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Advanced Malignant Solid TumorPhase 1/2NRT-01NCT03171220

Neoantigen Reactive T Cells Combined With SHR-1210 for Chinese Patients With Advanced Refractory Solid Tumors

A Phase 1/2 study testing Neoantigen Reactive T Cells(NRTs), SHR-1210 and Fludarabine in people with Advanced Malignant Solid Tumor, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School at 1 site in China.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) combined with programmed cell death-1(PD-1) inhibitor（SHR-1210）in the treatment of Chinese patients with advanced refractory solid tumors. Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Advanced Malignant Solid Tumor
What is being tested?
Neoantigen Reactive T Cells(NRTs), SHR-1210 and Fludarabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
40 participants
Where
1 siteChina
Study dates
1 Jun 2017to 31 Dec 2020
Phase
Phase 1/2
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 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult patients aged 18 to 75 years old
  • Histologic or cytologic confirmation of advanced refractory solid tumors with no available curative treatment options
  • At least one measurable disease: diameter ≥20mm or spiral computed tomography(CT)≥10mm; and can providing with tumor specimen (for testing the expression of PD -L1 and the infiltrating lymphocytes)
  • Must be human leukocyte antigen (HLA)-A2/A24/A11 positive
  • Eastern Cooperative Oncology Group(ECOG)<0-2 and expected survival time 3 months or more
  • At least one new antigen can induce T cell secrete interferon - gamma (IFN - gamma) twice as normal controls during the new antigens screening
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  • Without anticancer treatment more than one month
  • Hematology Index including: Neutrophile granulocyte greater than 1.5×10^9/L; Hemoglobin greater than 10g/dL; Platelet greater than 100×10^9/L
  • Biochemical index including: Serum bilirubin not greater than 1.5x upper limit of reference range (ULN); glutamic-pyruvic transaminase（ALT） or glutamic-oxalacetic transaminase（AST） not greater than 2.5x ULN; Creatinine clearance no less than 60ml/min
  • Peripheral venous channel open and no contraindications to separating lymphocytes
  • Negative pregnancy test for women of childbearing potential, and patients must be willing to practice birth control during the regimen
  • Provision of informed consent
  • Be able to follow the research program and follow up process

Who cannot join

  • Those who now are undergoing other antitumor drug therapy (including chemotherapy, systemic steroids therapy, surgery, target therapy or immune therapy);
  • Prior treatment with PD-1 monoclonal antibody(mAb） or PD-L1 mAb;
  • Prior malignancy active within the previous 5 years except for locally curable cancers that have been apparently cured, such as basal cell skin cancer or carcinoma in situ of the cervix;
  • History with pulmonary tuberculosis, and positive tests for Acquired Immune Deficiency Syndrome(HIV),hepatitis C virus(HCV),hepatitis B virus(HBV);
  • Patients with any active autoimmune disease or a documented history of autoimmune disease, or history of syndrome that required systemic steroids or immunosuppressive medications, such as hypophysitis, pneumonia, colitis, hepatitis, nephritis, hyperthyroidism or hypothyroidism; Severe, uncontrolled medical condition that would affect patients' compliance or obscure the interpretation of toxicity determination or adverse events, including active severe infection, uncontrolled diabetes, angiocardiopathy (heart failure > class II New York Heart Association(NYHA), heart block >II grade, myocardial infarction, unstable arrhythmia or unstable angina within past 6 months, cerebral infarction within past 3 months) or pulmonary disease ( interstitial pneumonia, obstructive pulmonary disease or symptomatic bronchospasm).
  • Evidence with central nervous system(CNS) disease
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  • Pregnant or nursing
  • Psychiatric medicines abuse without withdrawal, or history of psychiatric illness.
  • Hypersensitivity to investigational drugs or its components.

Trial locations and contacts

1 site in 1 country.

Baorui Liu, M.D & Ph.D contact

+86-25-83304616 ext. 61331

baoruiliu@nju.edu.cn

Zhengyun Zou, M.D & Ph.D contact

+86-25-83304616 ext. 61331

zouzhengyun@medmail.com.cn

China1 site, 1 recruiting

  • The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University and Clinical Cancer Institute of Nanjing University

    Nanjing, Jiangsu, 210008

    Baorui Liu, M.D. & Ph.D, +86-25-83304616 ext. 61331, baoruiliu@nju.edu.cn

    Zhengyun Zou, M.D. & Ph.D, +86-25-83304616 ext. 61331, zouzhengyun@medmail.com.cn

    Recruiting

Other trials in China

About this study

Official title: Single Center Single Arm Clinical Prospective Study of Neoantigen Reactive T Cells (NRTs) Combined With Programmed Cell Death-1（PD-1） Inhibitor in the Treatment of Chinese Patients With Advanced Refractory Solid Tumors

The purpose of this study is to see the safety and efficient of neoantigen reactive T cells (NRTs) combined with programmed cell death-1(PD-1) inhibitor（SHR-1210）in the treatment of Chinese patients with advanced refractory solid tumors.

