Table 8 Nanobodies in clinical trials
Clinical trial ID/ Phase | Title | Study design | Eligibility criteria | Intervention | Primary outcome measures | Secondary outcome measures | Results | References |
|---|---|---|---|---|---|---|---|---|
NCT05639153/ Phase I | A Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Preliminary Efficacy of DR30303 in Patients With Advanced Solid Tumors | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with advanced solid tumors | DR30303-a recombinant humanized monoclonal antibody that targets Claudin18.2 | Safety and tolerability of DR30303, including incidence and severity of adverse events | Objective response rate (ORR), Progression-free survival PFS, OS (RECIST 1.1) | Completion date- 30/04/2024 | [242] |
NCT03972150/ Phase I | A Study to Find the Best Dose of BI 836880 Alone and in Combination With BI 754091 in Japanese Patients With Different Types of Advanced Cancer | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with advanced solid tumors | BI 836880 BI 754091 | Maximum tolerated dose (MTD) and/or recommended Phase 2 dose (RP2D) of BI 836880 alone and in combination with BI 754091 | Objective response rate (ORR) and disease control rate (DCR) | Maximum tolerated dose was not reached. BI 836880 alone and in combination with ezabenlimab had a manageable safety profile with preliminary clinical activity in Japanese patients with advanced solid tumors | [243] |
NCT03248843/ Phase I | A Study of PD-L1 Antibody KN035 in Japanese Subjects With Locally Advanced or Metastatic Solid Tumors | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with advanced solid tumors | Single-domain anti-PD-L1 monoclonal antibody KN035 | Safety and tolerability of KN035, including incidence and severity of adverse events | Objective response rate (ORR) and disease control rate (DCR) | Well tolerated with efficacy. Pharmacokinetics data and preliminary anti-tumor response support dose regimens | [244] |
NCT03667170/ Phase I | KN035 in Subjects With Advanced Solid Tumors | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with advanced solid tumors | Single-domain anti-PD-L1 monoclonal antibody KN035 | Objective response rate (ORR) and disease control rate (DCR) | Duration of response (DOR), Progression-free survival (PFS), Overall survival (OS) | Completion date- 15/12/2025 | [245] |
NCT02827968/ Phase I | Phase 1 Study of Anti-PD-L1 Monoclonal Antibody KN035 to Treat Locally Advanced or Metastatic Solid Tumors | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with advanced solid tumors | Single-domain anti-PD-L1 monoclonal antibody KN035 | Incidence of dose limiting toxicities (DLTs) Percentage of participants with adverse events (AEs), serious adverse events and AEs of special interest | Duration of response (DOR), Progression-free survival (PFS), Overall survival (OS) | Favorable safety and pharmacokinetic profile, with promising preliminary antitumor activity in patients with advanced solid tumors | [246] |
NCT02683083/ Phase I | [131I]-SGMIB Anti-HER2 VHH1 in Patients With HER2 + Breast Cancer | Interventional, Single Group Assignment, Open Label, Safety Study | Female patients with HER2 + breast cancer | [131I]-SGMIB Anti-HER2 VHH1 | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 | Tumor targeting potential will be visually scored on the planar total body scan | No drug-related adverse events with 131I-GMIB-anti-HER2-VHH1, primarily eliminated through the kidneys, stability in circulation, exhibited specific uptake in metastatic lesions in advanced breast cancer patients | [247] |
NCT02340208/ Phase I/II | A Phase I/​II Open-Label, Non-Randomized Dose Escalation Study of Immunoconjugate L-DOS47 | Interventional, Open Label, Safety Study | Adults with histologically or cytologically confirmed nonsquamous NSCLC | Urease conjugated to a camelid monoclonal antibody- L DOS47 | The incidence and severity of drug-related adverse events as a measure of safety and tolerability of L-DOS47 | L-DOS47 related toxicity during the first 2 h after infusion, incidence and severity of all reported adverse events and serious adverse events | One dose-limiting toxicity (spinal pain) observed, no complete or partial responses were seen, 32 patients achieved stable disease after two treatment cycles, one patient in cohort 9 remained on treatment for 10 cycles without disease progression | [248] |
NCT02309892/ Phase I | A Phase I, Open Label, Dose Escalation Study of Immunoconjugate L-DOS47 in Combination With Pemetrexed/Carboplatin in Patients With Stage IV (TNM M1a and M1b) Recurrent or Metastatic NSCL Lung Cancer | Interventional, Single Group Assignment, Open Label, Safety Study | Adults with histologically or cytologically confirmed nonsquamous NSCLC | L-DOS47 | Number of patients with adverse events as a measure safety and tolerability of L-DOS47 in combination treatment with pemetrexed/carboplatin | ORR | L-DOS47 combined with standard pemetrexed and carboplatin chemotherapy is well tolerated in patients with recurrent or metastatic nonsquamous NSCLC | [249] |
