Table 4. Ongoing clinical trials testing new combinations with CDK4/6-inhibitors.
HR+, hormone receptor-positive; LHRH, luteinizing hormone-releasing hormone; ER+, estrogen receptor-positive; PD-1, programmed cell death protein 1; PD-L1, programmed cell death 1 ligand 1; AR+, androgen receptor-positive; TNBC, triple-negative breast cancer; EGFR, epidermal growth factor receptor; HER2+, human epidermal growth factor receptor 2-positive; FGFR, fibroblast growth factor receptor; IGFR, insulin-like growth factor receptor; VEGF, vascular endothelial growth factor receptor; PI3K, phosphoinositide 3-kinase; NSCLC, non-small cell lung cancer; ALL, acute lymphoblastic leukemia; SCLC, small cell lung cancer.
| CDK4/6 inhibitor | Additional target | Inhibitor | Immune checkpoint inhibitor | Tumor type | Trial identifier |
|---|---|---|---|---|---|
| Palbociclib | aromatase | letrozole, anastrozole, exemestane | HR+ breast cancer, HR+ ovarian cancer, metastatic breast cancer, metastatic endometrial cancer |
NCT04130152; NCT03054363; NCT03936270; NCT04047758; NCT02692755; NCT02806050; NCT03870919; NCT02040857; NCT04176354; NCT02028507; NCT03220178; NCT02592083; NCT02603679; NCT04256941; NCT03425838; NCT02894398; NCT02297438; NCT02730429; NCT02142868; NCT02942355 |
|
| LHRH | LHRH agonists: goserelin, leuprolide | HR+ breast cancer |
NCT03969121; NCT03423199; NCT01723774; NCT02917005; NCT02592746; NCT03628066 |
||
| ER | ER-antagonists: fulvestrant, tamoxifen | HR+ breast cancer, metastatic breast cancer |
NCT02668666; NCT02738866; NCT03184090; NCT04526028; NCT02513394; NCT03560856; NCT02760030; NCT03079011; NCT03227328; NCT03809988; NCT02764541; NCT03007979; NCT03633331 |
||
| ER | selective estrogen receptor degraders (SERD): G1T48, ZN-c5, SAR439859, AZD9833, GDC-9545 | HR+ breast cancer |
NCT03455270; NCT04546009; NCT04436744; NCT04478266; NCT03560531; NCT03616587; NCT03284957; NCT03332797 |
||
| ER | selective estrogen receptor modulator (SERM): bazedoxifene | HR+ breast cancer |
NCT03820830; NCT02448771 |
||
| aromatase + PD-1 | letrozole, anastrozole | pembrolizumab, nivolumab | stage IV ER+ breast cancer | NCT02778685; NCT04075604 | |
| PD-1 | nivolumab, pembrolizumab, MGA012 | liposarcoma | NCT04438824 | ||
| PD-L1 | Avelumab | AR+ breast cancer, TNBC, ER+/HER2-metastatic breast cancer |
NCT04360941; NCT03147287 |
||
| EGFR + PD-L1 | cetuximab | Avelumab | squamous cell carcinoma of the head and neck | NCT03498378 | |
| HER2 | tucatinib, trastuzumab, pertuzumab, T-DM1, ZW25 | HER2+ breast cancer |
NCT03530696; NCT03054363; NCT02448420; NCT03709082; NCT03304080; NCT02947685 |
||
| EGFR/HER2 | neratinib | advanced solid tumors with EGFR mutation/amplification, HER2 mutation/amplification, HER3/4 mutation, or KRAS mutation |
NCT03065387 | ||
| EGFR | cetuximab | metastatic colorectal cancer, squamous cell carcinoma of the head and neck |
NCT03446157; NCT02499120 |
||
| FGFR | erdafitinib | ER+/HER2-/FGFR-amplified metastatic breast cancer | NCT03238196 | ||
| FGFR1–3 | rogaratinib | FGFR1–3+/HR+ breast cancer | NCT04483505 | ||
| IGF-1R | ganitumab | Ewing sarcoma | NCT04129151 | ||
| VEGF1–3 receptors + PD-L1 | axitinib | Avelumab | NSCLC | NCT03386929 | |
| RAF | sorafenib | leukemia | NCT03132454 | ||
| MEK | PD-0325901, binimetinib | KRAS mutant NSCLC, TNB, KRAS and NRAS mutant metastatic or unresectable colorectal cancer |