Read the detailed description

The tumor-specific "none-self" immunogenic neoantigens encoded by either viral genes or somatic mutation genes, possess the potential to induce specific anti-cancer immunity, including cellular and humoral immune responses. Today, numerous clinical trials demonstrate that although these "none-self" antigens initiate the antigen-specific immunoglobulin G antibodies and cluster of differentiation 4（CD4）+/cluster of differentiation 8（CD8）+T-cells response, not all of them show a clinical benefit in the response rate, progression-free survival or overall survival.Immune tolerance induced by PD-1 or programmed cell death-ligand1（ PD-L1）maybe play a vital role for these negative outcomes.Personalized cell therapy plus checkpoint inhibitors maybe own a breakthrough in the treatment of those malignant diseases without standard options.Our center has successfully established a new method for preparing personalized neoantigen reactive T cells(NRTS) for adoptive cell therapy(ACT). Today, we will carry out a single center single arm clinical prospective study of NRTs combined with PD-1 inhibitor(SHR-1210) for the treatment of Chinese patients with advanced refractory solid tumors. Participants are assigned to receive 4 circles of cell therapy,and prior to each cycle's immunocytes treatment,preconditional chemotherapy and SHR-1210 will be carried out, and IL-2 continuous intravenous infusion（CIV） will also be given for 5 consecutive days after each time's cell infusion. The safety and clinical response rate（RR） are evaluated. Biomarkers and immunological markers are also monitored.

Being tested
Neoantigen Reactive T Cells(NRTs), SHR-1210, Fludarabine, Cyclophosphamide, Interleukin-2
Keywords
Neoantigen, Neoantigen Reactive T cells (NRTs), PD-1 Inhibitor, Advanced Solid Tumor, Adoptive Cell Therapy(ACT), PD-1 antibody, SHR1210

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Neoantigen Reactive T Cells(NRTs)Biological

    Neoantigen Reactive T Cells in an expected volume of 100 milliliter（mL） will be given by intravenous injection over 2-10 minutes through either a peripheral or a central line.

  • SHR-1210Biological

    SHR-1210 200mg will be administered as an intravenous infusion over 60 minutes.

  • FludarabineDrug

    Also called FLU

    Fludarabine(FLU) 30mg/m2/d×3d，3 days prior to each NRTs infusion as preconditional chemotherapy.

  • CyclophosphamideDrug

    Also called CTX

    Cyclophosphamide(CTX) 300mg/m2/d×3d，3 days prior to each NRTs infusion as preconditional chemotherapy.

  • Interleukin-2Biological

    Also called IL-2

    Interleukin-2(IL-2)will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit per day.

Study groups in NCT03171220
Study groupRoleWhat they receive
Neoantigen Reactive T Cells + SHR-1210ExperimentalPeripheral blood lymphocytes will be collected and neoantigen reactive T cells(NRTs) will be generated in the laboratory;Both Fludarabine 30mg/m2/D and Cyclophosphamide 300mg/m2/D will be i.v. for 3 days before cell infusion; NRTs 0.5~1 x 10^10, will be i.v.Q3 weeks for total 4 doses;programmed cell death-1（PD1） inhibitor SHR-1210,200mg,will be i.v. Q3 weeks for total 4 doses,2 day2 prior to each NRTs infusion;Interleukin-2 (IL-2) will be continuous intravenous infused since the first day of the cell infusion for 5 consecutive days, 4000,000 international unit per day.All Patients will receive a total of 4 cycles of treatment.
Receives: Biological: Neoantigen Reactive T Cells(NRTs); Biological: SHR-1210; Drug: Fludarabine; Drug: Cyclophosphamide; Biological: Interleukin-2

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of participants with Adverse Events

    using Common Terminology Criteria for Adverse Events (CTCAE v4.0) in patients

    Measured: up to 6 months

Secondary outcomes (2)

  1. Response Rate

    Response Rate（RR） will be evaluated according Response Evaluation Criteria in Solid Tumors

    Measured: At 3, 6 and 12 months

  2. Progression free survival (PFS)

    the duration of progression free survival is measured from the time of treatment to the first date that recurrent or progressive disease or for any reason of death is objectively documented.

