Immune checkpoint blockade has transformed the treatment of non-small cell lung cancer (NSCLC). However, a minority of patients achieve durable benefit with anti-PD-(L)1 standard of care even with high PD-L1 expression. Better treatments for patients with advanced NSCLC remain an unmet need. The IO102-IO103 vaccine is an investigational first-in-class, dual-antigen, immune-modulatory therapy that stimulates activation of T cells against IDO+ and/or PD-L1+ cells in cancer patients, resulting in modulation of the tumor microenvironment, rendering the tumor more susceptible to anti-PD-1 blockade.

Background: Immune checkpoint inhibitors are a standard therapy in metastatic urothelial carcinoma (UC). Long-term follow-up is necessary to confirm durability of response and identify further safety concerns. Patients and methods: In KEYNOTE-045, patients with metastatic UC that progressed on platinum-containing chemotherapy were randomly assigned 1:1 to receive pembrolizumab or investigator's choice of paclitaxel, docetaxel, or vinflunine. Primary endpoints were progression-free survival per RECIST version 1.1 by blinded independent central review (BICR) and overall survival. In KEYNOTE-052, cisplatin-ineligible patients with metastatic UC received first-line pembrolizumab. The primary endpoint was objective response rate per RECIST version 1.1 by BICR. Results: A total of 542 patients (pembrolizumab, n = 270; chemotherapy, n = 272) were randomly assigned in KEYNOTE-045. The median follow-up was 62.9 months (range 58.6-70.9 months; data cut-off 1 October 2020). At 48 months, overall survival rates were 16.7% for pembrolizumab and 10.1% for chemotherapy; progression-free survival rates were 9.5% and 2.7%, respectively. The median duration of response (DOR) was 29.7 months (range 1.6+ to 60.5+ months) for pembrolizumab and 4.4 months (range 1.4+ to 63.1+ months) for chemotherapy; 36-month DOR rates were 44.4% and 28.3%, respectively. A total of 370 patients were enrolled in KEYNOTE-052. The median follow-up was 56.3 months (range 51.2-65.3 months; data cut-off 26 September 2020). The confirmed objective response rate was 28.9% (95% confidence interval 24.3-33.8), and the median DOR was 33.4 months (range 1.4+ to 60.7+ months); the 36-month DOR rate was 44.8%. Most treatment-related adverse events for pembrolizumab in either study were grade 1 or 2 and manageable, which is consistent with prior reports. Conclusion: With w5 years of follow-up, pembrolizumab monotherapy continued to demonstrate durable efficacy with no new safety signals in patients with platinum-resistant metastatic UC and as first-line therapy in cisplatin-ineligible patients.Clinical trial registry and ID: With ClinicalTrials.gov NCT02256436 (KEYNOTE-045); https://clinicaltrials.gov/ct2/show/ NCT02256436 and NCT02335424 (KEYNOTE-052); https://clinicaltrials.gov/ct2/show/NCT02335424

EPI-7386 is a next generation aniten designed to inhibit androgen receptor (AR) activity by binding the N-terminal domain and blocking transcription despite resistance driven by point mutations and splice variants in the ligand-binding domain. In preclinical models, the combination of EPI-7386 with Enz results in a deeper blockade of the AR pathway and greater antitumor activity, prompting this trial. This phase I/II multicenter, open-label clinical trial (NCT05075577) is enrolling mCRPC patients on androgen deprivation therapy and naïve to second-generation antiandrogens (1 line of prior chemotherapy in the metastatic hormone sensitive setting allowed). PI examines escalating doses of EPI-7386 with Enz. Primary and secondary endpoints of PI evaluate the safety and pharmacokinetics (PK) of EPI-7386 and Enz when co-administered to establish recommended phase II combination doses (RP2CDs) and address possible drug-drug interactions (DDIs). Once RP2CDs are established, phase II (PII) will commence as a two arm, 2:1 randomized trial evaluating antitumor activity of EPI-7386 in combination with Enz versus Enz alone. To date, 11 patients have been enrolled in cohorts 1-3 (cohort 4 is currently enrolling). Safety is consistent with second-generation antiandrogens (e.g., Grade 1 or 2 AEs of fatigue and hot flashes). PK results demonstrate Enz exposure is minimally impacted by EPI-7386, allowing testing of the full dose of Enz (160 mg) in the current cohort 4. EPI-7386 exposure is strongly reduced by Enz (CYP3A4 inducer that metabolizes EPI-7386) but remains in the clinically relevant range seen in xenograft studies. EPI-7386 BID dosing shows an increase in EPI-7386 exposure and mitigates DDI caused by Enz. Data from the first 10 evaluable patients show 9/10 achieve a PSA90, and 7/10 patients reach PSA <0.2 ng/mL. With no safety concerns from cohorts 1-3, cohort 4 is currently enrolling at EPI-7386 BID + 160 mg QD Enz to evaluate optimal RP2Ds before the P2 component of the trial. Updated results, including cohort 4, will be presented.

