Phase I Clinical Study of α-PD-L1/DLL3 CAR-T in Patients With R/R SCLC

NCT06348797 | Recruiting Phase 1

• 1 other identifier: BHP01-01
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

A study to evaluate the safety and feasibility of α-PD-L1/4-1BB DLL3 Chimeric Antigen Receptor (CAR)-T (BHP01) in patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC) and determine the appropriate CAR-T cell dose. Next, In dose expansion phase, patients were assign two groups with/without bridge radiotherapy.

Conditions

Small Cell Lung Cancer Extensive Stage

Keywords

Extensive Stage-SCLC; DLL3 CAR-T; Bridge Radiotherapy

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT)

  Safety

  day1-day28

Secondary Outcomes (6)

• Objective Response Rate (ORR)

  up to 1 year after the enrollment

• Progression-free survival (PFS)

  up to 1 year after the enrollment

• Disease control rate (DCR)

  up to 1 year after the enrollment

• Duration of response (DOR)

  up to 1 year after the enrollment

• Overall-Survival (OS)

  up to 1 year after the enrollment

Study Arms (1)

α-PD-L1/4-1BB DLL3 CAR-T (BHP01) Treatment

EXPERIMENTAL

The Patients enrolled will be sequentially assigned to the corresponding dose level, BHP01 was administered intravenous infusion at different cell dose levels. The patients were received multiple-dose infusion according to investigator's evaluation.

Drug: α-PD-L1/4-1BB DLL3 CAR-T (BHP01)

Interventions

α-PD-L1/4-1BB DLL3 CAR-T (BHP01) DRUG

Preconditioning with fludarabine, cyclophosphamide, based chemotherapy regimen at sub-clinical doses; Bridge radiotherapy with 15 Gray (Gy)/5 fractions; α-PD-L1/4-1BB DLL3 CAR-T (BHP01): the first dose was 5x10\^5/kg.

Also known as: Bridge radiotherapy

α-PD-L1/4-1BB DLL3 CAR-T (BHP01) Treatment

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with recurrent or refractory small cell lung cancer (SCLC) confirmed by histology or cytology who have relapsed or progressed after treatment with one previous platinum-based regimen;
• Patients can provide sufficient tumor tissue (fresh or paraffin sections, etc.);
• Age 18 \~70 (including boundary), for both men and women;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1;
• Life expectancy ≥3 months;
• At least one extracranial measurable lesion (RECIST v1.1) exists；for lesion after radiotherapy， must be confirmed that the lesion has progressed ;
• Patients in limited-stage at the initial diagnosis must undergo radical thoracic radiotherapy and the time of tumor progression is not less than 3 months from the end of radiotherapy, or radical thoracic dose radiotherapy cannot be performed for specific reasons;
• The test results of human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg), hepatitis C and syphilis were negative at screening;
• Female patients or male reproductive age patients and their partners should agree to effective contraception from sighing Informed Consent Form (ICF) to 6 months after the last BHP01 infusion.

You may not qualify if:

• Patients with known primary Central Nervous System (CNS) tumor, or meningeal metastasis, or patients with unstable CNS metastasis (symptomatic, requiring hormonal therapy within 4 weeks before investigational treatment, or no radiographic evidence of stabilization of the lesion for more than 4 weeks);
• Received major surgical procedures （except for diagnosis） within 4 weeks before PBMCs collection, or are expected to require major surgical procedures during the study;
• Received Chinese herbal medicine or Chinese patent medicine for anti-tumor indications within 7 days before Peripheral Blood Mononuclear Cells (PBMCs) collection;
• Patients with a history of idiopathic pulmonary fibrosis, mechanical pneumonia (such as bronchiolitis obliterans), drug-induced pneumonia or idiopathic pneumonia, or evidence of active pneumonia by chest computer tomography (CT) at screening \[a history of radiation pneumonia (fibrosis) in the irradiated field may participate in this study\];
• Poorly controlled pleural effusion, pericardial effusion, or ascites requiring repeated drainage procedures (once a month or more frequently);
• Poorly controlled or symptomatic hypercalcemia (ionic calcium\> 1.5 mmol/L, calcium\> 12 mg/dL or corrected calcium\> ULN);
• Presence of active or previous autoimmune diseases or immunodeficiencies, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, etc.;
• Severe infection within 4 weeks before the start of PBMCs collection, including but not limited to hospitalization due to infection, bacteremia, severe pneumonia, or any active infection that may affect the patient's safety;
• Serious cardiovascular and cerebrovascular diseases (such as heart disease ≥New York Heart Association class II, myocardial infarction or cerebrovascular accident), unstable arrhythmia or unstable angina pectoris within 3 months before PBMCs collection;
• Previous treatment with DLL 3 target drugs or CAR-T or other gene-modified T cells;
• Received any other Investigational drug within 28 days prior to PBMCs collection;
• A history of mental illness;
• Incapacitated persons or persons with limited capacity;
• pregnant or lactating females; Males or females who are unwilling to use adequate contraception; Females of childbearing potential are required to undergo a pregnancy study during the screening period;