NCT02022982; NCT03170206; NCT04494958; NCT03981614 |
||
| ERK | ulixertinib | advanced pancreatic and other solid tumors | NCT03454035 | ||
| PI3K | copanlisib | HR+ breast cancer | NCT03128619 | ||
| PI3K | taselisib, pictilisib, GDC-0077 | PIK3CA mutant advanced solid tumors, PIK3CA mutant and HR+ breast cancer |
NCT02389842; NCT04191499; NCT03006172 |
||
| PI3K/mTOR | gedatolisib | metastatic breast cancer, advanced squamous cell lung, pancreatic, head & neck cancer and other solid tumors |
NCT02684032; NCT03065062; NCT02626507 |
||
| mTOR | everolimus, vistusertib | HR+ breast cancer | NCT02871791 | ||
| AKT | ipatasertib | HR+ breast cancer, metastatic breast cancer, metastatic gastro-intestinal tumors, NSCLC |
NCT03959891; NCT04060862; NCT04591431 |
||
| BTK | ibrutinib | mantle cell lymphoma | NCT03478514 | ||
| BCL-2 | venetoclax | ER+/BCL-2+ advanced or metastatic breast cancer | NCT03900884 | ||
| AR | AR-antagonists: bicalutamide | AR+ metastatic breast cancer | NCT02605486 | ||
| lysosome + aromatase | hydroxychloroqu ine + letrozole | ER+ breast cancer | NCT03774472 | ||
| proliferating cells | standard chemotherapy | stage IV ER+ breast cancer | NCT03355157 | ||
| proliferating cells | radiation | stage IV ER+ breast cancer |
NCT03870919; NCT03691493; NCT04605562 |
||
| BCR-ABL | bosutinib | HR+ breast cancer | NCT03854903 | ||
| Ribociclib | aromatase | letrozole, anastrozole, exemestane | HR+ breast cancer, metastatic breast cancer, ovarian cancer |
NCT04256941; NCT03425838; NCT03822468; NCT02712723; NCT03673124; NCT02941926; NCT03248427; NCT03671330; NCT02333370; NCT01958021; NCT03425838; |
|
| LHRH | LHRH agonists: goserelin, leuprolide | HR+ breast cancer | NCT03944434 | ||
| ER | ER-antagonists: fulvestrant | HR+ breast cancer, advanced breast cancer |
NCT03227328; NCT02632045; NCT02632045; NCT03555877 |
||
| PD-1 | spartalizumab | breast cancer and ovarian cancer, recurrent and/or metastatic head and neck squamous cell carcinoma, melanoma |
NCT03294694; NCT04213404; NCT03484923 |
||
| HER2 | trastuzumab, pertuzumab, T-DM1 | HER2+ breast cancer |
NCT03913234; NCT02657343 |
||
| EGFR | nazartinib (EGF816) | EGFR mutant NSCLC | NCT03333343 | ||
| RAF | encorafenib, LXH254 | NSCLC, BRAF mutant melanoma | NCT02974725; NCT03333343; NCT04417621; NCT02159066 | ||
| MEK | binimetinib | BRAF V600-dependent advanced solid tumors, melanoma | NCT01543698; NCT02159066 | ||
| PI3K | alpelisib | breast cancer with PIK3CA mutation | NCT03439046 | ||
| mTOR | everolimus | advanced dedifferentiated liposarcoma, leiomyosarcoma, glioma, astrocytoma, glioblastoma, endometrial carcinoma, pancreatic cancer, neuroendocrine tumors |
NCT03114527; NCT03355794; NCT03834740; NCT03008408; NCT02985125; NCT03070301 |
||
| mTOR + inflammation | everolimus + dexamethasone | ALL | NCT03740334 | ||
| SHP2 | TNO155 | advanced solid tumors | NCT04000529 | ||
| AR | AR-antagonists: bicalutamide, enzalutamide | TNBC, metastatic prostate carcinoma |
NCT03090165; NCT02555189 |
||
| HDAC | belinostat | TNBC, ovarian cancer | NCT04315233 | ||
| proliferating cells | standard chemotherapy | ovarian cancer, metastatic solid tumors, soft tissue sarcoma, hepatocellular carcinoma |
NCT03056833; NCT03237390; NCT03009201; NCT02524119 |
||