First-line pembrolizumab monotherapy is a standard of care option in platinum-ineligible patients with advanced UC in the US. However, there is no standard definition of platinum ineligibility; treatment decisions are based on clinical judgment. It is of interest to determine whether efficacy of pembro in UC varies based on criteria used to define platinum ineligibility. This post hoc analysis pooled pts treated with pembro monotherapy from KEYNOTE-052 (N=370; NCT02335424) and LEAP-011 (N=242; NCT03898180) who were potentially platinum ineligible based on criteria determined by an extensive search of the literature. Candidate criteria for platinum ineligibility identified in the literature included ECOG PS 2, renal dysfunction (GFR <60 mL/min), visceral disease, and age ≥80 y. Subgroups of pts with several combinations of these criteria were selected for this analysis: ECOG PS 2 (with or without age ≥80 y, renal dysfunction, or visceral disease); age ≥80 y with renal dysfunction; or visceral disease (with or without age ≥80 y or renal dysfunction). Efficacy end points were ORR and OS. The database cutoffs were September 26, 2020 (KEYNOTE-052), and July 26, 2021 (LEAP-011); median (range) follow-up was 56.3 mo (51.2-65.3) and 7.0 mo (0.2-25.0), respectively. In the primary analyses, ORR (95% CI) was 28.9% (24.3-33.8) in KEYNOTE-052 and 28.9% (23.3-35.1) in the pembro monotherapy arm of LEAP-011; median (95% CI) OS was 11.3 (9.7-13.1) and 12.9 (9.8-17.8) mo, respectively. ORR ranged from 23.5%-33.3%, and median OS ranged from 9.0-10.6 mo among the subgroups (Table).Table: 1752PAge ≥80 y + renal dysfunction n=111ECOG PS 2 only n=355ECOG PS 2 + age ≥80 y n=87ECOG PS 2 + renal dysfunction n=176ECOG PS 2 + visceral disease n=285Visceral disease + age ≥80 y n=116Visceral disease + renal dysfunction n=307ORR, % (95% CI)27.9 (19.8-37.2)26.2 (21.7-31.1)33.3 (23.6-44.3)27.8 (21.4-35.1)23.5 (18.7-28.9)26.7 (18.9-35.7)25.7 (20.9-31.0)OS, median (95% CI), months10.6 (6.8-12.3)10.1 (8.6-11.7)9.3 (6.3-12.2)10.1 (8.6-13.8)9.1 (7.2-10.8)9.0 (6.1-11.3)10.6 (9.0-12.5)12-month OS, %43.344.340.545.240.235.445.2 Open table in a new tab In this post hoc exploratory analysis, responses to pembro monotherapy occurred regardless of the criteria used to define platinum ineligibility for pts with UC. Median OS was generally consistent among subgroups and was similar to the overall pt populations.

Cluster of differentiation 46 (CD46) is expressed at high level in CRPC and expression is further enriched upon androgen signaling inhibition (ASI) and in treatment-emergent small cell neuroendorcine prostate cancer (t-SCNC). FOR46 is a vc-MMAE antibody-drug conjugate that recognizes a tumor selective epitope of CD46. FOR46 binds to CD46 with high affinity and demonstrates anti-tumor activity in prostate cancer xenografts. A first-in-human study of safety and preliminary efficacy of FOR46 in mCRPC patients (pts) was undertaken.

