Table 1.
Selectively exploiting the cell cycle for cancer
| Holistic cell cycle suppression | Representative clinical trials | Clinical trial number |
|---|---|---|
| CDK4/6 + endocrine therapy | Multiple | Multiple |
| CDK4/6 + MEK inhibition | Study of the CDK4/6 inhibitor palbociclib (PD-0332991) in combination with the MEK inhibitor binimetinib (MEK162) for patients with advanced KRAS mutant non-small-cell lung cancer | NCT03170206 |
| Palbociclib and binimetinib in advanced triple-negative breast cancer (PALBOBIN) | NCT04494958 | |
| Binimetinib and palbociclib or TAS-102 in treating patients With KRAS and NRAS mutant metastatic or unresectable colorectal cancer | NCT03981614 | |
| CDK4/6 + KRAS (G12C)inhibition | Adagrasib in combination with palbociclib in patients with advanced solid tumors (KRYSTAL-16) | NCT05178888 |
| Sotorasib activity in subjects with advanced solid tumors with KRAS p. G12C mutation (CodeBreak 101) | NCT04185883 | |
| CDK4/6 + ERK inhibition | A basket trial of an ERK1/2 inhibitor (LY3214996) in combination with abemaciclib | NCT04534283 |
| CDK4/6 + PI3K inhibition | Testing the addition of copanlisib to usual treatment (fulvestrant and abemaciclib) in metastatic breast cancer | NCT03939897 |
| A study evaluating the efficacy and safety of inavolisib + palbociclib + fulvestrant versus placebo + palbociclib + fulvestrant in patients with PIK3CA-mutant, hormone receptor-positive, Her2-negative, locally advanced or metastatic breast cancer | NCT04191499 | |
| CDK4/6 + EGFR inhibition | Osimertinib and abemaciclib in EGFR mutant non-small-cell lung cancer after osimertinib resistance | NCT04545710 |
| CDK4/6/2 inhibition | A safety, pharmacokinetic, pharmacodynamic, and antitumor study of PF-06873600 as a single agent and in combination with endocrine therapy | NCT03519178 |
| Study of NUV-422 in combination with enzalutamide in patients with metastatic castrate-resistant prostate cancer | NCT05191017 | |
| Study of NUV-422 in combination with fulvestrant in patients with HR+HER2−aBC | NCT05191004 | |
| CDK2 inhibition | PF-07104091 as a single agent and in combination therapy | NCT04553133 |
| Collateral vulnerabilities | ||
| CHK1 inhibition | A study of LY2606368 (prexasertib) in patients with solid tumors with replicative stress or homologous repair deficiency | NCT02873975 |
| A study of prexasertib (LY2606368) in participants with extensive stage disease small cell lung cancer | NCT02735980 | |
| WEE1 + PARP inhibition | A study of ZN-c3 and niraparib in subjects with platinum-resistant ovarian cancer | NCT05198804 |
| WEE1 inhibition | Phase II, single-arm study of AZD1775 monotherapy in relapsed small-cell lung cancer patients | NCT02593019 |
| AURK inhibition | Alisertib and pembrolizumab for the treatment of patients with RB-deficient head and neck squamous cell cancer | NCT04555837 |