Sponsors & Collaborators

• Sichuan University: lead
• Chengdu Brilliant Pharmaceutical Co., Ltd.: collaborator

Study Sites (1)

West China Hospital Sichuan University

Chengdu, Sichuan, 610041, China

RECRUITING

Related Publications (8)

• Ahn MJ, Cho BC, Felip E, Korantzis I, Ohashi K, Majem M, Juan-Vidal O, Handzhiev S, Izumi H, Lee JS, Dziadziuszko R, Wolf J, Blackhall F, Reck M, Bustamante Alvarez J, Hummel HD, Dingemans AC, Sands J, Akamatsu H, Owonikoko TK, Ramalingam SS, Borghaei H, Johnson ML, Huang S, Mukherjee S, Minocha M, Jiang T, Martinez P, Anderson ES, Paz-Ares L; DeLLphi-301 Investigators. Tarlatamab for Patients with Previously Treated Small-Cell Lung Cancer. N Engl J Med. 2023 Nov 30;389(22):2063-2075. doi: 10.1056/NEJMoa2307980. Epub 2023 Oct 20.

  PMID: 37861218 BACKGROUND

• Paz-Ares L, Champiat S, Lai WV, Izumi H, Govindan R, Boyer M, Hummel HD, Borghaei H, Johnson ML, Steeghs N, Blackhall F, Dowlati A, Reguart N, Yoshida T, He K, Gadgeel SM, Felip E, Zhang Y, Pati A, Minocha M, Mukherjee S, Goldrick A, Nagorsen D, Hashemi Sadraei N, Owonikoko TK. Tarlatamab, a First-in-Class DLL3-Targeted Bispecific T-Cell Engager, in Recurrent Small-Cell Lung Cancer: An Open-Label, Phase I Study. J Clin Oncol. 2023 Jun 1;41(16):2893-2903. doi: 10.1200/JCO.22.02823. Epub 2023 Jan 23.

  PMID: 36689692 BACKGROUND

• Megyesfalvi Z, Gay CM, Popper H, Pirker R, Ostoros G, Heeke S, Lang C, Hoetzenecker K, Schwendenwein A, Boettiger K, Bunn PA Jr, Renyi-Vamos F, Schelch K, Prosch H, Byers LA, Hirsch FR, Dome B. Clinical insights into small cell lung cancer: Tumor heterogeneity, diagnosis, therapy, and future directions. CA Cancer J Clin. 2023 Nov-Dec;73(6):620-652. doi: 10.3322/caac.21785. Epub 2023 Jun 17.

  PMID: 37329269 BACKGROUND

• Rojo F, Corassa M, Mavroudis D, Oz AB, Biesma B, Brcic L, Pauwels P, Sailer V, Gosney J, Miljkovic D, Hader C, Wu M, Almarez T, Penault-Llorca F. International real-world study of DLL3 expression in patients with small cell lung cancer. Lung Cancer. 2020 Sep;147:237-243. doi: 10.1016/j.lungcan.2020.07.026. Epub 2020 Jul 27.

  PMID: 32745892 BACKGROUND

• Jaspers JE, Khan JF, Godfrey WD, Lopez AV, Ciampricotti M, Rudin CM, Brentjens RJ. IL-18-secreting CAR T cells targeting DLL3 are highly effective in small cell lung cancer models. J Clin Invest. 2023 May 1;133(9):e166028. doi: 10.1172/JCI166028.

  PMID: 36951942 BACKGROUND

• Zhang Y, Tacheva-Grigorova SK, Sutton J, Melton Z, Mak YSL, Lay C, Smith BA, Sai T, Van Blarcom T, Sasu BJ, Panowski SH. Allogeneic CAR T Cells Targeting DLL3 Are Efficacious and Safe in Preclinical Models of Small Cell Lung Cancer. Clin Cancer Res. 2023 Mar 1;29(5):971-985. doi: 10.1158/1078-0432.CCR-22-2293.

  PMID: 36692420 BACKGROUND

• Zhou D, Byers LA, Sable B, Smit MD, Sadraei NH, Dutta S, Upreti VV. Clinical Pharmacology Profile of AMG 119, the First Chimeric Antigen Receptor T (CAR-T) Cell Therapy Targeting Delta-Like Ligand 3 (DLL3), in Patients with Relapsed/Refractory Small Cell Lung Cancer (SCLC). J Clin Pharmacol. 2024 Mar;64(3):362-370. doi: 10.1002/jcph.2346. Epub 2023 Oct 2.

  PMID: 37694295 BACKGROUND

• Owen DH, Giffin MJ, Bailis JM, Smit MD, Carbone DP, He K. DLL3: an emerging target in small cell lung cancer. J Hematol Oncol. 2019 Jun 18;12(1):61. doi: 10.1186/s13045-019-0745-2.

  PMID: 31215500 BACKGROUND

Study Officials

• You Lu, MD

  West China Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jianxin Xue, MD

CONTACT

18982251798; killercell@163.com

Zhuoran Yao, MD

CONTACT

13261660839; yaozhuoran@outlook.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chair of Department of Thoracic Cancer

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: April 5, 2024
• Study Start: April 3, 2025
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: May 16, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)