TABLE 2.
Small molecules targeting Notch signaling and their clinical trials.
| Compound | Tumor type | Phase (Clinicaltrials.gov identifier) | Efficacy outcomes | Status | References |
|---|---|---|---|---|---|
| MK‐0752 | T‐ALL and AML | Phase I (NCT00100152) | 1 patient with T‐ALL had a 45% reduction in a mediastinal mass | Discontinued | 382 |
| MK‐0752 with gemcitabine | Unresectable PDAC | Phase I (NCT01098344) | 47% patients had SD (9 of 19); PRs: 5% patients (1 of 19) | Discontinued | 383 |
| MK‐0752 followed by docetaxel | Advanced‐stage breast cancer | Phase I/II (NCT00645333) | Not reported | Discontinued | 384 |
| MK‐0752 with ridaforolimus | Advanced‐stage solid tumors | Phase I (NCT01295632) | 11% patients (2 of 18) with HNSCC had responses; 1 patient had SD lasting ≥6 months | Discontinued | 385 |
| PF‐03084014 | Advanced‐stage solid tumors | Phase I (NCT00878189) | CR: 2% evaluable patients (1 of 46; thyroid cancer); PRs: 11% patients (5 of 46; all desmoid tumors); 30% patients had SD (14 of 46) | Clinical studies ongoing | 386 |
| PF‐03084014 | Advanced‐stage TNBC | Phase II (NCT02299635) | Not reported | Clinical studies ongoing | 387 |
| PF‐03084014 | T‐ALL or T‐LBL | Phase I (NCT00878189) | CR: 12.5% patients (1 of 8) | Clinical studies ongoing | 388 |
| PF‐03084014 | Desmoid tumors | Phase II (NCT01981551) | PR: 29% patients (5 of 16); 29% patients had SD (5 of 16) | Clinical studies ongoing | 389 |
| PF‐03084014 with gemcitabine and nab‐paclitaxel | Metastatic PDAC | Phase Ib/II (NCT02109445) | ORR: 0% | Clinical studies ongoing | |
| RO4929097 | Metastatic CRC | Phase II (NCT01116687) | 18.2% evaluable patients had SD (6 of 33); Median OS: 6.0 months; Median PFS: 1.8 months | Discontinued | 390 |
| RO4929097 with gemcitabine | Advanced‐stage solid tumors | Phase I | PR: 5.6% patient with nasopharyngeal carcinoma; 3 patients had SD | Discontinued | 391 |
| RO4929097 with temsirolimus | Advanced‐stage solid tumors | Phase Ib (NCT01198184) | 73% patients had SD | Discontinued | 392 |
| BMS‐906024 | T‐ALL | Phase I | (32%) patients (8) had ≥50% reduction in bone marrow blasts | Clinical studies ongoing | 393 |
| Brontictuzumab | Hematological malignancies | Phase I | PR in 4.3% patient with TMF (1); 8.7% patients had SD in (2) | No phase II or III trials ongoing; discontinued in hematological malignancies | 394 |
| Tarextumab or placebo with gemcitabine and nab‐paclitaxel | Metastatic PDAC | Phase Ib/II (NCT01647828) | Placebo vs. tarextumab arms: Median OS: 7.9 months vs. 6.4 months Median PFS: 5.5 months vs. 3.7 months; ORR: 31.8 vs. 20.2% | Discontinued | 395 |
| Tarextumab or placebo with etoposide and cisplatin | Extensive‐stage SCLC | Phase Ib/II (NCT01859741) | ORR in 84% patients of phase Ib part; placebo vs. tarextumab arms in phase II part: Median PFS: 10.3 months vs. 9.3 months; ORR: 70.8 vs. 68.5%; | Discontinued | 396 |
| Demcizumab or placebo with carboplatin and pemetrexed | Metastatic nonsquamous NSCLC | Phase I (NCT01189968) | 3% patients had CR patients (1 of 40); 48% patients had PR (19 of 40); 38% patients had SD (15 of 40) | Progressed to the randomized phase II study (NCT02259582) | 397 |
|
Demcizumab with gemcitabine, with or without nab‐paclitaxel |
Advanced‐stage PDAC | Phase Ib (NCT01189929) | 50% evaluable patients had PR (14 of 28); 39.3% patients had SD (11 of 28); Median OS: 10.1 months; Median PFS: 9.0 months | Progressed to the randomized phase II study (NCT02289898) | 398 |
| Rovalpituzumab tesirine | SCLC | Phase I (NCT01901653) | 17% patients had PR or CR (11 of 65 patients); 54% patients had SD (35 of 65); Median OS: 4.6 months; Median PFS: 3.1 months | Progressed to the phase II study (NCT02674568) | 377 |
Abbreviations: AML, acute myeloid leukemia; CR, complete response; CRC, colorectal cancer; DoR, duration of response; HNSCC, head and neck squamous cell carcinoma; n, number of patients; NSCLC, non‐small cell lung cancer; ORR, objective response rate; OS, overall survival; PDAC, pancreatic adenocarcinoma; PFS, progression‐free survival; PR, partial response; SCLC, small‐cell lung cancer; SD, stable disease; T‐ALL, T‐cell acute lymphocytic leukemia; T‐LBL, T‐cell lymphoblastic lymphoma; TMF, transformed mycosis fungoides; TNBC, triple‐negative breast cancer.