From: The Notch signaling pathway: a potential target for cancer immunotherapy
Drug Name | Class | Identifier/Refs; Phase | Cancer | First posted; Status; Country | Results |
---|---|---|---|---|---|
Curcumin | SERCA inhibitor | NCT00094445 [26];II | Pancreatic cancer | 2004; Completed; USA | 25 patients took curcumin orally, 21 patients evaluable for response, and 2 patients had clinical biological activity. Among them, 1 patient remained stable condition > 18 months, another patient experienced transient but significant 73% tumor regression |
CRC | 2011; Completed; United Kingdom | Based on the FOLFOX chemotherapy measure, daily oral curcumin is safe and tolerable in CRC patients | |||
NCT02064673; III | PCa | 2014; Recruiting; USA | Ongoing | ||
OMP-52M51 (Brontictuzumab) | Anti-Notch1 mAb | NCT01703572 [29]; I | Lymphoid malignancies | 2012; Completed; USA | In 24 assessable patients, OMP-52M51 treatment was generally well tolerated, and exhibited moderate anti-tumor activity with one PR and two SD. However, diarrhea was the main side effect of OMP-52M51 |
NCT01778439 [30]; I | Solid tumor | 2013; Completed; USA | Clinical benefit was seen in 6 of 36 (17%) assessable patients, 2 patients had PR and 4 patients had prolonged (≥ 6 months) SD. OMP-52M51 treatment was well tolerated in patients, and diarrhea was the main toxicity | ||
NCT02662608 [31]; I | ACC | 2016; Completed; USA | Only 1 ACC patient with Notch1-mutant received OMP-52M51 treatment, and this patient had PR | ||
NCT03031691; I | Metastatic CRC | 2017; Completed; USA | Unpublished | ||
OMP-59R5 | Anti-Notch2/3 mAb | NCT01277146 [32]; I | Solid tumor | 2011; Completed; USA | Among 42 patients, three strategies of OMP-59R5 treatment (weekly dose < 2.5 mg/kg, every other or every third week dose 7.5 mg/kg) were well tolerated. The most common AE was GI toxicity, including diarrhea (81%), fatigue (48%), nausea (45%), anorexia (38%), vomiting (38%) and abdominal pain and constipation (24% each) |
NCT01647828 [33]; I/II | Stage IV pancreatic cancer | 2012; Completed; USA | In metastatic PDAC, first-line drugs (e.g., nab-paclitaxel and gemcitabine) combined with OMP-59R5 did not improve OS, PFS, or ORR. PFS was specifically statistically worse in OMP-59R5-treated patients | ||
NCT01859741; I/II | Stage IV SCLC | 2013; Terminated; USA | Terminated due to unimproved PFS | ||
Rovalpituzumab tesirine (Rova-T) | Anti-Dll3 mAb | NCT01901653 [36]; I/II | Recurrent SCLC | 2013; Completed; USA | 82 patients received at least one dose of Rova-T. 11 of 60 (18%) assessable patients had a confirmed objective response, including 10 of 26 (38%) Dll3-high patients. Drug-related serious AEs occurred in 28 of 74 (38%) patients. Rova-T treatment showed encouraging single-agent anti-tumor activity with a manageable safety profile |
NCT02874664 [34]; I | SCLC | 2016; Completed; USA | 46 patients received at least one dose of Rova-T treatment. After administration of Rova-T, there were no clinically changes in QRS or PR intervals, electrocardiogram waveforms, or heart rate | ||
NCT02674568 [35]; II | SCLC | 2016; Completed; USA, France | In 339 patients, ORR was 12.4%, 14.3%, and 13.2% in all, Dll3-high, and Dll3-positive patients, respectively. Median OS was 5.6 months in all patients, and 5.7 months in Dll3-high patients. The most common AEs were fatigue, photosensitivity reaction, and pleural effusion | ||
