NAD+ Supplement（NMN）With Radioimmunotherapy in Advanced NSCLC

NCT06966583 | Not Yet Recruiting Phase 1

• 2 other identifiers: HX257253257253
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a phase I, single center (West China Hospital, Sichuan University) study aimed at investigating the safety and efficacy of NMN supplements combined with chemotherapy and radiation therapy for second-line and above treatment of advanced NSCLC.

Conditions

Solid Tumor; Non Small Cell Lung Cancer

Keywords

Radiotherapy; Stereotactic Ablative Radiotherapy; Immunotherapy; NMN

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events and/or Dose Limiting Toxicities of NMN supplements in RT+ICI treatment

  Adverse Events and/or Dose Limiting Toxicity graded per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0

  from enrollment through 30 days after last dosing, up to 24 months

Secondary Outcomes (3)

• Progression Free Survival (PFS)

  up to 24 months after the enrollment

• Objective Response Rate (ORR)

  up to 24 months after the enrollment

• Overall Survival (OS)

  up to 24 months after the enrollment

Other Outcomes (1)

• Exploratory indicators

  up to 24 months after the enrollment

Study Arms (1)

NAD supplement NMN+PD-1 inhibitor+radiotherapy

EXPERIMENTAL

This is a dose escalation study that involves administering radiation therapy (RT) doses, PD-1 inhibitors, and NAD supplements

Dietary Supplement: NAD supplement; Radiation: Radiotherapy; Drug: Immunotherapy

Interventions

NAD supplement DIETARY_SUPPLEMENT

NAD supplement NMN：NMN12000 GeneHarbor

Also known as: NMN

NAD supplement NMN+PD-1 inhibitor+radiotherapy

Radiotherapy RADIATION

Low Dose Radiotherapy or Stereotactic Ablative Radiotherapy or Conventional Radiotherapy

NAD supplement NMN+PD-1 inhibitor+radiotherapy

Immunotherapy DRUG

PD-1 inhibitor

Also known as: PD-1 inhibitor

NAD supplement NMN+PD-1 inhibitor+radiotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• According to the 8th edition TNM staging of lung cancer by the International Association for the Study of Lung Cancer and the Joint Committee on Cancer Classification in the United States, metastatic (stage IV) non-small cell lung cancer with histological or cytological evidence that cannot be treated surgically and cannot receive curative concurrent chemoradiotherapy, and has received at least first-line treatment.
• At least 2 measurable target lesions (RECIST v1.1 standard), intracranial lesions are not included as radiation therapy lesions or observation lesions due to immune exemption, liver lesions are not included as observation lesions due to immune exemption, and bone lesions are not included as observation lesions due to non measurability. For a lesion that has previously received radiotherapy, only when there is clear disease progression after radiotherapy can it be considered a target lesion. The patient plans to undergo radiotherapy combined with PD-1 inhibitors, or is currently receiving PD-1 inhibitor treatment and has undergone or plans to undergo radiotherapy within one month from the date of enrollment.
• Agree to provide tumor tissue specimens, which can be previously archived or freshly obtained, for the detection of biomarkers.
• Voluntarily sign a written informed consent form. The informed consent form must be signed before any protocol related procedures (which are not part of the subject's routine medical care) are carried out. The subject signs the informed consent form and signs the date. Participants must be willing and able to comply with the scheduled visits, treatment plans, laboratory tests, and other requirements of the study. At the time of signing the informed consent form, both males and females are eligible for age between 18 and 75 years old.
• The physical fitness score of the Eastern Cooperative Oncology Group (ECOG) in the United States is 0 or 1, with an expected survival period of ≥ 3 months.
• Can provide confirmation of EGFR through tissue based testing, ALK and ROS1 are both reported as wild-type. For non squamous NSCLC patients who have not been confirmed to have wild-type EGFR and wild-type ALK, tumor samples (archived or fresh, primary or metastatic) need to be collected before enrollment for evaluation of EGFR and ALK testing (in local or central laboratories). If there is no archived tumor tissue, fresh tumor biopsy samples must be collected at baseline.
• The laboratory test results during the screening period indicate that the subjects have good organ function (no blood components or cell growth factors are allowed to support treatment within the first 2 weeks of randomization): Hematology: i. Absolute neutrophil NEC ≥ 1.5 × 10 \^ 9/L; Ii. Platelet count ≥ 100 × 10 \^ 9/L; Iii. Hemoglobin ≥ 9.0g/dL. B Kidney: i. If the calculated creatinine clearance rate (CrCl) is ≥ 50 mL/min, the Cockcroft Gault formula will be used to calculate CrCl (Cockcroft DW, 1976) CrCL (mL/min)={(140 age) × body weight (kg) × F}/(SCr (mg/dL) × 72), where F=1 for females and F=0.85 for males; SCr=serum creatinine. Liver: i. Serum total bilirubin (TBil) ≤ 1.5 × ULN; For subjects with liver metastasis or confirmed/suspected Gilbert disease, TBil ≤ 3 × ULN ii AST and ALT ≤ 2.5 × ULN; For subjects with liver metastasis, AST and ALT ≤ 5 × ULN d coagulation function: i. International standardized ratio and activated partial thromboplastin time ≤ 1.5 × ULN (unless the subject is receiving anticoagulant therapy and coagulation parameters (PT, INR, and APTT) are within the expected range of anticoagulant therapy at screening).

