadjuvant nivolumab in resected tumor and lymph nodes. The rate of major pathologic response, defined as <10% residual viable tumor cells in the resection specimen will be compared to historic data with neoadjuvant chemotherapy.
Measured: 6 weeks
Radiographic Response
To assess radiographic response to neoadjuvant nivolumab using RECIST 1.1.
Measured: 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Nov 2018
- Study start1 Oct 2018
- Primary completion23 Mar 2023
- Study completion23 Mar 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for High-Risk Resectable NSCLCStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital, Zhejiang University, School of MedicineThe 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Anti-PD-1 or anti-PD-L1 antibody administration: One to four doses of anti-PD-1 or anti-PD-L1 antibody will be administered to enrolled patients on Day -56, Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03732664
- Status last verified
- Oct 2021
- First submitted
- 29 Oct 2018
- Last updated
- 24 Mar 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.
PubMed 29658848Chen Y, Shao Z, Hao Z, Xin Z, Chen X, Huang L, Chen D, Lin M, Liu Q, Xu X, Li J, Wu D, Yan J, Chai Y, Wu P. Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC. J Immunother Cancer. 2024 Aug 12;12(8):e007854. doi: 10.1136/jitc-2023-007854.
PubMed 39134346
Study at a glance
From the registry record, last updated by the sponsor on 24 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- ICIs Neoadjuvant Therapy in Resectable Non-Small-Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT03732664
- Conditions
- High-Risk Resectable NSCLC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- Second Affiliated Hospital, Zhejiang University, School of MedicineUniversity, hospital or other
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 23 Mar 2023 (actual)
- Study completion
- 23 Mar 2023 (actual)
- First posted
- 6 Nov 2018 (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 proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting.
Detailed description
The proposed study will evaluate the safety and feasibility of preoperative administration nivolumab in patients with high-risk resectable NSCLC, and will facilitate a comprehensive exploratory characterization of the tumor immune milieu and circulating immune cells and soluble factors in these patients. Data obtained in this study will provide valuable information for planning further prospective clinical trials of anti-PD-1 or anti-PD-L1 in NSCLC, both in the peri-operative and advanced disease setting. Ultimately, it is highly desirable to discover prospective biomarkers of response and toxicity to allow patients with NSCLC who are most likely to derive benefit to receive anti-PD-1 or anti-PD-L1 treatment, and conversely to minimize the risk of toxicity and ineffective treatment for patients who are unlikely to benefit.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Anti-PD-1 or anti-PD-L1 antibody administration: One to four doses of anti-PD-1 or anti-PD-L1 antibody will be administered to enrolled patients on Day -56, Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days.
| Arm | Type | Receives |
|---|---|---|
| Single arm | Other | Drug: Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Histologically proven non-small-cell lung cancer (core biopsy required).
- Stage - High risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at The Second Affiliated Hospital Zhejiang University School of Medicine. This may include clinical stage IA3 (≥2cm), II and IIIA(see Appendix A). Subjects with N3 nodal involvement are not included.
- ECOG performance status 0-1.
- Adequate organ function as follows:
- Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL.
Key exclusion criteria (15 listed)
- Subjects are excluded if they have an active, known or suspected autoimmune disease. Subjects are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger.
- Subjects are excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. As there is potential for hepatic toxicity with nivolumab or nivolumab/ipilimumab combinations, drugs with a predisposition to hepatoxicity should be used with caution in patients treated with nivolumab-containing regimen.
- Administration of chemotherapy or any other cancer therapy in the pre-operative period.
- Subjects with active concurrent malignancies are excluded i.e. cancers other than NSCLC (except non melanoma skin cancers, in situ bladder, gastric, breast, colon or cervical cancers/dysplasia).
- Subjects with brain metastasis are excluded from this study, and all patients should have brain imaging (either MRI brain or CT brain with contrast) prior to enrollment.
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 |
|---|---|---|
| Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, DurvalumabAlso: BMS-936558, MDX1106, KeytrudaOne to four doses of anti-PD-1 or anti-PD-L1 antibody will be administered to enrolled patients on Day -56, Day -42, Day -28, and Day-14 (+/- two days) prior to planned surgery on Day 0 or up to +10 days. | Drug | Single arm |
Primary outcome
Safety and Adverse effects
Time frame: 8 weeks
Safety will be measured by drawing safety labs. (CBC and a Chemistry Panel will be drawn at 2 week intervals during Nivolumab administration). Grade 3 and 4 lab abnormalities will be recorded from both participating sites. Safety will also be measured by recording Grade 3 and 4 CTCAE 4.03 listed adverse events that occur while a subject is participating in the study.
3 secondary outcomes
Rate of Enrollment
Time frame: 8 weeks
Pathologic Response
Time frame: 6 weeks
Radiographic Response
Time frame: 5 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Mar 2023.
- Background: PubMed 29658848Forde PM, Chaft JE, Smith KN, Anagnostou V, Cottrell TR, Hellmann MD, Zahurak M, Yang SC, Jones DR, Broderick S, Battafarano RJ, Velez MJ, Rekhtman N, Olah Z, Naidoo J, Marrone KA, Verde F, Guo H, Zhang J, Caushi JX, Chan HY, Sidhom JW, Scharpf RB, White J, Gabrielson E, Wang H, Rosner GL, Rusch V, Wolchok JD, Merghoub T, Taube JM, Velculescu VE, Topalian SL, Brahmer JR, Pardoll DM. Neoadjuvant PD-1 Blockade in Resectable Lung Cancer. N Engl J Med. 2018 May 24;378(21):1976-1986. doi: 10.1056/NEJMoa1716078. Epub 2018 Apr 16.
- Derived from this study: PubMed 39134346Chen Y, Shao Z, Hao Z, Xin Z, Chen X, Huang L, Chen D, Lin M, Liu Q, Xu X, Li J, Wu D, Yan J, Chai Y, Wu P. Epithelium/imcDC2 axis facilitates the resistance of neoadjuvant anti-PD-1 in human NSCLC. J Immunother Cancer. 2024 Aug 12;12(8):e007854. doi: 10.1136/jitc-2023-007854.
- 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. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nivolumab, Pembrolizumab, Toripalimab, Sintilimab, Sintilimab, Tislelizumab, Durvalumab in people with High-Risk Resectable NSCLC, run by Second Affiliated Hospital, Zhejiang University, School of Medicine 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 19 inclusion and 15 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: finished, as of the sponsor's last update on 24 Mar 2023. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety and Adverse effects (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03732664, which also lists 2 linked publications.
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 24 Mar 2023.