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PROOF 302 is an ongoing randomized, double-blind, placebo-controlled, adjuvant phase III trial (NCT04197986) in approximately 218 patients from 120 centers worldwide. Eligibility criteria include post-surgical high-risk muscle-invasive upper tract urothelial cancer (85% of patients) or urothelial bladder cancer (15%), susceptible FGFR3 alterations (activating mutations, gene fusions or rearrangements), ≤120 days following radical surgery and ineligible for/or refusing cisplatin-based (neo)adjuvant chemotherapy. Patients receive either oral infigratinib 125 mg or placebo daily on days 1–21 of a 28-day cycle for up to 52 weeks or until recurrence, unacceptable toxicity or death. Primary end point: centrally determined disease-free survival (DFS); secondary end points: investigator-assessed DFS, metastasis-free survival, overall survival and safety/tolerability; exploratory end points: correlative biomarker analysis, quality-of-life and infigratinib pharmacokinetics.

11057 Background: Historically, Diversity, Equity, and Inclusion (DEI) efforts have largely been left out of private practice medical facilities – mainly present in large academic hospital centers. Virginia Oncology Associates (VOA), a member of The US Oncology Network, is an independent community oncology and hematology practice specializing in the diagnosis and treatment of cancer and blood disorders. VOA has approximately 600 total employees consisting of physicians and clinical and non-clinical staff. In August of 2020, VOA launched an initiative to foster a culture of inclusion with the creation of its Inclusion Council (IC). Sixteen employees’, both clinical (3 physicians) and non-clinical, were chosen to participate. The council reports to VOA’s joint policy board. Methods: The council partnered with an outside organization, Virginia’s Center for Inclusive Communities, to launch a practice-wide DEI training program focusing on unconscious bias and microaggression. The training was initially planned to be in person, but due to the constraints of the COVID pandemic, the training was performed using a virtual platform. The members of IC attended three two-hour sessions while other staff members and physicians were mandated to participate in at least one training session. After completion of the sessions, a survey was sent to all employees and physicians to measure the impact of DEI training. All employees were also given the opportunity to provide additional, anonymous, written feedback. Results: Table. A total of 169 employees responded. 72% of respondents agreed or strongly agreed that the program increased awareness of unconscious bias and microaggression, 67% felt that the program helps foster a culture of inclusion in the workplace, and 66% of respondents felt that the program met expectations. Conclusions: DEI efforts are vital in all aspects of health care delivery and oncology settings. DEI training met staff expectations and positively fostered a culture of inclusion by bringing attention to unconscious bias and microaggression in a community oncology practice.[Table: see text]

TPS600 Background: Radical surgery ± cisplatin‐based (neo)adjuvant therapy (NAT) is the mainstay of treatment for invasive urothelial carcinoma of the upper urinary tract (UTUC) or bladder (UBC), but recurrence rates are high. Furthermore, many patients (pts) are unable to receive NAT because of cisplatin ineligibility. Fibroblast growth factor receptor 3 (FGFR3) genetic alterations occur in up to 70% of UTUC and up to 20% of UBC, and may constitute a potential candidate for targeted therapy. Infigratinib (BGJ398), a selective FGFR1–3 inhibitor, has shown promising clinical activity and tolerability in pts with advanced urothelial carcinoma having FGFR3 alterations [Pal et al. Cancer Discov 2018]. PROOF 302 has been designed to investigate the efficacy and safety of infigratinib versus placebo as adjuvant therapy in pts with high-risk invasive urothelial carcinoma and FGFR3 alterations. Methods: PROOF 302 is a randomized, double-blind, placebo-controlled, phase III study of approx. 218 pts. Adults with high-risk invasive UTUC or UBC with FGFR3 genetic alterations (i.e. mutations, gene fusions or translocations) who are ≤120 days following surgical resection and ineligible for cisplatin-based adjuvant chemotherapy or with residual disease after cisplatin- based NAT are eligible. Those who received non cisplatin-based NAT are eligible if they have residual disease and are ineligible for adjuvant cisplatin. Pts receive oral infigratinib 125 mg or placebo (1:1 ratio) once daily on days 1–21 every 28 days for up to 52 weeks or until disease recurrence, unacceptable toxicity or death. Primary endpoint: centrally reviewed disease-free survival (DFS). Secondary endpoints: DFS including intraluminal low-risk recurrence; metastasis-free survival; overall survival; DFS (per investigator); safety and tolerability. Exploratory endpoints include: quality of life; pharmacokinetics; cell-free DNA (cfDNA) and/or RNA for resistance mechanisms. The study will involve approximately 120 centers worldwide. Enrollment is expected to begin in January 2020. Trial registration: EudraCT 2019-003248-63. Clinical trial information: EudraCT 2019-003248-63.

