Specific communication practices of multiple professionals in health care settings can impact patient outcomes. This study, conducted at a large Children's Hospital, sought to determine the extent to which patient-centered communication (PCC) affected satisfaction with communication and with care itself. Parents of child patients (N = 195) reported on the communication practices of physicians, nurses, and hospital staff members during their most recent stay in the hospital. Surveys were completed on site. Health care providers' use of PCC behaviors, especially immediacy and perceived listening, was positively associated with satisfaction with care and with communication. In addition, PCC behaviors were perceived to be used more frequently with children in better health than with children with poorer health status.

Background: Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2+ solid tumors, significant unmet medical needs still exist, especially in tumors other than breast and gastric. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor redirects T cells to tumor cells, and upon tumor cell recognition, co-opts the natural T cell receptor (TCR) to yield safer anti-tumor responses versus chimeric antigen receptor (CAR) T cells. In preclinical studies, TAC T cells led to complete tumor clearance in mouse models of human cancer, without any TAC-related toxicities. In the ongoing clinical trial (NCT04727151), TAC01-HER2 treatment of HER2+ solid tumors is hypothesized to result in safe and effective anti-tumor responses. Subjects undergo leukapheresis, bridging therapy (if needed) while their TAC01-HER2 are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion. Trial Design and Early Results: In phase I dose escalation, the primary objective is to evaluate the safety of TAC01-HER2 at increasing doses of 0.3, 0.8, 3, and 8 × 106 cells/kg in HER2+ solid tumors (1+, 2+ or 3+ as identified by immunohistochemistry) in adult subjects who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are assessed up to 28 days from cell infusion. In Phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other solid tumor types. As of 12 Dec 2022, 12 patients have been treated in Cohorts 1-4 with breast, colorectal, gall bladder, gastro-esophageal junction, gastric and ovarian tumors. No DLTs or neurotoxicity events have been reported. All patients treated so far at Cohorts 3 and 4 (3 × 106 and 8 × 106 cells/kg, respectively) experienced Grade ≤2 CRS which were resolved with standard of care treatments. Eight subjects have reported a total of 15 serious adverse events, all unrelated to TAC01-HER2 except for a Grade 1 and a Grade 2 CRS, both resolved with standard of care. Most adverse events were related to LDC or the underlying neoplasm. At Cohort 2, a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) at 1st scan, with a 36.5% reduction in measurable disease and clinical benefit was maintained for 6 months. A 71% disease control rate was observed at Cohorts 2 and 3 at 1st scan (0.8 × 106 and 3 × 106 cells/kg, respectively)). Dose escalation of TAC01-HER2 is ongoing, with the first subject treated at Cohort 4. These results in a heavily pre-treated cancer population show manageable safety and promising clinical activity with a novel T cell therapy that may have broad clinical applicability in HER+ cancers. Citation Format: Ecaterina Elena Dumbrava, Daniel Olson, Samuel Saibil, Brooke Pieke, Mridula A. George, Riemke Bouvier, Miriam Gavriliuc, Kelly Gruber, Kara Moss, Nathan Ternus, Maria Apostolopoulou, Deyaa Adib, Benjamin L. Schlechter. A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr CT234.

