Coverage by Allison Inserro, Laura Joszt, Samantha DiGrande, Jaime Rosenberg, Mary Caffrey, and David Bai, PharmD
Amgen AMG 420 Finds Early Success in Patients With Relapsed and Refractory Multiple Myeloma
AMG 420, a bispecific T-cell engager (BiTE) from Amgen for the treatment of patients with relapsed and refractory multiple myeloma (RRMM), has found positive preliminary results in a phase 1 trial. The development of AMG 420 adds another contender to the immunotherapy category for treating MM.
In 2016, Amgen bought the BiTE platform from Boehringer Ingelheim.1 BiTE combats cancer by directing T cells to destroy cancer cells. It consists of 2 single chain antibodies: one specific for B-cell maturation antigen (BCMA), a tumor antigen, and the other specific for CD3, a protein on the surface of T cells. By binding to BCMA and CD3, BiTE technology forms a bridge between the T cell and the tumor cell. This lets the T cell target the tumor cell, resulting in tumor cell lysis and reduced tumor burden and therefore halting the progression of the cancer.1-3
By 2018, AMG 420, an anti-BCMA BiTE product, was considered potentially beneficial in patients with RRMM. Preliminary results were reviewed, and findings showed that 5 patients on AMG 420 were able to obtain stringent complete responses, with 4 of the patients having negative minimal residual disease exceeding 10 months.2 AMG 420 is still in phase 1 trials, but the positive results may streamline AMG 420 ahead into future clinical trials.
Another drug that has entered the MM drug development market is bb2121, an anti-BCMA chimeric antigen receptor (CAR) T drug developed by Celgene with bluebird bio, Inc, also designed to treat patients with RRMM. Although it was created to target the same population as AMG 420, bb2121 is a gene therapy. T cells extracted from the white blood cells of a patient are collected and genetically modified to recognize BCMA. They are then returned to the body of the patient, so they can target MM tumor cells that express the BCMA.4
Results from phase 1 study of bb2121 were revealed at the annual meeting of the American Society of Clinical Oncology in June. The overall response rate in the 18 patients with RRMM was 94%, with 56% (10 patients) having complete response. Nine of the 10 patients were also MRD-negative. At 40 weeks, the median duration of response and progression-free survival were not reached.5Currently, bb2121 is in phase 2 and 3 trials, for which Celgene and bluebird bio, Inc, had begun testing the efficacy and safety of bb2121 and comparing it with other treatment options for MM (NCT03361748, NCT0365112).
Right now, there is reason to believe that AMG 420 may have similar efficacy to bb2121 for treating patients with RRMM. But this assumption will not be verified until the results of longer-term data are available. The development of these new drugs in the field of MM is groundbreaking, and it will be very interesting to see where these drugs will fit within MM treatment guidelines.
2. Chrisomalis T. Amgen looks to enter multiple myeloma space: can it compete? Seeking Alpha website. seekingalpha.com/article/4205437-amgen-looks-enter-multiple-myeloma-space-can-compete. Updated September 10, 2018. Accessed September 19, 2018.
3. Amgen Oncology. BiTE: engage the immune system. biteantibodies.com. Accessed September 19, 2018.
4. Bb2121. Immuno-Oncology News website. immuno-oncologynews.com/bb2121. Accessed September 19, 2018.
5. Raje NS, Berdeja JG, Lin Y, et al. bb2121 anti-BCMA CAR T-cell therapy in patients with relapsed/refractory multiple myeloma: updated results from a multicenter phase 1 study. Presented at: the 2018 Annual Meeting of the American Society of Clinical Oncology; June 1, 2018; Chicago, IL. Abstract 8007. abstracts.asco.org/214/ AbstView_214_211179.html.
FDA Accepts First Allogeneic CAR T-Cell Therapy Trial
Celyad, a biopharmaceutical company that focuses on the development of chimeric antigen receptor (CAR) T-cell therapies, recently announced1 that the FDA accepted its investigational new drug (IND) application for CYAD-101, the first non–gene-edited allogeneic clinical program.
Traditionally, CAR T-cell therapies are created by genetically modifying a patient’s immune cells to target specific cancer cells before injecting them back into the patient. However, this can be difficult because researchers aren’t always able to collect enough cells from a patient to create the treatment. Conversely, in an allogeneic CAR T-cell therapy, immune cells are collected from healthy donors, rather than the patient.
The Allo-SHRINK trial looks to evaluate the safety and clinical activity of CYAD-101 in patients with unresectable colorectal cancer in combination with standard chemotherapy. “We are pleased to have achieved this im- portant milestone. Celyad is the first company clinically evaluating a non– gene-edited CAR T candidate, which, we believe, offers significant advantages over gene-edited approaches,” Christian Homsy, MD, CEO of Celyad, said in a statement.
CYAD-101 is based on features of the company’s investigational autologous CYAD-01 CAR T with a novel peptide, TCR Inhibiting Molecule (TIM). This prevents the patients’ immune system from recognizing the cells as foreign. The cells in CYAD-01 produce a chimeric receptor, called natural killer group 2D (NKG2D), that recognizes multiple tumor proteins.