TPS335 Background: EZH2 is frequently mutated and/or overexpressed in numerous cancers. High EZH2 expression is correlated with poor outcomes in prostate cancer patients (Varambally, 2002). EZH2 inhibition combines synergistically with anti-androgen therapies in preclinical models of advanced prostate cancer, suggesting epigenetic reprogramming as a pathophysiologic mechanism to enhance the combination therapy (Ku, 2017; Xiao 2018; Constellation, unpublished). CPI-1205 is a potent, selective, and cofactor-competitive inhibitor of wild type and mutant EZH2 catalytic activity, which demonstrates anti-proliferative effects in prostate and other cancer cell models. Methods: We present a Phase 1b/2 multicenter study of CPI-1205 combined with either E or A/P in patients with mCRPC, which includes phase 1 dose escalation, an expansion cohort in heavily pretreated patients (HPEC), and a randomized phase 2 study. Key eligibility criteria include progressive mCRPC in patients previously treated with a second-generation androgen inhibitor, ECOG 0-1, and measurable or non-measurable disease. During the phase 1b, patients will receive CPI-1205 continuously in 28-day cycles combined with the standard dose of either E (160mg PO once daily) or A/P (1000mg PO once daily/5 mg BID). The primary objective in Phase 1b is to determine the safety, tolerability, and recommended phase 2 dose (RP2D) of CPI-1205 combined with either E or A/P. Secondary objectives include safety, pharmacokinetic and pharmacodynamic profiles, and anti-tumor activity. The HPEC arm, with Simon’s 2-stage design, may begin with the regimen that is deemed safe by the study safety committee. The primary endpoint of the HPEC arm is objective response rate (ORR) per PCWG3, with a requirement ≥ 1 measurable lymph node at baseline. Once RP2D is established, we will start a randomized Phase 2 trial of E or A/P combined with CPI-1205 vs. E or A/P alone. The co-primary endpoint includes PSA50 and composite response rate (either CTC 30% reduction or ORR per PCWG3). Patient accrual in US sites began in December 2017. Clinical trial information: NCT03480646.

Meeting abstracts Metastatic bladder cancer (MBC) is a relatively chemosensitive neoplasm yet response durations are generally short-lived. Recently, immune checkpoint blockade has demonstrated unparalleled activity in heavily pre-treated patients (pts) with MBC. The role of standard chemotherapy

79 Background: Following docetaxel (D), treatment options for mCRPC include cabazitaxel (CBZ), abiraterone acetate (AA), and enzalutamide. With the introduction of new agents, optimal sequencing is undefined. We evaluated the prevalence of sequencing of AA and CBZ following D in a large community-based cohort to develop a hypothesis for the most optimal sequence. Methods: A retrospective analysis of treatment patterns using the MSH iKnowMed EHR was conducted. Post-D mCRPC patients receiving CBZ and/or AA at full EHR sites with ≥2 visits were included; clinical trial patients excluded. CBZ utilization between Jun’10 and May’12 and sequencing of CBZ or/and AA from Apr’11 and May’12 (when both drugs were available) were examined. OS, time to treatment failure (TTF), and demographics analyses are ongoing. Results: 667 evaluable patients were identified. Overall CBZ (n=359 pts/2 y) utilization declined between Jun’10-May’11 (n=232) and Jun’11-May’12 (n=127). From Apr’11 to May’12: overall AA (n=465 pts/y) utilization increased between Mar-May’11 (n=73) to Jun-Aug’11 (n=164) and subsequently decreased (n=57) from Mar-May’12. Between Apr’11-May’12, 130 patients received both CBZ and AA. More men (P