NCT04887259/ Phase I/IIa | Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML | Interventional, Sequential Assignment, Open Label, Treatment | Adults with relapsed or refractory CLL, MM, or AML | Bispecific gamma-Delta T-Cell engager-LAVA-051 | Frequency and severity of AEs, Frequency and type of DLT | Number of participants with an antitumor response, Pharmacokinetics of LAVA-051, area under the plasma concentration versus time curve (AUC) | Completion – 30/12/2024 | [250] |
NCT05369000/ Phase I/IIa | Trial of LAVA-1207 in Patients With Therapy Refractory Metastatic Castration Resistant Prostate Cancer | Interventional, Sequential Assignment, Open Label, Treatment | Male patients 18 years and older with metastatic castration resistant prostate cancer | Humanized bispecific antibody of two single domain antibody (VHH)-LAVA-1207 | Frequency and severity of Adverse Events (AEs), Frequency and type of Dose-Limiting Toxicity (DLT) | Objective response rate (ORR), Duration of response (DOR), Progression-free survival (PFS) | Completion—30/03/2024 | [251] |
NCT03548207/ Phase Ib/2 | A Phase 1b-2, Open-Label Study of JNJ-68284528, A Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Relapsed or Refractory Multiple Myeloma | Single Group Assignment, Open Label | Adults with multiple myeloma | A Chimeric Antigen Receptor T-Cell—JNJ-68284528 | Phase 1b: Number of Participants with Adverse Events; Number of Participants with Adverse Events by Severity; Phase 2: Overall Response Rate (ORR) | Levels of B-Cell Maturation Antigen (BCMA) Expressing Cells and Soluble BCMA, Level of JNJ-68284528 T-Cell Expansion (proliferation), and Persistence, Levels of CAR-T Cells | With a median follow-up of 18 months, results show significant, long-lasting responses in heavily treated multiple myeloma patients, the treatment maintained a manageable safety profile without any new safety concerns | |
NCT03090659/ Phase 1/2 | A Clinical Study of Legend Biotech BCMA-chimeric Antigen Receptor Technology in Treating Relapsed/Refractory (R/R) Multiple Myeloma Patients | Single Group Assignment, Open Label | Patients with refractory multiple myeloma. Clear BCMA expression must be detected on malignant plasma cells from either bone marrow or a plasmacytoma by flow cytometry or immunohistochemistry | LCAR-B38M CAR-T-cell injection | Occurrence of treatment related adverse events as assessed by CTCAE v4.0 | Anti-myeloma responses to LCAR-B38M cell treatment | Completion-31/12/2023 | [254] |
NCT04133636/ Phase 2 | A Phase 2, Multicohort Open-Label Study of JNJ-68284528, a Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Directed Against BCMA in Subjects With Multiple Myeloma | Single Group Assignment, Open Label | Adults with multiple myeloma | A Chimeric Antigen Receptor T-Cell—JNJ-68284528 | Percentage of Participants with Negative Minimal Residual Disease (MRD), Percentage of Participants with Sustained MRD Negative Complete Response (CR) | Overall Response Rate (ORR), Duration of Response (DOR) | Completion-13/11/2028 Interim results—responses with manageable safety, responses in pts with ineffective or insufficient response to autologous stem cell transplantation | |
NCT03924466/ Phase II | Quantification of 68-GaNOTA-Anti-HER2 VHH1 Uptake in Metastasis of Breast Carcinoma Patients and Assessment of Repeatability (VUBAR)—Pilot Study | Single Group Assignment, Open Label | Patients with locally advanced or metastatic breast cancer | 68GaNOTA-Anti-HER2 VHH1 | Repeatability of lesional PET/CT characteristics, Tracer update of 68GaNOTA-Anti-HER2 VHH1 in different cancer types, Feasibility and added value of 68GaNOTA-Anti-HER2 in neoadjuvant setting of breast carcinoma | Within-patient tumor heterogeneity for HER2 expression using PET/CT imaging, Immunogenicity, Histopathological results of biopsied lesions and correlation with PET/CT results | Completion-31/12/2024 | [259] |
NCT05556096/ Phase III | A Phase 3, Randomized, Double-blind, Placebo-controlled, Parallel, Multicenter Study to Evaluate the Safety and Efficacy of ALXN1720 in Adults With Generalized Myasthenia Gravis | Double-blind, randomized | Diagnosis of MG with generalized muscle weakness | ALXN1720 | Change From Baseline in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Total Score at Week 26 | Change From Baseline in Quantitative Myasthenia Gravis (QMG) Total Score at Week 26, Percentage of Responders Based on Reduction of the MG-ADL Total Score at Week 26 | Completion-07/07/2027 | [260] |