ASCO 2013 Abstract Roundup

May 16, 2013

Abstracts published in the Annual Meeting Proceedings Part I featuring late-stage data on ibrutinib, eribulin, regorafenib, sipuleucel-T, lambrolizumab, palbociclib, and more.

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Preliminary safety and efficacy of IPI-145, a potent inhibitor of phosphoinositide-3-kinase-δ,γ, in patients with relapsed/refractory lymphoma.

A real-world study on implementation of new therapeutic options, especially bevacizumab, in a cohort of HER2-negative metastatic breast cancer patients treated with first-line chemotherapy.

A randomized phase II trial of sipuleucel-T with concurrent or sequential abiraterone acetate (AA) plus prednisone (P) in metastatic castrate-resistant prostate cancer (mCRPC).

A randomized phase II study evaluating the optimal sequencing of sipuleucel-T and androgen deprivation therapy (ADT) in biochemically recurrent prostate cancer (BRPC): Immune results.

Open-label, multicenter study of sipuleucel-T in men with metastatic castrate-resistant prostate cancer (mCRPC) previously treated with sipuleucel-T: Evaluation of antigen presenting cell (APC) activation and ELISPOT data.

Use of tumor genomic profiling to reveal mechanisms of resistance to the BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL).

An open-label phase II study of ibrutinib in patients with refractory follicular lymphoma.

A randomized, multicenter, open-label, phase III study of the Bruton tyrosine kinase (BTK) inhibitor ibrutinib (PCI-32765) versus ofatumumab in patients (pts) with relapsed or refractory (RR) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): RESONATE.

Clinical efficacy and safety of lambrolizumab (MK-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma.

A randomized, multicenter, double-blind phase III study of palbociclib (PD-0332991), an oral CDK 4/6 inhibitor, plus letrozole versus placebo plus letrozole for the treatment of postmenopausal women with ER(+), HER2(—) breast cancer who have not received any prior systemic anticancer treatment for advanced disease.

Exposure—efficacy relationship of trastuzumab emtansine (T-DM1) in EMILIA, a phase III study of T-DM1 versus capecitabine (X) and lapatinib (L) in HER2-positive locally advanced or metastatic breast cancer (MBC).