In the phase 2 KEYNOTE-052 trial in advanced UC, 18-gene T-cell–inflamed gene expression profile (GEP) was positively associated with response to pembro and stromal sig (stroma/EMT/TGF-β) was negatively associated. We explored association of these sigs with efficacy in the phase 3 KEYNOTE-045 trial of pembro vs chemo in platinum-refractory metastatic UC (mUC). Univariate analyses using logistic regression (ORR) and Cox proportional hazard (PFS, OS), adjusted for ECOG PS, were performed, and nominal P values (1-sided, pembro; 2-sided, chemo) without multiplicity adjustment were calculated. Significance was prespecified at 0.05. Clinical utility of GEP and stromal sig was assessed using first tertile and median cutoffs. 291/542 pts (53.7%) had RNA-seq data. GEP was associated with ORR (P=0.05) with pembro; a positive trend was observed for PFS (P=0.09) and OS (P=0.12). GEP was not associated with ORR (P=0.87), PFS (P=0.58), or OS (P=0.98) with chemo. HR estimates using prespecified GEP cutoff suggest trends toward improved PFS and OS for pembro vs chemo in GEP-high group (Table). Stromal sig was not associated with outcomes with pembro (P=0.15 [ORR], 0.30 [PFS], 0.40 [OS]) or chemo (P=0.42 [ORR], 0.09 [PFS], 0.12 [OS]). HR estimates using prespecified stromal sig cutoff suggest trends toward longer PFS and OS in ≥median group; this may be driven by poor performance of chemo in this group vs the hypothesized association with pembro (Table). In this exploratory analysis in pts with mUC from KEYNOTE-045, GEP was positively associated with ORR to pembro but not chemo. GEP continues to serve as a good exploratory gene sig to support the MOA of pembro in highly inflamed tumors. Stromal sig was not associated with outcomes to pembro in KEYNOTE-045. Additional analyses are exploring differences in association of stromal sig with pembro between KEYNOTE-052 and KEYNOTE-045.Table 744PClinical outcomes by GEP and stromal signature cutoff in KEYNOTE-045GEP≥first tertileGEP≥first tertileGEP

Abstract Background: In mTNBC, anti-PD-1/L1 monotherapy is most effective when administered early in the course of disease, with recent trials demonstrating overall response rates (ORR) of 23-26% in the first-line setting and 5-6% in later lines. This may reflect iatrogenic lymphopenia from preceding cytotoxic chemotherapy. Furthermore, curative-intent chemotherapy is associated with prolonged suppression of naïve CD4+ cells, a T-cell subset that may play a critical role in the generation of de novo anti-tumor immune responses. We present the final clinical results of a pilot study evaluating the safety and efficacy of combining pembrolizumab plus standard-of-care capecitabine in the first/second-line mTNBC setting. We also explore potential associations between clinical benefit and lymphopenia, preceding chemotherapy, and absolute naïve CD4+ counts. Methods: In a pilot study, we evaluated the tolerability and preliminary efficacy of concurrent pembro (200mg IV q21 day) plus investigator-selected 1st/2nd line paclitaxel (80mg/m2 IV weekly) or oral cape (2,000mg BID, weekly 1 on/1 off). The primary endpoint was tolerability, defined as the proportion of subjects receiving >6 weeks concurrent therapy without dose discontinuation with toxicities reported per CTCAE v4.0. The secondary endpoint was 12-week objective response rate (ORR) by RECIST1.1. Exploratory endpoints included peripheral blood cell enumeration by real-time flow cytometry and routine clinical laboratory. Naïve CD4+ cells were defined as CD45+ CD3+ TCRab+ CD4+ CD45RA+ CCR7+. Here, we report the results of the pilot phase of the cape cohort (NCT02734290). Results: Twelve of 14 subjects were treated in the first-line setting. All subjects (14/14, 100%) tolerated cape+pembro for >6 weeks, with toxicities consistent with monotherapy cape experience (diarrhea: grade I-II 50%, grade III 7%; hand-foot: grade I-II 71%) that improved with dose-reduction as needed. At 12 weeks, the ORR was 6/14 (42.9%), and the clinical benefit rate (ORR + stable disease) was 8/14 (57.1%). Depressed absolute lymphocyte count at baseline (ALC<1.0/uL: 33% CBR; ALC≥1.0/uL: 75% CBR) and recent exposure to cytotoxic chemotherapy (<6 months: 33% CBR; >6 months: 75% CBR) were associated with reduced clinical benefit. By flow cytometry, subjects experiencing clinical benefit had higher baseline absolute naïve CD4+ counts (average 283 cells/uL v. 93 cells/uL, p=.069). Conclusions: This study met the primary endpoint of safety for cape plus pembro in mTNBC, with encouraging clinical activity. These data are supportive of further studies evaluating combination chemotherapy plus anti-PD-1/L1 mTNBC. We observed greater clinical benefit in subjects with non-suppressed ALC, less exposure to recent chemo, and higher baseline naïve CD4+ counts, suggesting that iatrogenic immunosuppression can impair response to immune checkpoint therapy in mTNBC. These findings should be confirmed in ongoing randomized trials of immune checkpoint +/- chemotherapy in mTNBC, and should be considered in the design of future clinical trials. Citation Format: Page DB, Pucilowska J, Bennetts L, Kim I, Sanchez K, Martel M, Conlin A, Moxon N, Mellinger S, Acheson A, Kemmer K, Mitri Z, Vuky J, Ahn J, Abaya C, Manigault T, Basho R, Urba WJ, McArthur HL. Updated efficacy of first or second-line pembrolizumab (pembro) plus capecitabine (cape) in metastatic triple negative breast cancer (mTNBC) and correlations with baseline lymphocyte and naïve CD4+ T-cell count [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-03.