You may not qualify if:

• Pregnant or lactating women.
• Researchers believe that any condition that may pose a risk to receiving study treatment or interfere with the evaluation of study treatment, subject safety, or interpretation of study results.
• Previously received treatment with EGFR antagonists or ALK antagonists.
• Previously participated in experimental drug studies or received research treatment or used experimental devices within 4 weeks prior to the first administration.
• Simultaneously enrolled in another clinical study, unless it is an observational, non interventional clinical study or an interventional study with a follow-up period (defined as the time from the first administration to the last administration of the previous clinical study being more than 4 weeks or the study drug having more than 5 half lives).
• Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation.
• Suffering from active, known or suspected autoimmune diseases, or having a history of autoimmune diseases, except for vitiligo, hair loss, Graves' disease, psoriasis or eczema that do not require systemic treatment within the past 2 years, hypothyroidism (caused by autoimmune thyroiditis) that only requires stable doses of hormone replacement therapy, and type I that only requires stable doses of insulin replacement therapy, diabetes or childhood asthma that have completely alleviated without any intervention after adulthood, or whose disease will not recur without external triggers.
• Active or previously recorded inflammatory bowel disease (such as Crohn's disease, ulcerative colitis, or chronic diarrhea).
• Subjects who require systemic treatment with corticosteroids (\>10 mg/day prednisone equivalent dose) or other immunosuppressive drugs within 14 days prior to the first administration. Except for the following: a) If there is no active autoimmune disease, inhaled, ophthalmic, or topical corticosteroids and corticosteroids at doses not exceeding 10mg/day effective dose of prednisone are allowed for treatment. b) The dosage of systemic corticosteroids at physiological doses does not exceed 10 mg/day of prednisone or equivalent doses of other corticosteroids. c) Corticosteroids are used as preventive medication for hypersensitivity reactions (such as medication before CT examination).
• Known history of primary immunodeficiency virus infection.
• Suffering from other active malignant tumors within the first 5 years of enrollment. Locally curable cancers (manifested as cured) are excluded, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or breast carcinoma in situ.
• Having undergone major surgical procedures (defined by the investigator, such as open biopsy, severe trauma, etc.) within 28 days prior to the first administration. Note: For the replacement of intravenous drip tubes, it is acceptable. Within 30 days after the first administration (as determined by the researcher), there are significant surgical plans or complete recovery from previous surgeries. Local surgeries (such as placement of systemic ports, hollow core needle biopsy, and prostate biopsy) are allowed, provided that the surgery is completed at least 24 hours before the first administration of the investigational therapeutic drug.
• Subjects who have not recovered from the toxicity and/or complications of previous interventions to NCI-CTC AE ≤ 1 degree (excluding hair loss and fatigue) prior to their first medication.
• History of gastrointestinal perforation and/or fistula within 6 months prior to initial administration.
• Known history of interstitial lung disease. Exclude subjects highly suspected of having interstitial pneumonia; Or subjects who may interfere with the detection or treatment of suspected drug-related pulmonary toxicity; Or other moderate to severe lung diseases that seriously affect lung function.

Sponsors & Collaborators

• Sichuan University: lead

Study Sites (1)

West China Hospital, Sichuan University

Chengdu, Sichuan, 610041, China

Location

Related Publications (10)

• Wang Y, Wang F, Wang L, Qiu S, Yao Y, Yan C, Xiong X, Chen X, Ji Q, Cao J, Gao G, Li D, Zhang L, Guo Z, Wang R, Wang H, Fan G. NAD+ supplement potentiates tumor-killing function by rescuing defective TUB-mediated NAMPT transcription in tumor-infiltrated T cells. Cell Rep. 2021 Aug 10;36(6):109516. doi: 10.1016/j.celrep.2021.109516.

