*2.2.3.2 Methods*

*Advances in Precision Medicine Oncology*

metastatic cancer.

*2.2.2.2 Methods*

treatment.

combining ICIs with antiangiogenesis therapy could have the synergistic antitumor effects needed to enhance the efficacy of the individual therapies [37]. This phase 1 single-center clinical trial beginning in 2018 evaluated the safety and tolerability of TKI, apatinib, and PD-1 inhibitor, nivolumab, in patients with unresectable or

All subjects enrolled had cancer that was refractory to prior lines of treatment. Specifically, patients were required to already be at least three cycles into nivolumab treatment and must be planning to continue this treatment throughout the trial period. Thirty patients in total were enrolled, ten of which were in part 1 of this study, where they were treated with apatinib using a classic 3 + 3 dose escalation method in order to determine the maximum tolerated dose. Part 2 of this study included twenty subjects and was an expansion phase using the MTD. The percent of change in tumor responses and amount of time until progression were measured

*2.2.2.3 Preliminary results presented at the Connective Tissue Oncology Society* 

The overall response rate reported was 13.3% (95% CI: 3.8% to 30.7%) and the median PFS was 7.2 months (95% CI: 5.3 to 9.0 months). No complete responses occurred although four patients achieved a partial response and the majority of patients achieved stable disease. Seven patients from part 1 and six patients from part 2 experienced ≥ grade 3 treatment emergent adverse events including fatigue (10.0%), hypertension (10.0%), nausea (10.0%), anemia (16.7%) and asthenia (10.0%). Two patients experienced fatal adverse events, although there were no noted treatment related deaths. Nine patients eventually discontinued the study due to toxicity, and nine patients also received a dose reduction. No unexpected side effects were noted as a result of the combined

The results of this study demonstrate an acceptable safety profile and clinical benefit of combination treatment with nivolumab and apatinib that is worth

*2.2.3 Phase 1, Open-Label, Safety Study of Escalating Doses of Ex Vivo Expanded, Autologous Natural Killer Cells in Patients With Pathologically Confirmed Cancer Refractory to Conventional Therapy (NCT03941262). Sant P.* 

Natural killer (NK) cells are the cytotoxic lymphocytes of the innate immune system [38]. As a rapid, first line of defense, NK cells are able to lyse tumor cells independent of the expression of tumor-associated antigens and/or the presence of major histocompatibility complex class I (MHC-I) molecules. This ability is crucial as cancer cells have been shown to downregulate the expression of MHC-I on their cell surface as a way to evade detection by immunosurveillance mechanisms [39].

and analyzed using RECIST v1.1 and iRECIST criteria.

*meetings, November, 2020*

*2.2.2.4 Conclusions/future directions*

exploring further in additional clinical studies.

*Chawla, Principal Investigator*

*2.2.3.1 Background & rationale*

**12**

This study is a nonrandomized, multicenter safety study of adoptively infused, ex vivo expanded autologous NK cells to treat male and female adult patients with advanced or metastatic, intractable cancer. Study subjects were placed in one of three cohorts and received SNK01 in an open-label fashion according to a 3 + 3 Phase 1 dose-escalation method. Patients received 5 weekly infusions for a period of 5 weeks, and restaging imaging was performed on week 6. The primary objective of this study was a safety assessment based on the incidence and severity of dose-limiting toxicities and other adverse events observed by evaluating vital signs, clinical laboratory findings and physical examination abnormalities. The adverse events were graded according to the CTCAE v5.0 criteria. Subjects' performance status was assessed and recorded using ECOG criteria. The secondary objective is to evaluate the efficacy of the treatment by measuring the objective response rate of target lesions observed via CT scan using iRECIST criteria.
