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5582Background: NKTR-214 is a biased agonist of the IL2Rbg (CD122) pathway that activates and mobilizes CD8 T and NK cells into the tumor microenvironment. The PARP inhibitor rucaparib has demonstr...

35 Background: In men with high grade PC and rapid PSA progression after RP, failure rates are unacceptably high despite salvage RT. Androgen deprivation therapy (ADT) is not curative in this setting and we thus evaluated a novel multi-modality approach of systemic chemotherapy and anti-angiogenic therapy prior to prostate bed salvage RT in a multicenter trial. Methods: Eligible men had a rising PSA of 0.1-3.0 ng/ml within 4 years of RP, no metastatic disease except resected positive nodes, no prior ADT, and Gleason 7-10. Men received 4 cycles of docetaxel 70 mg/m2 q3w with prednisone 5 mg bid and sunitinib 37.5 mg qd for 14/21 days each cycle. Salvage RT (66Gy/33fx) to the prostate bed started at day 100. The primary endpoint was progression-free survival at 2 years (PFS2), defined as a confirmed PSA rise above the post-RT nadir or baseline if no nadir occurred, clinical/radiographic progression, or death from date of enrollment. Safety and dose-limiting toxicities were evaluated. This was a single arm prospective open-label phase 2 trial. Results: Thirty-four men accrued in this multisite Dept. of Defense Prostate Cancer Clinical Trials Consortium trial (median age 62, 85% Caucasian, 9% African American); 24% were node positive at surgery, 47% had Gleason 8-10. Median PSA at entry was 0.54 (range 0.2-2.8) and median time since RP was 11 months. The trial was terminated prematurely due to excess dose-limiting toxicity (9 DLT events) including grade 3 events of hand-foot syndrome (n=4), neutropenic fever (n=2), AST increase (n=1), fatigue (n=1), and vomiting with diarrhea (n=1). PFS at 2 years was 48.9% (95% CI: 32.8%, 67.2%) with a median PFS of 26.2 mo (95% CI: 12.5, -). Six men (17.6%) had an undetectable PSA at 2 years. Conclusions: Sunitinib and docetaxel/prednisone followed by salvage RT resulted in excess pre-specified DLTs. However, efficacy data suggests that some men achieved durable long-term disease control with this aggressive approach. Longer-term follow-up and comparative data with salvage XRT and ADT is needed to fully understand the risks/benefits of this combined modality approach in high risk PSA-recurrent PC. Clinical trial information: NCT00734851.

645 Background: There has been great interest in developing novel agents and strategies to improve chemoradiotherapy (CRT) for locally advanced rectal cancer. Irinotecan, a camptothecin (CPT) analogue, held high potential, but the combination was clinically infeasible due to severe gastrointestinal toxicities. CRLX101, a dynamically tumor targeted nanoparticle-drug conjugate differentially delivers CPT into cancer cells and appears to durably suppress HIF-1α as well as topoisomerase 1, but with less gastrointestinal toxicities than irinotecan. We therefore hypothesized that the addition of CRLX101 to CRT may further improve the therapeutic index in this setting. Methods: CRLX101 was evaluated using murine flank xenograft models (SW480 and HT29) of colorectal cancer alone or in combination with radiotherapy (XRT) and/or 5-FU and compared to CPT plus CRT. Skin toxicity and hematologic toxicity were also studied. In addition, a Phase Ib/II clinical trial (LCCC1315) evaluating the addition of CRLX101 to CRT in the neo-adjuvant treatment of rectal cancer is currently underway. A standard 3 + 3 design was used for the phase Ib with a CRLX101 starting dose of 12 mg/m2 in the first cohort escalating to the CRLX101 monotherapy MTD of 15 mg/m2 in the second. The primary phase 2 end-point is the pathological complete response (pCR) rate from treatment. Results: In the HT29 xenografts model, CRLX101+5FU+XRT delayed tumor growth significantly more than the other treatment regimens evaluated. In the SW480 xenografts model, both CRLX101+5FU+XRT and CRLX101+XRT delayed tumor growth more than other regimens, but there was no statistical advantage to the addition of 5-FU to CRLX101+XRT in this model. The addition of CRLX101 to 5FU+XRT did not increase hematologic or skin toxicities. In the ongoing clinical trial, none of the first 3 patients enrolled (the first dosing cohort) have experienced dose limiting toxicities and 1 out of 3 patients had a pCR. Conclusions: CRLX101 has been shown in preclinical experiments to improve the therapeutic index of CRT for rectal cancer. Preliminary clinical data suggest that CRLX101+5FU+XRT treatment is well tolerated. Clinical trial information: NCT02010567.

6086 Background: Human immunodeficiency virus (HIV)-infected individuals are at increased risk for head and neck cancer (HNC). Poor survival is associated with low CD4 counts, larynx/hypopharynx si...