  PMID: 34380043 BACKGROUND

• Song Q, Zhou X, Xu K, Liu S, Zhu X, Yang J. The Safety and Antiaging Effects of Nicotinamide Mononucleotide in Human Clinical Trials: an Update. Adv Nutr. 2023 Nov;14(6):1416-1435. doi: 10.1016/j.advnut.2023.08.008. Epub 2023 Aug 22.

  PMID: 37619764 BACKGROUND

• Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, Friedewald W. Fifteen year mortality in Coronary Drug Project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986 Dec;8(6):1245-55. doi: 10.1016/s0735-1097(86)80293-5.

  PMID: 3782631 BACKGROUND

• Lv H, Lv G, Chen C, Zong Q, Jiang G, Ye D, Cui X, He Y, Xiang W, Han Q, Tang L, Yang W, Wang H. NAD+ Metabolism Maintains Inducible PD-L1 Expression to Drive Tumor Immune Evasion. Cell Metab. 2021 Jan 5;33(1):110-127.e5. doi: 10.1016/j.cmet.2020.10.021. Epub 2020 Nov 9.

  PMID: 33171124 BACKGROUND

• Wu S, Zhang R. CD38-expressing macrophages drive age-related NAD+ decline. Nat Metab. 2020 Nov;2(11):1186-1187. doi: 10.1038/s42255-020-00292-5. No abstract available.

  PMID: 33199923 BACKGROUND

• Zhang X, Niedermann G. Abscopal Effects With Hypofractionated Schedules Extending Into the Effector Phase of the Tumor-Specific T-Cell Response. Int J Radiat Oncol Biol Phys. 2018 May 1;101(1):63-73. doi: 10.1016/j.ijrobp.2018.01.094. Epub 2018 Feb 3.

  PMID: 29534901 BACKGROUND

• Yin L, Xue J, Li R, Zhou L, Deng L, Chen L, Zhang Y, Li Y, Zhang X, Xiu W, Tong R, Gong Y, Huang M, Xu Y, Zhu J, Yu M, Li M, Lan J, Wang J, Mo X, Wei Y, Niedermann G, Lu Y. Effect of Low-Dose Radiation Therapy on Abscopal Responses to Hypofractionated Radiation Therapy and Anti-PD1 in Mice and Patients With Non-Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2020 Sep 1;108(1):212-224. doi: 10.1016/j.ijrobp.2020.05.002. Epub 2020 May 15.

  PMID: 32417411 BACKGROUND

• Park SS, Dong H, Liu X, Harrington SM, Krco CJ, Grams MP, Mansfield AS, Furutani KM, Olivier KR, Kwon ED. PD-1 Restrains Radiotherapy-Induced Abscopal Effect. Cancer Immunol Res. 2015 Jun;3(6):610-9. doi: 10.1158/2326-6066.CIR-14-0138. Epub 2015 Feb 19.

  PMID: 25701325 BACKGROUND

• Deng L, Liang H, Burnette B, Beckett M, Darga T, Weichselbaum RR, Fu YX. Irradiation and anti-PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014 Feb;124(2):687-95. doi: 10.1172/JCI67313. Epub 2014 Jan 2.

  PMID: 24382348 BACKGROUND

• Kaur P, Asea A. Radiation-induced effects and the immune system in cancer. Front Oncol. 2012 Dec 17;2:191. doi: 10.3389/fonc.2012.00191. eCollection 2012.

  PMID: 23251903 BACKGROUND

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Radiotherapy; Immunotherapy; Immune Checkpoint Inhibitors

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Therapeutics; Immunomodulation; Biological Therapy; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Antineoplastic Agents, Immunological; Antineoplastic Agents; Therapeutic Uses

Study Officials

• Jianxin Xue, doctoral

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xuanwei Zhang, doctoral

CONTACT

18829573328; 18609274107@163.com

You Lu, doctoral

CONTACT

18829573328; radyoulu@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Division of Thoracic Tumor Multimodality Treatment

Study Record Dates

• First Submitted: April 2, 2025
• First Posted: May 12, 2025
• Study Start: May 1, 2025
• Primary Completion (Estimated): June 30, 2027
• Study Completion (Estimated): November 30, 2027
• Last Updated: May 12, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)