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TPS1110 Background: There are currently no curative treatments for patients with metastatic triple-negative breast cancer (mTNBC), and prognosis for this disease is very poor. Emerging treatment combinations of anti-programmed death ligand 1 (PD-L1) agents with chemotherapy have shown promise in mTNBC. SGN-LIV1A, or ladiratuzumab vedotin (LV), is a novel investigational humanized IgG1 antibody-drug conjugate (ADC) directed against LIV-1, which is highly expressed in breast cancer cells. LV mediates delivery of monomethyl auristatin E (MMAE), which drives antitumor activity through cytotoxic cell killing and induces immunogenic cell death (ICD). Preliminary results from an ongoing phase 1 study of LV monotherapy has shown LV to be well tolerated and to have encouraging antitumor activity in patients with mTNBC. Combining LV and pembrolizumab may result in complementary, as well as synergistic, activity through LV-induced ICD that creates a microenvironment favorable for enhanced anti-PD-L1 activity. Methods: This single-arm, open-label, phase 1b/2 study evaluates the safety and antitumor activity of LV in combination with pembrolizumab as first-line therapy for patients with unresectable locally advanced or mTNBC (NCT03310957, 2017-002289-35). Patients must have measureable disease per RECIST v1.1, an ECOG score of 0 or 1, and no prior cytotoxic or anti-PD-L1 treatment for advanced disease. This study has 2 parts that are enrolling sequentially: a dose-finding phase that starts at LV 2.5 mg/kg + pembrolizumab 200 mg intravenously every three weeks, and a dose expansion phase. The primary objectives are to evaluate the safety/tolerability and objective response rate of LV + pembrolizumab, and identify the recommended phase 2 dose of LV. The secondary objectives are to assess duration of response, disease control rate, progression-free survival, and overall survival. Additional objectives include assessing PD-L1 and LIV-1 expression-response relationship. Study enrollment is ongoing in the US and EU. Clinical trial information: NCT03310957.

LBA1000 Background: The primary aims were to determine whether adjuvant DD AC→PG will be superior to DD AC→P as well as to TAC in DFS and to compare the relative DFS of TAC and DD AC→P. Secondary endpoints include survival and toxicity. Methods: From Nov 3, 2004 to May 3, 2007, 4894 women were randomized; 1630 to TAC (docetaxel [T] 75 mg/m2, doxorubicin [A] 50 mg/m2, cyclophosphamide [C] 500 mg/m2 q3 wks x 6), 1634 to DD AC→P (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 followed by P 175 mg/m2 q2 wks x 4), and 1630 to DD AC→PG (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 → P 175 mg/m2 + G 2000 mg/m2q2 wks x 4). Primary G-CSF support was required and erythropoiesis-stimulating agents (ESA) were used at investigator discretion. 52% were postmenopausal, 65% had 1 - 3 positive nodes, and 80% had HR+ breast cancer. Log-rank tests were used for pair-wise comparisons of the primary (DFS) and secondary (OS) endpoints among the three treatment arms. Results: With 64 months median follow-up, 5-year DFS in DD AC→PG group was 80.6% compared with 82.2% in DD AC→P group (HR=1.1; p=0.27) and 80.1 % (HR=0.97; p=0.71) in TAC group. 5-year OS was 90.8% in DD AC→PG group as compared with 89.1% (HR=.89; p=0.25) in DD AC→P group and 89.6 % (HR=0.90; p=0.32) in TAC group. HR for DFS and OS of DD AC→P vs. TAC were 0.89 (p=0.14) and 1.01 (p=0.92) respectively. Toxicities for TAC, DD AC→P, DD AC→PG, respectively: febrile neutropenia (Gr 3/4: 9%, 4%, 4% [p

e18122 Background: The trial was designed to examine PFS, OS and toxicities of a novel 3 drug combination in advanced NSC lung cancer. The first patient was entered 3/08 and the last in 5/11. Methods: Treatment consisted of Carboplatin AUC 5,Pemetrexed %00mg/m2, Bevacizumab 15mg/kg q21d x 6 cycles; then Bev maintenaince q3wk for up to one year. Eligibile pts. had metastatic non-squamous NSC lung ca, EGOG 0-1, first line Rx. Fifty patients were entered, all available for response and toxicity analysis: 26 M, median age 64, 45 white. Results: 52% RR by RECIST (2% CR, 50% PR); 26% SD. Median PFS 24 wks; median overall survival will be in excess of 49 weeks. 62% of patients received all planned 6 cycles and went on to maintenance. Treatment was out-patient and well tolerated with modest toxicities, including 2 DVT's, one PE, one TIA and one episode of F+N Conclusions: The 3 drug combination of Carboplatin, Pemetrxed and Bevacizumab for met NSC lung cancer is effective and well tolerated; and is a resonable choice of Rx for patients with non-squamous tumors hoping to avoid more neurotoxic or myelotoxic options.

