Promising combination designs
This table illustrates promising combinational designs that have been proposed for selected therapeutic classes and how often these designs are presented in our database. The design pattern column shows a key pattern for a combination, which can also contain additional agents. The number of detected arms shows the number of occurrences for each design pattern among clinical trials. Note, our analysis did not take into account administration schedules and doses. The number for unique designs is written in parentheses. The number of clinical trials column shows the number of clinical trials (by NCTID) for each combination design. The phase structure column and the rational column show the phase counts for each combination design and biologic rationale to use this design respectively. Data are to February 2020.
| Design Pattern | Number of Detected Arms | Number of Clinical Trials | Phase Structure | Possible Rationale | Reference for Rationale |
|---|---|---|---|---|---|
| Alkylating agents + TTF | 12 (7 unique) | 12 | I – 9 trials II – 3 trials | • Lack of overlapping resistance mechanisms • Inhibition of DSB-repair mechanism to increase toxicity | (Branter et al., 2018) |
| Angiogenesis inhibitors + TTF | 6 (3 unique) | 6 | I – 1 trial II – 5 trials | • Reduced toxicity of angiogenesis inhibitors | (Branter et al., 2018) |
| Spindle poisons + TTF | Untested | Untested | NA | • Synergetic disruption of spindle functioning | (Branter et al., 2018) |
| Immune therapy + TTF | 4 (4 unique) | 4 | I – 1 trial II – 3 trials | • No hindrance on immune response • Improving infiltration of immune effector cells | (Branter et al., 2018) |
| Immune checkpoint inhibitors + DC vaccination | 4 (4 unique) | 4 | I – 2 trials II – 2 trials | • Increased immune response toward neoantigens | (Garg et al., 2017; Sabado et al., 2017) |
| Immune checkpoint inhibitors + antibody-drug conjugates | Untested | Untested | NA | • Antibody-drug conjugates (their warheads) can induce immunogenic cell death that could be augmented with checkpoint inhibitors • Combination demonstrates promising results in several tumor types | (Beck et al., 2017) |
| Immune checkpoint inhibitors + vaccine (any) | 19 (19 unique) | 19 | I – 11 trials II – 6 trials | • Improved response rates | (Barbari et al., 2020) |
| Immune checkpoint inhibitors + radiation therapy | 36 (26 unique) | 31 | I – 19 trials II – 10 trials III – 2 trials | • Improved response rates • May overcome resistance • Antigen release • Favorable immune-activating environment | (Barbari et al., 2020) |
| Immune checkpoint inhibitors + chemotherapy | 27 (21 unique) | 21 | I – 12 trials II – 9 trials III – 1 trials | • Improved response rates • Antigen release • Favorable immune-activating environment | (Barbari et al., 2020) |
| Immune checkpoint inhibitors + modified effector cells | 4 (4 unique) | 3 | I – 2 trials II – 1 trial | • Increased persistence of CAR T cells • Increased antitumor activity | (Barbari et al., 2020; Grosser et al., 2019; Jackson et al., 2016) |
| CAR T cells + oncolytic viruses | Untested | Untested | NA | • Increased persistence of CAR T cells • Favorable proinflammatory environment for both CARs and oncolytic viruses | (Ajina and Maher, 2019; Guedan and Alemany, 2018; Tang et al., 2020; Twumasi-Boateng et al., 2018) |
| Kinase inhibitor + kinase inhibitor | 24 (17 unique) | 22 | I – 13 trials II – 7 trials IV – 2 trials | • Tackling with tumor heterogeneity • Targeting pathway network to overcome drug resistance | (Yap et al., 2013) |
| Angiogenesis inhibitors + immune therapy | 28 (26 unique; almost all antiangiogenic agents are represented by bevacizumab) | 26 | I – 12 trials II – 14 trials | • Reduced hypoxia should be favorable for immune response | (Ramjiawan et al., 2017) |
DSB, DNA double-strand breaks; NA, not available.