KEYNOTE-052 (NCT02335424), an open-label, multicenter, phase 2 study, evaluated the efficacy and safety of pembro in first-line cisplatin-ineligible pts with u/m UC. 374 pts have been enrolled. Eligibility included pathologically confirmed and measurable u/m UC, age ≥18 y, no chemotherapy for u/m disease, ECOG PS 0-2, and cisplatin ineligibility (ECOG PS 2, creatinine clearance <60 mL/min, ≥ grade 2 neuropathy or hearing loss, NYHA class III CHF). Pts received pembro 200 mg Q3W until progressive disease, unacceptable toxicity, or 24 mo of treatment. Primary end point was RECIST v1.1 confirmed objective response rate (ORR) by independent review in all pts and in PD-L1–positive pts by combined positive score (CPS) (tumor and immune cell PD-L1 expression). Secondary objective was to determine the CPS-high biomarker cutpoint. Interim analysis was planned to evaluate ORR for the first 100 pts and to determine the CPS-high cutpoint. Median age was 75 years (13% ≥85). 13% received perioperative chemotherapy. 87% had visceral disease. 46% were ECOG 2/3. 45% were cisplatin ineligible because of renal insufficiency only. 11% were cisplatin ineligible because of ECOG 2 performance status and renal insufficiency. The CPS-high cutpoint was determined to be ≥10% PD-L1 expression. As of 6/1/16, data cutoff (median 8 mo follow-up), ORR was as follows:Tabled 1% (95% CI)All subjects N = 100CPS ≥1% N = 63CPS ≥10% N = 30ORR24.0 (16.0-33.6)25.4 (15.3-37.9)36.7 (19.9-56.1)CR6.0 (2.2-12.6)6.3 (1.8-15.5)13.3 (3.8-30.7) Open table in a new tab Median duration of response (DOR) has not been reached (range, 1.4+ - 9.8+ mo). DOR rate ≥6 months was 83% (Kaplan-Meier estimate). 67% of pts experienced a drug-related adverse event (DRAE), most commonly fatigue (14%). 16% experienced a grade 3/4 DRAE. 5% discontinued therapy because of a DRAE. Pembro 200 mg Q3W demonstrates substantial antitumor activity and has a manageable toxicity profile in cisplatin-ineligible pts with u/m UC. CPS high cutpoint was determined to be ≥10% PD-L1 expression. CR rate of 6% for all pts and 13.3% for pts CPS ≥10% is encouraging.

9027 Background: Hot flashes (HFs) occur in approximately 2/3 of androgen-deprived men. There is limited data on treatment from prospective intervention studies. METHODS Eligible androgen-deprived men were randomly assigned to 1 of 4 daily regimens (2x2 factorial design) for 12 weeks: placebo pill and casein protein (P), soy protein and placebo pill (S), venlafaxine (Effexor) and Casein Protein (E), or soy plus venlafaxine (SE). The primary endpoint was hot flash symptom severity score (HFSSS), defined as number x severity of hot flashes. The secondary endpoint was quality of life (QoL), assessed using the FACT-P. RESULTS 120 men aged 46-91 (median 69 years) participated. Most were Caucasian (78%) and overweight obese (83%). Groups were similar at baseline (BL). Treatment compliance was 88%. Toxicity was minimal. All groups showed a reduction in HFSSS, but there were no significant differences between groups (Table). QoL did not change significantly over time and did not differ between groups. CONCLUSIONS In androgen-deprived men, neither venlafaxine nor soy protein had a significant effect on HFSSS or QoL, in contrast to findings from Quella et al (1999), which reported a 54% decrease in HF score in men taking venlafaxine. Supported by CCOP Research Base Grant 5 U10 CA081851-11. [Table: see text].

