Results of Phase 1a/1b Study of AbbVie's Investigational Medicine Rovalpituzumab Tesirine (Rova-T) Showed Overall Response Rate of 39 Percent in Pretreated Patients with Biomarker-Defined Small Cell Lung Cancer (SCLC)

NORTH CHICAGO, Ill., June 5, 2016 /PRNewswire/ -- AbbVie (NYSE: ABBV), a global biopharmaceutical company, today announced that treatment with rovalpituzumab tesirine (Rova-T), a delta-like protein 3 (DLL3)-targeted antibody-drug conjugate (ADC), demonstrated a confirmed overall response rate (ORR) of 39 percent and clinical benefit rate (stable disease or better) of 89 percent in patients with recurrent or refractory small cell lung cancer (SCLC), identified with high expression of DLL3. Rova-T demonstrated a one-year overall survival (OS) rate of 32 percent in the recurrent/refractory second- and third-line patient population. These new data were presented at the 52^nd Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago and featured in the "Best of ASCO" program, which presents scientific and educational highlights from the meeting. Less than one percent of all data abstracts are selected for this program.

In the trial, the most common treatment-emergent adverse events were fatigue (35 percent), pleural effusion (31 percent), edema peripheral (27 percent), nausea (19 percent), hypoalbuminemia (18 percent), thrombocytopenia, rash maculo-papular and decreased appetite (16 percent each). Grade three and higher severe toxicities were thrombocytopenia (11 percent), pleural effusion (8 percent), fatigue (4 percent), edema peripheral, and rash maculo-papular (3 percent each).

"These data further contribute to our understanding of the potential impact that treatment with Rova-T, a predictive biomarker-based therapy, could have on pretreated small cell lung cancer patients identified as high expressers of DLL3," said Charles M. Rudin, M.D., Ph.D., Chief of the Thoracic Oncology Service at Memorial Sloan Kettering. "The results presented at ASCO support further clinical development of this compound." 

Small cell lung cancer (SCLC) is an aggressive, difficult-to-treat form of cancer that accounts for roughly 13-15 percent of all lung cancers.^1,2 The five year survival rate for extensive-stage SCLC remains at less than 5 percent³ and there are limited treatment options available for the more than 234,000 people diagnosed with SCLC annually.^1,2,4 Treatment options for patients remain limited, with chemotherapy and radiation being the most common forms of first- and second-line treatment.⁵

"Due to the aggressive nature of small cell lung cancer, there are limited treatment options available, resulting in a typically poor prognosis for most patients," said Mike Severino, M.D., executive vice president of research and development and chief scientific officer, AbbVie. "Rova-T represents a potential new approach to treating this disease by targeting DLL3, a protein that is expressed in the majority of small cell lung cancer patients. We are committed to further developing this compound and look forward to the possibility of delivering it to patients in need of new treatment options." 

About the Phase 1a/1b Trial
This Phase 1a/1b, multicenter, open label, dose escalation trial was designed to assess the safety, pharmacokinetics, and preliminary efficacy of rovalpituzumab tesirine (Rova-T) as monotherapy in patients with recurrent small cell lung cancer (SCLC). The trial enrolled 74 patients, all of whom had failed at least one prior standard therapy. The primary objectives were maximum tolerated dose and an overall response rate (ORR), assessed by Response Evaluation Criteria In Solid Tumors (RECIST). Secondary objectives included pharmacokinetics and RECIST-assessed progression-free survival (PFS) and overall survival (OS). As well, the clinical benefit rate (stable disease or better) was assessed by RECIST.

About Rovalpituzumab Tesirine (Rova-T)
Rova-T is an investigational antibody-drug conjugate targeting the cancer-stem cell-associated delta-like protein 3 (DLL3)⁶, which is expressed in more than 80 percent of small cell lung cancer (SCLC) patient tumors, where it is prevalent on tumor cells, including cancer stem cells, but not present in healthy tissue.⁷ Rova-T combines a targeted antibody that delivers a cytotoxic agent directly to the DLL3-expressing cancer cells while minimizing toxicity to healthy cells. Rova-T is under investigation as a third-line treatment in SCLC.⁷ Studies designed to select a Rova-T regimen for first-line registration will be starting soon.⁸ The expression of DLL3 suggests Rova-T may be useful across multiple tumor types, including metastatic melanoma, glioblastoma multiforme and some prostate, pancreatic and colorectal cancers.⁷ 

Rova-T is an investigational compound and its efficacy and safety have not been established by the FDA or any other health authority.

About AbbVie
AbbVie is a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott Laboratories. The company's mission is to use its expertise, dedicated people and unique approach to innovation to develop and market advanced therapies that address some of the world's most complex and serious diseases. Together with its wholly-owned subsidiary, Pharmacyclics, AbbVie employs more than 28,000 people worldwide and markets medicines in more than 170 countries. For further information on the company and its people, portfolio and commitments, please visit www.abbvie.com. Follow @abbvie on Twitter or view careers on our Facebook or LinkedIn page.

About AbbVie in Oncology
AbbVie is striving to outsmart cancer by working with scientists, physicians, industry peers, patient advocacy groups and most importantly patients, to discover, develop and provide new therapies that will have a remarkable impact on the lives of people around the world affected by cancer. Our goal is to provide medicines that make a transformational improvement in cancer treatment and outcomes for cancer patients. By exploring and investing in new pathways, technologies and approaches, AbbVie is breaking ground in some of the most widespread and difficult-to-treat cancers.  We are also exploring solutions to help patients obtain access to our cancer medicines. With the acquisition of Pharmacyclics in 2015, and through several collaborations, AbbVie's oncology portfolio consists of marketed medicines and a pipeline containing multiple new molecules being evaluated worldwide in nearly two hundred clinical trials in 20 different tumor types. For more information about AbbVie Oncology, please visit www.abbvieoncology.com.    

Forward-Looking Statements
Some statements in this news release may be forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions, among others, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those indicated in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," in AbbVie's 2015 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission. AbbVie undertakes no obligation to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law.

References

¹ National Cancer Institute. General Information about Small Cell Lung Cancer (SCLC). Accessed June 2016. http://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq.

² Sant M, Allemani C, Santiaquilani M et al. EUROCARE-4. Survival of cancer patients diagnosed in 1995-1999. Results and commentary. Eur J Cancer 2009; 45: 931–991

³ American Cancer Society. Small cell lung cancer survival rates by stage. Accessed June 2016. www.cancer.org/cancer/lungcancer-smallcell/detailedguide/small-cell-lung-cancer-survival-rates.

⁴ Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray, F. GLOBOCAN 2012 v1.1, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2014. Accessed January 2015. http://globocan.iarc.fr.  

⁵ Fruh M, et al. Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of Oncology 2013; v24, supplement 6 https://annonc.oxfordjournals.org/content/24/suppl_6/vi99.full.pdf+html.

⁶ Saunders L. R. et al. A DLL3-targeted antibody-drug conjugate eradicates high-grade pulmonary neuroendocrine tumor-initiating cells in vivo. Sci. Transl. Med. 2015;7(302): 1-13.

⁷ ClinicalTrials.gov (2016). Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY). Accessed May 12, 2016. https://clinicaltrials.gov/ct2/show/NCT02674568?term=SC16LD6.5&rank=2.

⁸ ClinicalTrials.gov (2016). Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors. Accessed May 12, 2016. https://clinicaltrials.gov/ct2/show/NCT02709889?term=SC16LD6.5&rank=3#wrapper.

SOURCE AbbVie

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