    Measured: At 6,9 and 12 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted31 May 2017
  2. Study start1 Jun 2017
  3. Primary completion31 Dec 2019 (estimated)
  4. Study completion31 Dec 2020 (estimated)

Resources

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03171220
Sponsor's protocol ID
NDTHNanjing
Acronym
NRT-01
Status last verified
Jun 2017
First submitted
13 May 2017
Last updated
6 Jun 2017
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided

Publications

  • Gros A, Parkhurst MR, Tran E, Pasetto A, Robbins PF, Ilyas S, Prickett TD, Gartner JJ, Crystal JS, Roberts IM, Trebska-McGowan K, Wunderlich JR, Yang JC, Rosenberg SA. Prospective identification of neoantigen-specific lymphocytes in the peripheral blood of melanoma patients. Nat Med. 2016 Apr;22(4):433-8. doi: 10.1038/nm.4051. Epub 2016 Feb 22.

    PubMed 26901407

  • Desrichard A, Snyder A, Chan TA. Cancer Neoantigens and Applications for Immunotherapy. Clin Cancer Res. 2016 Feb 15;22(4):807-12. doi: 10.1158/1078-0432.CCR-14-3175. Epub 2015 Oct 29.

    PubMed 26515495

  • Rosenberg SA, Restifo NP. Adoptive cell transfer as personalized immunotherapy for human cancer. Science. 2015 Apr 3;348(6230):62-8. doi: 10.1126/science.aaa4967.

    PubMed 25838374

  • Su S, Zou Z, Chen F, Ding N, Du J, Shao J, Li L, Fu Y, Hu B, Yang Y, Sha H, Meng F, Wei J, Huang X, Liu B. CRISPR-Cas9-mediated disruption of PD-1 on human T cells for adoptive cellular therapies of EBV positive gastric cancer. Oncoimmunology. 2016 Nov 22;6(1):e1249558. doi: 10.1080/2162402X.2016.1249558. eCollection 2017.

    PubMed 28197365

  • Stevanovic S, Pasetto A, Helman SR, Gartner JJ, Prickett TD, Howie B, Robins HS, Robbins PF, Klebanoff CA, Rosenberg SA, Hinrichs CS. Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer. Science. 2017 Apr 14;356(6334):200-205. doi: 10.1126/science.aak9510.

    PubMed 28408606

  • Tran E, Robbins PF, Lu YC, Prickett TD, Gartner JJ, Jia L, Pasetto A, Zheng Z, Ray S, Groh EM, Kriley IR, Rosenberg SA. T-Cell Transfer Therapy Targeting Mutant KRAS in Cancer. N Engl J Med. 2016 Dec 8;375(23):2255-2262. doi: 10.1056/NEJMoa1609279.

    PubMed 27959684

  • Parkhurst M, Gros A, Pasetto A, Prickett T, Crystal JS, Robbins P, Rosenberg SA. Isolation of T-Cell Receptors Specifically Reactive with Mutated Tumor-Associated Antigens from Tumor-Infiltrating Lymphocytes Based on CD137 Expression. Clin Cancer Res. 2017 May 15;23(10):2491-2505. doi: 10.1158/1078-0432.CCR-16-2680. Epub 2016 Nov 8.

    PubMed 27827318

  • Chen F, Zou Z, Du J, Su S, Shao J, Meng F, Yang J, Xu Q, Ding N, Yang Y, Liu Q, Wang Q, Sun Z, Zhou S, Du S, Wei J, Liu B. Neoantigen identification strategies enable personalized immunotherapy in refractory solid tumors. J Clin Invest. 2019 Mar 5;129(5):2056-2070. doi: 10.1172/JCI99538. Print 2019 May 1.

    PubMed 30835255

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Neoantigen Reactive T Cells(NRTs), SHR-1210 and Fludarabine in people with Advanced Malignant Solid Tumor, run by The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School 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 13 inclusion and 9 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: status not confirmed, as of the sponsor's last update on 6 Jun 2017. 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 combined 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.

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?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Baorui Liu, M.D & Ph.D (+86-25-83304616 ext. 61331, baoruiliu@nju.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants with Adverse Events (time frame: up to 6 months). 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 NCT03171220, which also lists 8 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 6 Jun 2017.

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