| Abemaciclib | aromatase | letrozole, anastrozole, exemestane | HR+ breast cancer, metastatic breast cancer, endometrial cancer |
NCT04256941; NCT03425838; NCT04227327; NCT04393285; NCT04305236; NCT03643510; NCT03675893; NCT04352777; NCT04293393; NCT02057133 |
|
| ER | ER-antagonists: fulvestrant | advanced breast cancer, low-grade serous ovarian cancer | NCT03227328; NCT03531645; NCT04158362; NCT01394016 | ||
| PD-1 | nivolumab, pembrolizumab | head and neck cancer, gastroesophageal cancer, nScLC, HR+ breast cancer |
NCT04169074; NCT03655444; NCT03997448; NCT02779751 |
||
| ER + PD-L1 | ER-antagonists: fulvestrant |
atezolizumab | HR+ breast cancer, metastatic breast cancer | NCT03280563 | |
| AKT + ER + PD-L1 | ipatasertib + ER-antagonists fulvestrant |
atezolizumab | HR+ breast cancer | NCT03280563 | |
| PD-L1 | LY3300054 | advanced solid tumors | NCT02791334 | ||
| HER2 | trastuzumab | HER2+ metastatic breast cancer | NCT04351230 | ||
| receptor tyrosine kinases |
sunitinib | metastatic renal cell carcinoma | NCT03905889 | ||
| IGF-1/IGF-2 | xentuzumab | HR+ breast cancer | NCT03099174 | ||
| VEGF-A | bevacizumab | Glioblastoma | NCT04074785 | ||
| PI3K | copanlisib | HR+ breast cancer, metastatic breast cancer | NCT03939897 | ||
| PI3K/mTOR | LY3023414 | metastatic cancer | NCT01655225 | ||
| ERK1/2 | LY3214996 | tumors with ERK1/2 mutations, glioblastoma, metastatic cancer |
NCT04534283; NCT04391595; NCT02857270 |
||
| Trilaciclib | proliferating cells |
chemotherapy | SCLC. This trial evaluates the potential clinical benefit of trilaciclib in preventing chemotherapy-induced myelosuppression in patients receiving chemotherapy. | NCT04504513 | |
| proliferating cells + PD-L1 | carboplatin + etoposite | Atezolizumab | SCLC. This trial investigates the potential clinical benefit of trilaciclib in preserving the bone marrow and the immune system, and enhancing antitumor efficacy when administered with chemotherapy. | NCT03041311 | |
| proliferating cells | topotecan | SCLC. This trial investigates the potential clinical benefit of trilaciclib in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to chemotherapy. | NCT02514447 | ||
| proliferating cells | carboplatin + gemcitabine | metastatic TNBC. This study investigates the potential clinical benefit of trilaciclib in preserving the bone marrow and the immune system, and enhancing chemotherapy antitumor efficacy when administered prior to chemotherapy. |
NCT02978716 | ||
| Lerociclib | ER | ER antagonist: fulvestrant | HR+/HER2-metastatic breast cancer | NCT02983071 | |
| EGFR | osimertinib | EGFR mutant NSCLC | NCT03455829 | ||
| SHR6390 | ER | ER antagonist: fulvestrant | HR+/HER2-recurrent/metastatic breast cancer | NCT03481998 | |
| aromatase | letrozole, anastrozole | HR+/HER2-recurrent/metastatic breast cancer |
NCT03966898; NCT03772353 |
||
| EGFR/HER2 | pyrotinib | HER2+ gastric cancer, HER2+ metastatic breast cancer |
NCT04095390; NCT03993964 |
||
| AR | AR-antagonists: SHR3680 | metastatic TNBC | NCT03805399 | ||
| PF-06873600 | endocrine therapy | single agent and then in combination with endocrine therapy | HR+/HER2-metastatic breast cancer, ovarian and fallopian tube cancer, TNBC and other tumors | NCT03519178 | |
| FCN-473c | aromatase | Letrozole | ER+/HER2-advanced breast cancer | NCT04488107 |