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Purpose:Rocapuldencel-T is an autologous immunotherapy prepared from mature monocyte-derived dendritic cells (DC), coelectroporated with amplified tumor RNA plus CD40L RNA. This pivotal phase III trial was initiated to investigate the safety and efficacy of a combination therapy dosing regimen of Rocapuldencel-T plus sunitinib in patients with metastatic renal cell carcinoma (mRCC).Patients and Methods:Patients received either Rocapuldencel-T plus standard of care (SOC) or SOC treatment alone. The primary objective compared overall survival (OS) between groups. Secondary objectives included safety assessments, progression-free survival (PFS), and tumor responses based on RECIST 1.1 criteria. Exploratory analyses included immunologic assessments and correlates with OS.Results:Between 2013 and 2016, 462 patients were randomized 2:1, 307 to the combination group and 155 to the SOC group. Median OS in the combination group was 27.7 months [95% confidence interval (CI) 23.0–35.9] and 32.4 months (95% CI, 22.5–) in the SOC group HR of 1.10 (95% CI, 0.83–1.40). PFS was 6.0 months and 7.83 months for the combination and SOC groups, respectively [HR = 1.15 (95% CI, 0.92–1.44)]. The ORR was 42.7% (95% CI, 37.1–48.4) for the combination group and 39.4% (95% CI, 31.6–47.5) for the SOC group. Median follow up was 29 months (0.4–47.7 months). On the basis of the lack of clinical efficacy, the ADAPT trial was terminated on February 17, 2017. Immune responses were detected in 70% of patients treated with Rocapuldencel-T, and the magnitude of the immune response positively correlated with OS. In addition, we report the survival-predictive value of measuring IL-12 produced by the DC vaccine and the observation that high baseline numbers of T regulatory cells are associated with improved outcomes in DC-treated patients, but are associated with poor outcomes in patients receiving SOC treatment. No serious adverse events attributed to the study medication have been reported to date.Conclusions:Rocapuldencel-T did not improve OS in patients treated with combination therapy, although the induced immune response correlated with OS. Moreover, we identified two potential survival-predictive biomarkers for patients receiving DC based immunotherapy, IL-12 produced by the DC vaccine and higher numbers of T regulatory cells present in the peripheral blood of patients with advanced RCC.

subsequent standard of care treaments

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ADAPT study group and participating centers

Introduction: Biomarker testing identifies actionable mutations to inform targeted tx for personalized healthcare. This study examined biomarker testing and tx patterns ≤ 90 days (d) after advanced (adv) or metastatic (met) diagnosis (Dx) at the OneOncology (OneOnc) network. Methods: A retrospective observational study using the nationwide Flatiron Health electronic health record-derived de-identified database from selected OneOnc practices included patients (pts) ≥ 18 y, who had Dx between 1/1/18 - 4/30/21 with adv non-small cell lung cancer (aNSCLC), met breast cancer (mBC), met colorectal cancer (mCRC) or adv melanoma (aMel), with ≥ 1 visit ≤ 90 d after adv or met Dx, and who had ≥ 90 d follow-up. Descriptive analyses were conducted. Results: Of the pts who met the inclusion criteria, 91% of 2,391 aNSCLC, 100% of 1,043 mBC, 92% of 1,344 mCRC and 84% of 358 aMel had ≥ 1 biomarker test at any time, where 78% aNSCLC, 82% mBC, 70% mCRC and 67% aMel were tested ≤ 90 d after adv or met Dx. Testing rates varied by biomarker (Table). Across indications, ≥ 70% commercial health insured vs. ≥ 50% Medicaid insured pts were tested. Commercial labs were used in 91% aNSCLC, 86% mBC, 80% mCRC and 93% aMel. Amongst treated pts, 14% of 1,693 aNSCLC, 2% of 725 mBC, 22% of 881 mCRC and 25% of 169 aMel received tx before test results were available. NGS was tested in 69% aNSCLC, 29% mBC, 70% mCRC, and 57% aMel. The median turnaround time (TAT) from adv or met Dx to 1st test result from NGS vs other biomarker tests was 26 vs 13 d in aNSCLC, 14 vs 5 d in mBC, 35 vs 10 d in mCRC and 44 vs 21 d in aMel. Conclusions: The majority of testing occurred ≤ 90 d after adv or met Dx, while 18% - 33% of pts were not tested. The varying testing rates across indications reflect the intended use of biomarker tests to guide 1st line therapies. More than 75% pts treated after testing result available signal community oncologist recognizing the importance of biomarker testing in guiding tx decisions. Improvements in TAT for NGS may reduce the issue of tx decisions made prior to test results. Table. Biomarker testing rate by indication amongst pts tested ≤ 90 d after adv or met Dx aNSCLCn=1,858 mBCn=859 mCRCn=936 aMeln=239 EGFR 89% ALK 87% BRAF 81% 80% 98% KRAS 67% 82% ROS1 86% PD-L1 85% 18% 27% ER 93% PR 93% HER2 92% BRCA 20% PIK3CA 28% MMR/MSI 93% NRAS 77% 49% KIT 50% ER, estrogen receptor; MMR, mismatch repair; MSI, microsatellite instability; PR, progesterone receptor. Citation Format: Esprit Ma, Elaine Yu, Tania Szado, Richard Price, Craig S. Meyer, Anuj Shah, Baiyu Yang, Daniel Vaena, Davey Daniel, Dennis Slater, Harry Staszewski, Bruno Fang, Lasika Seneviratne, Lee Schwartzberg. Biomarker testing and treatment (tx) patterns in a large community oncology network [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2267.

