ABSTRACT
Objective: This study investigated the relationship between therapeutic techniques and session impact, by examining the replicability of findings observed in a university-based training clinic (Boswell et al., 2010) in another practice-oriented setting: private practice.Method: N = 8 therapists completed session-level assessments of their technique use for N = 38 clients. The same client sample completed session-level assessments of session outcome. Technique-outcome associations were examined with multilevel models.Results: As in Boswell et al., common factors were associated with positive session impact. For clients who received higher average common factor techniques (relative to their own therapist's caseload), session impact was the poorest in sessions with higher behavioral change techniques use (relative to the client's own average). Moreover, clients with the lowest average common factor techniques (relative to their therapist's caseload) reported better session impact in sessions that involved a higher degree of session-level behavioral change techniques (relative to their own average).Conclusion: In line with Boswell et al., therapists should be mindful of the consistency of their routine technique use between- and within-clients, and this can be aided through collection of their own practice-oriented data.
ABSTRACT
Multiple tumor types overexpress Nectin-4 and the antibody-drug conjugate (ADC), enfortumab vedotin (EV) shows striking efficacy in clinical trials for metastatic urothelial cancer, which expresses high levels of Nectin-4, validating Nectin-4 as a clinical target for toxin delivery in this indication. Despite excellent data in urothelial cancer, little efficacy data are reported for EV in other Nectin-4 expressing tumors and EV therapy can produce significant toxicities in many patients, frequently leading to discontinuation of treatment. Thus, additional approaches to this target with the potential to extend utility and reduce toxicity are warranted. We describe the preclinical development of BT8009, a "Bicycle Toxin Conjugate" (BTC) consisting of a Nectin-4-binding bicyclic peptide, a cleavable linker system and the cell penetrant toxin mono-methylauristatin E (MMAE). BT8009 shows significant antitumor activity in preclinical tumor models, across a variety of cancer indications and is well tolerated in preclinical safety studies. In several models, it shows superior or equivalent antitumor activity to an EV analog. As a small hydrophilic peptide-based drug BT8009 rapidly diffuses from the systemic circulation, through tissues to penetrate the tumor and target tumor cells. It is renally eliminated from the circulation, with a half-life of 1-2 hours in rat and non-human primate. These physical and PK characteristics differentiate BT8009 from ADCs and may provide benefit in terms of tumor penetration and reduced systemic exposure. BT8009 is currently in a Phase 1/2 multicenter clinical trial across the US, Canada, and Europe, enrolling patients with advanced solid tumors associated with Nectin-4 expression.