Rovalpituzumab tesirine (Rova-T) | Anti-Dll3 mAb | NCT02709889 [40]; I/II | MCC | 2016; Terminated; USA | In 65 patients, 1 MCC patient with Dll3‐high expression was treated with Rova-T and achieved partial positive response |
NCT02819999 [37]; I | SCLC | 2016; Terminated; USA | Patients who received both Rova-T and platinum-based chemotherapy did not have better therapeutic benefits than patients who received platinum-based chemotherapy alone | ||
NCT03086239 [42]; I | SCLC | 2017; Completed; Japan | In 29 Japanese patients, Rova-T treatment exhibited manageable toxicity. In Dll3-high expression patients, 3 of 18 (17%) patients had confirmed PR. The disease control rate was 56%, median PFS was 2.9 months, and median OS was 7.4 months | ||
NCT03026166 [38]; I/II | SCLC | 2017; Terminated; USA | Rova-T in combination with other chemotherapy drugs were not well tolerable in SCLC patients | ||
NCT03061812 [39]; III | SCLC | 2017; Completed; USA | Compared with topotecan treatment patients, patients who received Rova-T treatment exhibited an inferior OS, higher rates of serosal effusions, photosensitivity reaction, and peripheral edema | ||
NCT03543358; II | Cancer | 2018; Completed; USA | Unpublished | ||
SC-002 | Anti-Dll3 mAb | NCT02500914 [41]; I | SCLC | 2015; Terminated; USA | In 35 enrolled patients received ≥ 1 dose of SC-002 treatment, 23 patients experienced serious AEs, 5 patients achieved a PR, and no patients achieved a complete response |
MEDI0639 | Anti-Dll4 mAb | NCT01577745 [43]; I | Solid tumor | 2012; Completed; USA | In 20 patients, 1 melanoma patient had PRs, and 7 patients had stable disease lasting ≥ 12 weeks. The most common TrAEs were increased aspartate aminotransferase, increased BNP, and fatigue. No treatment-related deaths occurred |
Demcizumab | Anti-Dll4 mAb | NCT01189968 [44]; I | NSCLC | 2010; Completed; Australia | 46 treatment-naive NSCLC patients were enrolled. After treatment of demcizumab, 20 of 40 (50%) evaluable patients had objective tumor responses. The common AEs of patients were hypertension and raised brain natriuretic peptide |
NCT01189929; I | Pancreatic cancer | 2010; Completed; Australia | Unpublished | ||
NCT01952249[45]; I | Primary peritoneal carcinoma | 2013; Terminated; USA | In 19 patients who were enrolled, no DLT was observed. ORR was 21%. The most common TEAE were diarrhea (68%), fatigue (58%), peripheral edema (53%), and nausea (53%) | ||
NCT02259582; II | NSCLC | 2014; Completed; USA | Unpublished | ||
NCT02289898; II | Pancreatic cancer | 2014; Completed; USA | Unpublished | ||
NCT02722954 [46]; I | Advanced or metastatic solid tumor | 2016; Completed; USA | In 27 patients, 1 patient was observed PR and 8 patients had stable disease. Demcizumab plus pembrolizumab were well tolerated in patients. However, there is no evidence to suggest that demcizumab has significant anti-tumor activity after treatment | ||
INCB7839 (Aderbasib) | ADAM inhibitor | NCT04295759; I | High-grade gliomas | 2020; Recruiting; USA | Ongoing |
MK0752 | γ-secretase inhibitor | NCT00100152; I | Leukemia | 2004; Terminated; Unknown | Mediastinal masses decreased by 45% in 1/6 (16%) of patients; the study was discontinued due to severe diarrhea |
MK0752 | γ-secretase inhibitor | NCT00106145 [47]; I | Advanced BC or other solid tumor | 2005; Completed; USA | 103 patients received MK0752 treatment. Among patients with high-grade gliomas, 1 patient complete response and an additional 10 patients with stable disease > 4 months. The most common drug-related toxicities were diarrhea, nausea, vomiting, and fatigue |