In the precision medicine era, molecular testing in advanced cancer is foundational to patient management. Molecular tumor boards (MTBs) can be effective in processing comprehensive genomic profiling (CGP) results and providing expert recommendations. We assessed an MTB and its role in a community setting. This retrospective analysis included patients with MTB recommendations at a community-based oncology practice January 2015 to December 2018, exclusions were death within 60 days of the MTB and/or no metastatic disease. Potentially actionable genomic alterations from CGP (immunohistochemistry, in-situ hybridization, next-generation sequencing) were reviewed bi-weekly by MTB practice experts, pathologists, genetic counselors, and other support staff, and clinical care recommendations were provided. Subsequent chart reviews determined implementation rates of recommendations. In 613 patients, the most common cancers were lung (23%), breast (19%), and colorectal (17%), others included ovarian, endometrial, bladder, and melanoma. Patients received 837 actionable recommendations: standard therapy (37%), clinical trial (31%), germline testing and genetic counseling (17%), off-label therapy (10%), subspecialty multidisciplinary tumor board review (2%), and advice for classifying tumor of unknown origin (2%). Of these recommendations, 36% to 78% were followed by the treating physician. For clinical trial recommendations (n = 262), 13% of patients enrolled in a clinical trial. The median time between CPG result availability and MTB presentation was 12 days. A community oncology-based comprehensive and high-throughput MTB provided useful clinical guidance in various treatment domains within an acceptable timeframe for patients with cancer in a large community setting.

Chromophobe renal cell carcinoma (chRCC) is the third most common type of RCC with distinct biology compared to other kidney cancer subtypes. The heterogeneity between the RCC subtypes is associated with noticeable differences in tumor aggressiveness and risk for the development of metastatic disease. ChRCC is characterized by chromosomal aneuploidy, TP53, PTEN, and mitochondrial gene mutations. Though the therapeutic landscape of clear cell RCC (ccRCC) has significantly evolved over the past decade, limited progress has been seen in chRCC due to its infrequent incidence. In fact, the therapeutic approach for chRCC is often extrapolated from ccRCC treatments or studies that combine several forms of nccRCC subtypes. In the new era of genetic profiling of tumors and targeted therapeutics, this review describes the epidemiology, pathology, molecular characteristics, and current management with ongoing clinical trials for chRCC.

Preclinical studies demonstrated the ability of an adenovirus/PSA (Ad/PSA) vaccine to induce strong anti-PSA immune responses, and these responses were capable of destroying prostate-specific antigen (PSA)-secreting mouse prostate tumors. A series of preclinical studies have demonstrated the superiority of the Ad/PSA vaccine to other PSA vaccines for the induction of anti-PSA immune responses, the ability of Ad/PSA vaccination combined with cytokine gene therapy and the TLR9 agonist CpG to enhance the anti-prostate tumor immunotherapy, and the reduction of negative regulatory elements when the vaccine was combined with 5-fluoruracil administration. A phase I clinical trial of the Ad/PSA vaccine in men with metastatic castrate-resistant prostate cancer demonstrated the safety of the vaccine even at the highest single dose permitted by the FDA. Currently, a phase II trial of the Ad/PSA vaccine is underway treating patients in two protocols. Thus far 81 patients have been enrolled and vaccinated. Early results from the patients evaluated to date demonstrated the induction of anti-PSA T cell responses, and the majority of patients evaluated at this time had demonstrated an increase in PSA doubling times.