IPI-145 was well tolerated and showed clinical activity in patients with relapsed/refractory advanced B- and T-cell lymphoma across the range of doses examined. The single agent maximum tolerated dose has not been determined and dose escalation continues. Updated safety and efficacy data from patients with lymphoma enrolled in dose escalation or expansion cohorts evaluating 25 mg twice daily and a higher dose (< maximum tolerated dose) of IPI-145 will be presented.The real world uptake of bevacizumab was lower than expected and was offered to a selected population. Patient selection differed from the EMA registration trial, which may explain the lower progression-free survival. The study's authors recommend the use of broader inclusion criteria in future clinical studies and/or more strict adherence to these criteria in daily practice to guarantee effective implementation of new drugs.These data suggest sipuleucel-T can be successfully manufactured during concurrent abiraterone acetate + prednisone. Product potency and prime boost effect were similar to sipuleucel-T alone. Immune responses and adverse events were similar in both arms. It is not known if sipuleucel-T will provide similar efficacy with concurrent or sequential abiraterone acetate + prednisone.While confirmation is required, these preliminary data suggest that tumor-specific T cell responses and broad based immune responses are augmented when sipuleucel-T is given after rather than before ADT initiation. These data are consistent with preclinical studies showing that ADT enhances T cell activity, and provide preliminary evidence that combining ADT with sipuleucel-T may augment adaptive immunity. Further follow up will determine whether augmented immune responses correlate with clinical parameters (eg PSA recurrence).This is the first trial to report the feasibility of sipuleucel-T retreatment following treatment in an earlier stage of prostate cancer. These data indicate the presence of existing immunological memory to the immunizing antigen several years after initial treatment. In addition, retreatment with sipuleucel-T appeared to boost product potency compared with prior treatment.Although rare, the acquisition of C481S BTK and R665W PLCg2 mutations in the setting of resistance confirms BTK as an important pharmacologic target of ibrutinib, and suggests mechanisms of ibrutinib resistance.The study aims to enroll 110 patients with chemoimmunotherapy-resistant follicular lymphoma. Patients will receive an oral daily dose of 560 mg ibrutinib. Patients must have been treated with at least 2 prior lines of therapy, at least 1 rituximab-containing combination chemotherapy regimen, and the last prior line of therapy included an anti-CD20 monoclonal antibody-containing chemotherapy regimen. The primary objective of the study is to evaluate the ORR (CR + PR), with secondary objectives of duration of response, progression-free survival, overall survival, and safety.The study is enrolling 350 planned pts in 9 countries. Pts are randomized 1:1 to receive ibrutinib 420 mg orally once daily or ofatumumab per the package insert at 300 mg for the first dose, then 2000 mg for a total of 12 doses over 24 weeks. Pts are stratified based on del 17p and disease refractory to purine analogs.Programmed death-1 (PD-1) is an inhibitory T-cell co-receptor that may lead to suppression of antitumor immunity. Lambrolizumab is a humanized monoclonal IgG4 antibody against PD-1. Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated melanoma patients. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated melanoma.Based on phase II data, a global, randomized, double-blind, phase III clinical trial was designed to demonstrate that palbociclib + letrozole provides superior clinical benefit compared with letrozole + placebo in postmenopausal women with ER(+), HER2(—) ABC who have not received any prior systemic therapy for their advanced disease. The study aims to assess whether palbociclib + letrozole improves median PFS over letrozole at HR of at least 0.7.In EMILIA, no clear trends were observed between T-DM1 exposure and PFS, OS, or ORR, following administration of T-DM1 3.6 mg/kg q3w. However, there was a suggestion of improved OS HR by stratified T-DM1 Cquartiles, albeit with mostly overlapping 95% CIs. Ongoing T-DM1 clinical trials will further evaluate this potential relationship.Phase II study of eribulin mesylate as first- or second-line therapy for metastatic HER2-negative breast cancer.Eribulin mesylate is a nontaxane microtubule dynamics inhibitor that is approved in patients with metastatic breast cancer who have previously received at least two chemotherapeutic regimens (including an anthracycline and a taxane) for metastatic breast cancer. This study is phase II, multicenter, open-label, single-arm in patients with HER2-negative metastatic breast cancer who have been treated with chemotherapeutic regimens including an antheracycline and a taxane. Eribulin mesylate (1.4mg/m2) will be given on days 1 and 8 of each 21-day cycle. The primary endpoint is objective response rate, and secondary endpoints include duration of response, progression-free survival, overall survival, the safety of the treatment, and quality of life.A phase III, open-label, randomized study of eribulin mesylate versus capecitabine in patients with locally advanced or metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes: Subgroup analyses.In addition to patients with triple-, ER-, or HER2-negative disease, further pre-specified exploratory analyses suggest that other patient subgroups may particularly benefit from treatment with eribulin; further studies are warranted to address these hypotheses.Phase I/II dose-escalation study of daratumumab in patients with relapsed or refractory multiple myeloma.Daratumumab induced a marked reduction in paraprotein and bone marrow plasma cells at doses &ge;4mg/kg in heavily pretreated relapsed or refractory multiple myeloma patients. In addition, high response rates and encouraging PFS data were observed. This is unprecedented for single-agent mAb treatment of multiple myeloma.Regorafenib (REG) in patients with hepatocellular carcinoma (HCC) progressing following sorafenib: An ongoing randomized, double-blind, phase III trial.Sorafenib is the accepted first-line systemic therapy for HCC, but no standard option is available for patients with tumor progression following sorafenib. This randomized, double-blind, placebo-controlled, multinational study will assess the efficacy and tolerability of regorafenib vs placebo in patients with HCC that has progressed following sorafenib treatment. The primary endpoint is OS; secondary endpoints are TTP, progression-free survival, tumor response, and safety.Cetuximab biweekly plus mFOLFOX6 as first-line therapy in patients (pts) with KRAS wild-type (wt) metastatic colorectal cancer (mCRC): An interim analysis of the CEBIFOX trial.This pre-specified interim analysis supports efficacy and safety of biweekly cetuximab given in combination with mFOLFOX6 in patients with mCRC. A high rate of objective responses and secondary hepatic resections was achieved. Based on these results enrolment in CEBIFOX is continued.Cetuximab with or without sorafenib in recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).Both arms demonstrated clinical activity although no significant difference was observed. However, a subset of patients with p16 neg tumors or low serum TGFB1 may have a greater benefit with cetuximab-based therapy.

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