NCT00645333 [48]; I/II | Metastatic BC | 2008; Completed; USA | 30 patients were treated with docetaxel plus escalating doses of MK0752. In tumors of patients undergoing serial biopsies, a decrease in BC stem cell markers (CD44+/CD24−, ALDH+) and mammosphere-forming efficiency was observed | ||
NCT01098344 [49]; I | Pancreatic cancer | 2010; Completed; United Kingdom | 44 eligible patients received MK0752 treatment with/without gemcitabine. Tumor response evaluation was available in 19 patients, 13 patients achieved stable disease, and 1 patient achieved a confirmed PR. MK0752 can combine with gemcitabine or as single-agent | ||
LY900009 | γ-secretase inhibitor | NCT01158404 [53]; I | Advanced cancer | 2010; Completed; USA | In 35 patients who received LY900009, study drug-related AEs were diarrhea (46%), vomiting (34%), anorexia (31%), nausea (31%), and fatigue (23%) |
PF-03084014 | γ-secretase inhibitor | NCT02299635; II | TNBC | 2014; Terminated; USA | SAEs 6/19; early termination of research due to project sponsors' reprioritization |
AL101 | γ-secretase inhibitor | NCT04461600; II | TNBC | 2020; Active, not recruiting; USA | Ongoing |
NCT04973683; I | Adenoid cystic cancer | 2021; Recruiting; USA | Ongoing | ||
RO4929097 | γ-secretase inhibitor | NCT01071564; I | BC | 2010; Terminated; USA | Patients experienced life-threatening complications (e.g., arrhythmia) after treatment. Therefore, the clinical trial was terminated |
NCT01154452 [50]; I | Advanced or metastatic sarcoma | 2010; Completed; USA | The combination of RO4929097 plus vismodegib was generally well tolerated. However, the combination did not meaningfully enhance the clinical efficacy | ||
NCT01196416; I/II | Recurrent or metastatic melanoma | 2010; Completed; USA | Unpublished | ||
NCT01120275 [51]; II | Malignant melanoma | 2010; Terminated; USA | In 32 evaluable patients, RO4929097 treatment was well tolerated. Specifically, 1 patient with confirmed PR lasting 7 months, another 8 patients with stable disease > 12 weeks, and 1 patient with stable disease > 31 months. The 6-month PFS rate was 9%, and the 1-year OS rate was 50%. The most common toxicities were nausea (53%), fatigue (41%), and anemia (22%) | ||
NCT01198184 [52]; I | Advanced solid tumor | 2010; Completed; Canada | In order to evaluate the safety, PKs and pharmacodynamics of RO4929097 combined with temsirolimus, 17 patients were enrolled. 11 patients had stable disease. The most common toxicities included: fatigue (82%; grade 36%), mucositis, (71%;), neutropenia (59%), anemia (59%), and hypertriglyceridemia (59%) | ||
NCT01218620; I | Adult solid neoplasm | 2010; Completed; USA | Unpublished | ||
LY3039478 | γ-secretase inhibitor | NCT02836600 [56]; I | Advanced solid tumor | 2016; Active, not recruiting; Japan | In 11 enrolled Japanese patients, no dose-limiting toxicities or dose-limiting equivalent toxicities were observed. 1 patient (14.3%) with a desmoid tumor showed tumor size shrinkage of 22.4% and had stable disease for 22.5 months. The TrAEs are diarrhea, malaise, and vomiting |
Solid tumor | 2016; Completed; USA, Spain Denmark, France, | LY3039478 combined with different anticancer agents (gemcitabine, cisplatin, and carboplatin) was poorly tolerated | |||
CB-103 | Notch transcription complex inhibitor | NCT03422679; I/II | Advanced solid tumors; hematological malignancies | 2018; Terminated; USA | CB-103 was effective to control the Notch transcription complex, and is tolerable in patients with advanced tumors |