CRA9015 Background: Hot flashes are a common symptom during the menopause transition or following breast cancer treatment that can negatively impact the quality of life for many women. Preliminary data have suggested that flaxseed, a rich source of dietary lignans, may be a potentially effective treatment for hot flashes. Methods: A phase III randomized, placebo controlled trial was conducted to evaluate the efficacy of flaxseed in reducing hot flashes. Postmenopausal women were randomly assigned to a flaxseed bar (providing 410 mg of lignans) for 6 weeks vs a placebo bar. Participants completed daily prospective, self report hot flash diaries during the baseline week and then began eating one study bar per day for 6 weeks, while continuing to record their daily hot flashes. The intra-patient difference in hot flash activity between baseline and the last treatment week was the primary endpoint. Side effects of the bars were evaluated through self report and CTC assessment. Results: Between October and December 2009, 188 women were enrolled onto this trial. Mean hot flash scores were reduced by 4.9 units in the flaxseed group and 3.5 in the placebo group (p=0.29). In both groups, a little over a third of the women received a 50% reduction in their hot flash scores. Only one side effect was significantly different between groups, that being grade 1 pruritis, which was more common (7%) in the placebo group versus 1% in the flaxseed group. Both groups reported increased abdominal distension, flatulence, diarrhea and nausea. Adherence and ability to detect treatment assignment did not differ between groups. Conclusions: The results of this trial do not support the use of 410 mg of flaxseed lignans for the reduction of hot flashes. The gastrointestinal side effects seen in both groups were likely due to the fiber content in the flaxseed and placebo bars.

5551 Background: Patients (pts) with platinum refractory OC have limited treatment options. Bevacizumab, an anti- angiogenesis agent has demonstrated efficacy in recurrent ovarian cancer. Bevacizumab combined with chemotherapy in other solid tumors has improved efficacy compared with bevacizumab or chemotherapy alone. Topotecan, an active drug in recurrent OC has been used in a weekly fashion with less toxicity and more acceptability than a standard 5 day regimen. Topotecan and bevacizumab have non-overlapping toxicities. We studied the efficacy and tolerability of weekly topotecan and bevacizumab in patients with platinum refractory OC. Methods: The primary objectives of this study were to evaluate time to progression, overall survival, response rate and toxicity of this combination regimen. Eligible pts included those with platinum refractory OC (recurrence < 6 months of platinum therapy) who had received a maximum of 2 prior chemotherapy regimens. Pts had measurable disease or elevated CA-125 (>100). Treatment regimen was topotecan: 4 mg/m2 day 1, 8, 15 and bevacizumab: 10 mg/kg IV day 1, 15 of a 28 day cycle. Treatment continued until progression or severe toxicity. Results: Twenty-two pts have been enrolled to date, with 11 remaining on study and 18 now evaluable. Best responses for the 18 evaluable pts were: 22.2% partial response (n=4), 27.8% stable disease (n=5), and 50% progressive disease (n=9). Eleven pts went off study due to progressive disease (based on CT scan RECIST criteria [n=6] or general deterioration and/or bowel obstruction [n=5]). Median duration on study for the 18 evaluable pts was 15 wks (5–63). Four pts have had progression free survival >5 months. The 18 evaluable pts received a total of 91 treatment cycles. No pt went off study due to treatment related toxicity or suffered a bowel perforation. Conclusions: Combination bevacizumab and topotecan administered in a weekly fashion demonstrate good activity in platinum refractory OC with acceptable toxicity. G3–4 Hematologic or Hypertensive Toxicities (n=18 evaluable pts) Toxicity Treatment cycles (n=91) with toxicity: n (%) Pts with toxicity: n (%) G3 thrombocytopenia 1 (1.1 ) 1 (5.5)* G3 leukopenia 2 ( 2.2) 2 (11.1)* G4 leukopenia 1 ( 1.1) 1 (5.5) G3 hypertension 3 (3.3 ) 3 (16.7) All G3–4 7 (7.7) 6 (33.3) * one pt had both toxicities in one cycle No significant financial relationships to disclose.