5018 Background: The abundant expression of prostate specific membrane antigen (PSMA) on prostate cancer cells provides a rationale for antibody therapy. PSMA ADC is a fully human antibody to PSMA linked to the microtubule disrupting agent monomethyl auristatin E (MMAE). It binds PSMA and is internalized within the cancer cell where cleavage by lysosomal enzymes release free MMAE, causing cell cycle arrest and apoptosis. A phase 1 dose escalation study of PSMA ADC in taxane-refractory mCRPC has been completed. Methods: Patients with progressive mCRPC following taxane-containing chemotherapy and ECOG status of 0 or 1 were eligible. PSMA ADC was administered by IV infusion Q3W for up to 4 cycles. Safety, pharmacokinetics, PSA, circulating tumor cells (CTC), immunogenicity and clinical progression were assessed. Serum PSMA ADC and total anti-PSMA ADC antibodies were measured by ELISA, and free MMAE was measured by LC/MS/MS.The dosing cohorts ranged from 0.4 mg/kg to 2.8 mg/kg. Subjects who benefitted from PSMA ADC were eligible for treatment in an extension study. Results: 52 subjects were dosed in 9 dose levels. All subjects received prior docetaxel, 6 also received cabazitaxel and 3 subjects also received paclitaxel. PSMA ADC was generally well tolerated with the most commonly seen adverse events being anorexia and fatigue. 16 patients reported peripheral neuropathies, including 3 with grade 3. Dose limiting toxicities (DLT) seen at 2.8 mg/kg were neutropenia (one death) and reversible elevations in liver function tests (LFTs). Antitumor activity was manifested as reductions either in PSA or in CTCs in approximately 50% of patients at ≥ 1.8 mg/kg PSMA ADC. Exposure to PSMA ADC increased with dose and was ~1,000-fold greater than MMAE exposure. There was no accumulation. Conclusion: PSMA ADC in this study was generally well tolerated in subjects with progressive mCRPC, previously treated with taxane. Antitumor activity was seen at doses ≥ 1.8 mg/kg. DLTs were neutropenia and reversible LFT abnormalities. The maximum tolerated dose was determined to be 2.5 mg/kg. A phase 2 trial of PSMA ADC in taxane refractory mCRPC has been initiated at 2.5 mg/kg. Clinical trial information: NCT01414283.

e15040 Background: A previously reported phase II trial demonstrated that the addition of C, a chimeric monoclonal antibody that binds EGFR to MP for mCRPC following docetaxel did not extend overal...

4555 Background: Cetuximab (C), a chimeric monoclonal antibody with binding affinity to the epidermal growth factor receptor (EGFR), is active against androgen-independent prostate cell (AIPC) lines. No established therapy prolongs survival in CRPC patients (pts) who have received prior docetaxel (D). Mitoxantrone (M) is often used in this setting. In other cancers, C can restore sensitivity to chemotherapy. The combination of C+M was tested in D-treated CRPC pts. Methods: Pts with metastatic CRPC with evidence of progression (PSA or imaging) after D were eligible. PCWG2 guidelines for nonmeasurable disease applied. Treatment: Arm 1 (CM) C 250 mg/m2 (except 400 mg/m2 on Day 1 Cycle 1) Days 1, 8, & 15 and M 12 mg/m2 Day1; Arm 2 (M) 12 mg/m2 Day1; all pts took oral prednisone (P) 10 mg daily. Cycles were 21-days. Arm 2 pts could crossover to Arm 1 if progression was documented prior to Cycle 7 and were analyzed as Arm 2b. Radiological assessments of disease and PSA were done every 4 cycles. Results: 115 pts...