TPS816 Background: HER2 overexpression is well established as a therapeutic target in breast cancer and can be seen in a variety of gastrointestinal malignancies, notably in gastroesophageal cancer where positivity ranges from 4.4% to 53.4%. The recent approval of HER2-targeted therapies to treat gastroesophageal adenocarcinomas has validated HER2 as an actionable target in these diseases. Recent data also support the emerging role of HER2 directed therapy in colorectal cancer, among other solid tumors. Although patient outcomes have improved, this remains an area of significant unmet medical need. The T cell antigen coupler (TAC) technology is a novel approach to modifying a patient’s own T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor is composed of a HER2-binding domain, similar to a traditional chimeric antigen receptor (CAR) T cell, however unlike CAR T cells, it uses the signaling pathway of the natural T cell receptor (TCR) to avoid off target toxicity. This novel “TAC receptor” is hypothesized to deliver a targeted anti-cancer T cell response with a much-improved safety profile as compared with traditional CAR T cells such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome events (ICANS). In this ongoing clinical trial (NCT04727151), subjects undergo leukapheresis, bridging therapy (if needed) while TAC T cells are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion. Methods: The Phase 1 dose escalation study is underway to investigate the safety and tolerability of TAC01-HER2 in adult subjects with HER2+ solid tumors (1+, 2+ or 3+) who have progressed after ≥2 lines of therapy at dose levels 0.3, 0.8, 3, and 8 x 106 cells/kg. Dose limiting toxicities (DLTs) are assessed up to day 28. A Phase 2 will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in various HER2+ tumors. As of 19 August 2022, 8 subjects have been treated at Dose Levels (DL) 1 and 2, with no observed DLTs, CRS, or ICANS. Five subjects had 11 serious adverse events, all unrelated to TAC01-HER2 treatment. A majority of adverse events were related to LDC and/or the underlying disease. At DL 2, a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) on day 29, with a 36.5% reduction in measurable disease. Two additional subjects at DL 2 had stable disease, one with refractory gall bladder cancer (3+ HER2) and one with refractory colorectal cancer (2+ HER2) with no change in tumor measurements compared to baseline. Dose escalation of TAC01-HER2 is ongoing, with the first subject being treated at DL 3. These results in a heavily pre-treated gastrointestinal cancer population show manageable safety and promising efficacy with a novel T cell therapy that may have broad clinical applicability in HER+ cancers. Clinical trial information: NCT04727151 .

2519 Background: Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2+ solid cancers, significant unmet medical needs still exist, especially in tumors other than breast and gastric. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor redirects T cells to tumor cells, and upon tumor cell recognition, co-opts the natural T cell receptor (TCR) to yield safer anti-tumor responses versus chimeric antigen receptor (CAR) T cells. In preclinical studies, TAC T cells led to complete tumor clearance in mouse models of human cancer, without any TAC-related toxicities. Methods: In the ongoing clinical trial (NCT04727151), TAC01-HER2 treatment of HER2+ solid tumors is hypothesized to result in safe and effective anti-tumor responses. Subjects undergo leukapheresis, bridging therapy (if needed) while their TAC01-HER2 are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion. In phase I dose escalation, the primary objective is to evaluate the safety of TAC01-HER2 at increasing doses of 0.3, 0.8, 3, and 8 x 106 cells/kg in HER2+ solid tumors (1+, 2+ or 3+ as identified by immunohistochemistry) in adult subjects who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are assessed up to 28 days from cell infusion. In Phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other solid tumor types. Results: As of 10 Feb 2023, 18 patients have been treated in Cohorts 1-4 with breast, colorectal, gall bladder, gastroesophageal junction, gastric, esophageal, lung, and ovarian cancers. One DLT event of grade 3 pneumonitis has been reported in one subject in Cohort 4 (8 x 106 cells/kg). No neurotoxicity has been reported. Most subjects treated at Cohorts 3 and 4 experienced Grade ≤2 CRS which resolved with standard therapy. Twelve subjects have reported a total of 21 serious adverse events, 17 unrelated to TAC01-HER2 except for one Grade 3 pneumonitis, one Grade 1 and two Grade 2 CRS. Most adverse events were related to LDC or the underlying malignancy. At Cohort 2 (0.8 x 106 cells/kg), a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) at 1st scan, with a 35% reduction in measurable disease and clinical benefit was maintained for 4 months. A 55% disease control rate was observed at Cohorts 2-4 at 1st scan. Conclusions: Dose escalation of TAC01-HER2 is ongoing, with seven subjects treated and three more scheduled in Cohort 4. These results in a heavily pre-treated cancer population show manageable safety and promising clinical activity with a novel T cell therapy that may have broad clinical applicability in HER+ cancers. Clinical trial information: NCT04727151 .