Cancer cells differ from one another based on what genes have mutations. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer growth driving abnormalities in a cancer’s genome that can be targeted with drugs and immunotherapies engineered to directly attack cancer cells with a specific genetic abnormality with the goal of leaving normal cells largely unharmed.
Antibody-drug-conjugates are one type of precision cancer medicines increasingly being used. ADCs work by delivering cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. The ADC ABBV-011 undergoing development appears promising for the treatment of small cell lung cancer (SCLC)
About Small Cell Lung Cancer
According to the American Cancer Society, more than 234,000 people will be diagnosed with lung cancer and over 160,00 will die from the disease every year making it the leading cause of cancer death. SCLC primarily is associated with smoking and accounts for about 10 to 15 percent of all lung cancers. The survival for most SCLC patients is less than a year and there have been few advances in its treatment.
About ABBV -011
ABBV-011 is a novel ADC directed at SEZ6, a transmembrane protein encoded by the SEZ6 gene located on chromosome 17 and is highly expressed in SCLC and other neuroendocrine tumors with minimal expression in most normal tissues. ABBV-011 is comprised of an anti-SEZ6 IgG1 monoclonal antibody, a non-cleavable linker, and a calicheamicin payload. Calicheamicin is the payload for two other precision medicines already approved for the treatment of cancer; Mylotarg (gemtuzumab ozogamicin), an anti-CD33 drug used for acute myeloid leukemia, and Besponsal (inotuzumab ozogamicin) an anti-CD22 drug used for acute lymphoblastic leukemia.1,2
According to findings from a first-in-human phase 1 trial presented at the 2023 ASCO Annual Meeting ABBV-011 was well tolerated and has promising activity against SCLC. ABBV-011 elicited a confirmed objective response rate of 19% when administered to individuals with advanced SCLC who had failed 1 to 3 prior treatment regimens. In 40 patients with SEZ6-positive SCLC the response rate was 25%.
Among 445 patients who were tested for SEZ6, 86% had SEZ6 expression on 1% or more tumor cells and 55% had expression on 25% or more tumor cells at targetable levels.
The most common side effects with ABBV-001 included fatigue, nausea , decreased appetite, a low platelet count, and constipation.
References
- Morgensztern D, Ready NE, Johnson ML, et al. First-in-human study of ABBV-011, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate, in patients with small cell lung cancer. J Clin Oncol. 2023;41(suppl 16):3002. doi:10.1200/JCO.2023.41_suppl.16.3002
- A study of ABBV-011 alone and in combination with budigalimab (ABBV-181) in participants with relapsed or refractory small cell lung cancer. ClinicalTrials.gov. Updated May 16, 2023. Accessed June 5, 2023. https://www.clinicaltrials.gov/ct2/show/NCT03639194