3520 Background: IGF1R is a receptor tyrosine kinase which is overexpressed in many primary tumor cells, including breast, colon, lung and prostate cancers. Activation of this signaling pathway induces mitosis, is required to establish and maintain a transformed phenotype, and protects cells against apoptosis. MK-0646 is a humanized IgG1 monoclonal antibody that binds to IGF-1R and is being developed for the treatment of cancer. Methods: In Parts 1 and 2, patients were treated with loading doses of MK-0646 from 2.5 - 20.0 mg/kg (mpk) followed by maintenance doses from 2.5 - 15.0 mpk IVq2W. In Part 3, patients will be treated at a 15 mpk loading dose and 10 mpk maintenance dose. The objectives of the study are to determine safety and tolerability, formation of human anti-MK-0646 antibodies, pharmacokinetics (PK), and tumor response. Results: 29 patients (M/F 22/7), with a median age of 62 yrs (range 23–84) were treated. The median number of days on treatment was 64 (range 14 to >351). Two patients have remained on study greater than 1 yr. One dose limiting toxicity (Gr 4 thrombocytopenia) was observed at the 15.0 mpk loading 5.0 mpk maintenance cohort. Adverse events include fatigue (9), vomiting, nausea, constipation (8 each), and diarrhea, weight loss, abdominal pain (7 each). PK analyses suggest that mean MK-0646 serum concentration following the loading dose decline at least biexponentially after peak; the terminal half-life averaged approx. 100 hours (range 54–296). The clearance (CL) for the loading dose was relatively unchanged at doses of 10 mpk and higher. Conclusions: MK-0646 appears to be well tolerated at loading doses up to 20 mpk and maintenance doses up to 15 mpk. Constant CL for loading doses higher than 10 mpk suggests saturation of IGF1R receptors. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Merck Merck

To evaluate the toxicity and PSA response in patients treated on a Phase II trial of bevacizumab in combination with androgen deprivation and IMRT for high-risk prostate cancer. All patients met criteria for high-risk prostate cancer with clinical Stage T2b-4 or Gleason sum score 8-10 or PSA >20 and Gleason sum score ≥7. Treatment consisted of bicalutamide (50 mg /day for a total of 16 weeks), goserelin (10.8 mg q3 months for a total of 2 years), and bevacizumab (10 mg/kg every 2 weeks for the first 16 weeks, then 15 mg/kg every 3 weeks for 12 weeks) starting 8 weeks prior to IMRT and continuing through the duration of IMRT. The IMRT dose is 77.9 Gy to the prostate, 64.6 Gy to seminal vesicles, and 57 Gy to the pelvic lymph nodes in 38 fractions. Target localization was achieved with three implanted gold fiducials or electromagnetic transponders (Calypso). All toxicities are graded according to the NCI CTC version 3. From April 2006 to December 2007, 18 patients have enrolled with a median follow-up of 12 months (range, 5-22 months). Median age is 69 (range, 50-83). Median Gleason score is 8 (range, 7-9). Median pretreatment PSA is 11.2 ng/mL (range, 3.2-240). All patients have completed IMRT, median of 8.5 months from last day of treatment (range, 1.5-18.5). Grade 2 toxicities include hypertension (11), diarrhea (1), headache (1), fatigue (2), hemorrhoids (1), elevated bilirubin (1), leukopenia (5), cystitis (1), urinary frequency (1), and proteinuria (6). Grade 3 toxicities include elevated liver function tests (1), hyponatremia (1), hypertension (3), proteinuria (1), fatigue (1), and urinary frequency (1). There were no Grade 4 or 5 toxicities; and no bleeding or thrombotic complications. All patients responded to treatment and the median current PSA level is 0.01 ng/mL (range, <0.01-0.18). All patients continue to have stable or declining PSA levels. Thus far, this regimen is well tolerated. Bevacizumab does not appear to exacerbate acute radiation toxicities. We will continue to follow patients to assess long-term toxicity and efficacy of treatment.

Objective. Patients (pts) with platinum refractory OC have limited treatment options. Bevacizumab, an anti-angiogenesis agent has demonstrated efficacy in recurrent OC. Bevacizumab combined with chemotherapy in other solid tumors has improved efficacy compared with bevacizumab or chemotherapy alone. Topotecan, an active drug in recurrent OC has been used in a weekly fashion with less toxicity and more acceptability than a standard 5 day regimen. Topotecan and bevacizumab have non-overlapping toxicities. We studied the efficacy and tolerability of weekly topotecan and bevacizumab in patients with platinum refractory OC. The primary objectives of this study were to evaluate time to progression, overall survival, response rate and toxicity of this combination regimen.