LBA1000 Background: The primary aims were to determine whether adjuvant DD AC→PG will be superior to DD AC→P as well as to TAC in DFS and to compare the relative DFS of TAC and DD AC→P. Secondary endpoints include survival and toxicity. Methods: From Nov 3, 2004 to May 3, 2007, 4894 women were randomized; 1630 to TAC (docetaxel [T] 75 mg/m2, doxorubicin [A] 50 mg/m2, cyclophosphamide [C] 500 mg/m2 q3 wks x 6), 1634 to DD AC→P (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 followed by P 175 mg/m2 q2 wks x 4), and 1630 to DD AC→PG (A 60 mg/m2 and C 600 mg/m2 q2 wks x 4 → P 175 mg/m2 + G 2000 mg/m2q2 wks x 4). Primary G-CSF support was required and erythropoiesis-stimulating agents (ESA) were used at investigator discretion. 52% were postmenopausal, 65% had 1 - 3 positive nodes, and 80% had HR+ breast cancer. Log-rank tests were used for pair-wise comparisons of the primary (DFS) and secondary (OS) endpoints among the three treatment arms. Results: With 64 months median follow-up, 5-year DFS in DD AC→PG group was 80...

9016 Background: There is a lack of research to support interventions that may be effective in improving quality of life and sexual function disorders in female cancer survivors. L-arginine/Korean ginseng/gingko biloba/damiana-based supplement (ArginMax) contains L-arginine, which enhances systemic nitric oxide synthesis, resulting in vasodilation that may improve sexual function. Methods: This was a 12 week, randomized, placebo controlled trial. Eligible patients were females at least 6 months from active treatment and without current evidence of cancer. All patients took 3 capsules two times daily (6 total/day) and kept pill diaries. The primary outcome measure was the Female Sexual Function Inventory (FSFI) while the secondary outcome measure was the FACT-G quality of life instrument. Assessments including toxicities were made at baseline, 4, 8, and 12 weeks. Results: 186 patients were accrued to this trial between 5/10/07 and 3/24/10. Ages ranged from 23 to 79 with a median of 50 years. 76% of the par...

12018 Background: The primary endpoint of this prospective phase I study of DOX-TOP in pts with advanced solid tumors was to identify the maximum tolerated dose and dose-limiting toxicities (DLT) of this combination. Other objectives included a description of additional toxicities and efficacy in this patient population with refractory cancers. Pharmacokinetic sampling of TOP plasma levels will be reported separately. Methods: Eligible pts had advanced solid tumors and had either failed standard chemotherapy (chemo) or were pts for whom no standard therapy existed. They had ECOG PS = 0–2, adequate organ function, and gave written, informed consent. Initial doses included DOX 40 mg/m2 day 1 and TOP 2 mg/m2 days 1, 8 and 15 q 28 days. TOP was to be escalated in cohorts of pts. DLT was defined as febrile neutropenia, grade 4 thrombocytopenia, any grade 3 non-hematologic toxicity, or the inability to receive subsequent treatment due to ongoing toxicity. Treatment was held for ANC < 1000 or platelets < 75,000. Results: Fourteen pts have been enrolled on this phase I study, all of whom were evaluable for toxicity. There were 12 males and 2 females, and the median age was 57 years (range 25–86). Four had ECOG PS = 0, 9 had PS = 1, and 1 had PS = 2. Cancer types included head and neck (3), renal (2), and breast, pancreas, liver, esophagus, germ cell tumor, sarcoma, and others (one each). In the 6 pts treated at dose level 1, toxicities included grade 3 anemia (1) and neutropenia (2), and grade 4 neutropenia (1). DLT consisted of grade 4 thrombocytopenia (1) and inability to deliver day 15 TOP in 3/6 pts at this dose. Thus, TOP was reduced to 1.5 mg/m2 weekly for dose level -1, and 8 pts have been treated. Toxicities included grade 3 anemia (1)and neutropenia (2), and grade 4 neutropenia (1) and thrombocytopenia (1). Enrollment continues at this dose level to confirm tolerability. No patient achieved an objective response to therapy, but 2 pts have stable disease for up to 4 cycles. Conclusions: DOX-TOP can be safely combined in pts with advanced solid tumors, with hematologic toxicity as the DLT. The preliminary recommended phase II dose is DOX 40 mg/m2 and TOP 1.5 mg/m2. We plan to explore an additional dose level of DOX 30 mg/m2 and TOP 2 mg/m2. Phase II evaluation is contemplated in selected tumor types. [Table: see text]

4649 Background: D/E is a known active regimen in HRPC with an associated prolongation of survival. Exisulind induces apoptosis and in a double blind trial in men failing prostatectomy (RP) suppressed the increase in prostate specific antigen (PSA). Methods: Eighty men with chemotherapy-naive HRPC were enrolled in a multi-institutional trial from December 2002 to January 2004. Treatment consisted of E-280 mg po TID for days 1–5, D 70 mg/m2 on day 2, exisulind 250 mg po BID daily. Dexamethasone 8 mg po BID for days 1–3, and warfarin 2 mg po daily. The primary endpoints were time to objective progression (TTOP) and response rate (objective and post-therapy PSA). An increase in expected TTOP of 11 to 13.5 months would warrant further study. Results: The median age was 69.5, with a median number of years since diagnosis of 4 years. ECOG PS was 0 in 46%, 1 in 48%and 2 in 6%. The median baseline PSA was 152 ng/mL. The Gleason Score of the primary tumor was 8–10 in 59% and 5–7 in 41%. Sites of disease were visce...

6102 Background: In June 2002 the Helen F. Graham Cancer Center (HFGCC) at Christiana Care Health Services (CCHS) opened its doors to establish the multi-disciplinary team approach for cancer care....