Tumor reduction and ctDNA/cfDNA dynamics at D15 and at SRG revealed differential tumor biological behavior
| Patient ID | Tumor decreased D15 | Tumor decreased pre-surgery | ctDNA detectable PRE | ∆ctDNAd15 | ∆ctDNASRG (%) | ∆cfDNAd15 (fold change) | Group classification* |
| S-001 | Yes | Yes | No | – | – | ×1.2 | N/A |
| S-002 | Yes | Ø | Yes | −71% | −100 (cleared) | ×9 | 1A |
| S-004 | Yes | Yes | Yes | −81% | −87 | ×4 | 1A |
| S-006 | No | Yes | Yes | −29% | −71 | ×1.5 | 1B |
| S-007 | Yes | Yes | Yes | −96% | −99 | ×3.5 | 1A |
| S-008 | Yes | No | No | – | – | ×7 | 1A |
| S-009 | Ø | No (increased) | No | – | Detectable (+100) | ×4 | PD† |
| S-010 | Yes | Yes | Yes | −62% | −77 | ×3.7 | 1A |
| S-011 | No | Ø | Yes | +100% | −100 (cleared) | ×2.5 | 1B |
| S-013 | Ø | Ø | Yes | −100% (cleared) | Undetectable | ×6.4 | 1A |
*Cohort groups according to tumor biological behavior: Patients were classified into Group 1A if had at least two of the following criteria after treatment with sitravatinib alone and before nivolumab dosing (D15) = (1) ∆ctDNAd15>(−50%); (2) ∆cfDNAd15>3.8 fold change; (3) Tumor decrease at D15. Patients were classified into Group 1B if criteria 1 and 3 were not met at day 15 but were met pre-surgery (after nivolumab dosing). Patients S-001 and S-009 were excluded as they were not fitting any of these criteria.
†Patient S-009 was considered PD as per the criteria defined above (patient had tumor regrowth and spike in ctDNA before surgery) although patient had responded while on sitravatinib and had clinical to pathology downstaging from T4aN1 to pT3pN0.
Ø, not assessable; cfDNA, cell-free DNA; ctDNA, circulating tumor DNA; D15, day 15; ID, identification; N/A, not applicable; PD, patient with progressive disease; PRE, pretreatment; SRG, pre-surgery.