Celyad’s investigational autologous CYAD-01 treatment is currently being tested in 3 phase 1 trials for different cancers, including SHRINK,2 which is investigating increasing doses of CYAD-01 with chemotherapy in patients with colorectal cancer whose liver metastasis can be removed by surgery; LINK,3 which is examining increasing doses of CYAD-01 in patients with colorectal cancer with liver metastases that cannot be removed by surgery; and THINK,4 which is evaluating CYAD-01 in 7 types of refractory cancers, including 5 solid tumors.
“Our non–gene-edited program consists of a family of technologies aimed at reducing or eliminating T-cell receptor (TCR) signaling without requiring genetic manipulation. CYAD-101 is part of a robust clinical development plan, establishing the foundations of next-generation CAR T products,” said Homsy.
1. Celyad announces FDA acceptance of IND application for CYAD-101, a first-in-class non-gene edited allo- geneic CAR T candidate [press release]. Mont-Saint-Guibert, Belgium: Celyad; July 24, 2018. globenewswire.com/news-release/2018/07/24/1540949/0/en/Celyad-Announces-FDA-Acceptance-of-IND-Application-for-CYAD-101-a-First-in-Class-Non-Gene-Edited-Allogeneic-CAR-T-Candidate.html. Accessed August 4, 2018.
2. Dose Escalation and Dose Expansion Phase 1 Study to Assess the Safety and Clinical Activity of Multiple Doses of NKR-2 Administered Concurrently With FOLFOX in Colorectal Cancer With Potentially Resectable Liver Metastases (SHRINK). clinicaltrials.gov/ct2/show/NCT03310008. Updated June 1, 2018. Accessed August 4, 2018.
3. Hepatic Transarterial Administrations of NKR-2 in Patients With Unresectable Liver Metastases From Colorectal Cancer (LINK). clinicaltrials.gov/ct2/show/NCT03370198. Updated June 1, 2018. Accessed August 4, 2018.
4. A Dose Escalation Phase 1 Study to Assess the Safety and Clinical Activity of Multiple Cancer Indications (THINK). clinicaltrials.gov/ct2/show/NCT03018405. Updated January 18, 2018. Accessed August 4, 2018.
Cancer Screening Rates in the US Fall Short of Healthy People 2020 Targets
With Healthy People 2020 goals of achieving health equity, eliminating disparities, and improving the health of all groups, cancer screening plays an integral role in achieving these goals. However, cancer screening rates in the United States fall short of these targets and significant disparities exist among subgroups, according to CDC data.1
The agency’s research focused on breast, cervical, colorectal, and prostate cancers, as these accounted for nearly 40% of new cancer diagnoses and close to 20% of cancer deaths in 2013. Among the goals of Healthy People 2020 are increasing the proportion of women aged 21 to 65 years screened for cervical cancer, women aged 50 to 74 years screened for breast cancer, and men and women aged 50 to 75 years screened for colorectal cancer. Their goals also include reducing prostate cancer deaths.
Using the National Health Interview Study, researchers collected data from participants on Papanicolaou (Pap) tests, hysterectomies, mammograms, pros- tate-specific antigen (PSA) tests, and endoscopic exams and fecal occult blood tests (FOBTs) screening for colorectal cancer. Women were considered to have been screened recently for breast cancer if they had a mammogram within 2 years and screened for cervical cancer if they had a Pap test within 3 years.
Having an FOBT within the past year, a flexible sigmoidoscopy within 5 years and an FOBT within 3 years, or a colonoscopy within 10 years signified a recent colorectal cancer screening. The authors noted that at the time of analysis, the US Preventive Services Task Force (USPSTF) was following its 2012 guideline that recommended against routine PSA screening.
Of the 83% of women who received a recent Pap test, women aged 21 to 30 and women aged 51 to 60 years were less likely to have been screened. More than two-thirds (71.7%) also reported having a recent mammogram. Similar to Pap testing, mammography testing was least likely among those aged 50 to 64 years. Although screening rates were high, they fell short of the Healthy People 2020 targets of 93% for Pap tests and 81% for mammography. For colorectal screening, 63.4% of women and 61.9% of men reported having a recent screening, falling below the target of 80%. Across the 3 screening methods, having less than a high school education, having no usual source of care, having public insurance, and being underinsured were associated with lower testing rates.
Among men, 35.8% reported having a recent PSA test in the past year.
Between 2000 and 2015, Pap test use declined by 4.3% among women with a usual source of care and mammography rates declined by 3%. Only use of colorectal cancer screening has increased significantly and consistently, rising 25.1% among women between 2000 and 2010. Rates stayed stable between 2010 and 2013 and then increased slightly in 2015. Colorectal cancer screening among men also increased significantly.
Use of a PSA test declined by 9.2% from 2008 to 2013 but remained stable between 2013 and 2015. The authors noted that this drop can be attributed to USPSTF’s recommendation against routine screening and, subsequently, a drop in the test being offered by physicians and used by patients. Earlier this year, USPSTF updated their recommendation,2 calling for men aged 55 to 69 years to make their own decision on whether to be screened periodically for prostate cancer after they have had a conversation with their physician on potential benefits and harms.
“One approach to improving screening use across all subgroups would be for physicians to recommend screening to all age-appropriate patients, including traditionally underserved groups,” they wrote. They add that physician enthusiasm and outreach with tailored or innovative strategies to educate and inform may increase knowledge and intention to screen among these underserved groups.
1. CDC. Patterns and trends in cancer screening in the United States. CDC website. cdc.gov/pcd/issues/2018/17_0465.htm. Published July 26, 2018. Accessed July 31, 2018.
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