The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

AIRR Community and Tsinghua University discuss Chinese research using AIRR-seq data to study adaptive immune response in COVID-19 patients

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A meeting focusing on Chinese researchers’ use of AIRR-seq data to study the adaptive immune response – especially in COVID-19 patients – was held recently by the AIRR Community and Tsinghua University.

The purpose of this co-organized meeting was to expose AIRR-seq researchers in China to the philosophy and tools developed by the AIRR Community and help integrate researchers from all over the world through the AIRR Community.

Although collaboration and sharing data internationally is complicated and difficult, this successful meeting was an important step in forming the relationships necessary for overcoming many of these challenges.

Tsinghua University is a major research university in Beijing and a member of the C9 League of Chinese universities. Since its establishment exactly 110 years ago, it has produced many notable leaders in science, engineering, politics, business, academia, and culture. The university is ranked as the 15th best university in the world in the QS World University Rankings and No.1 in Asia by the Asia University Rankings and the U.S. News and World Report.

The meeting followed a hybrid format, combining online lectures by AIRR Community members in the US and Europe in conjunction with an in-person meeting in Shenzhen, China that was organized by Professor Xiao Liu of Tsinghua University’s Shenzhen campus.

The in-person, all-day meeting was held on December 6, 2020 in Shenzhen, which corresponded to Saturday evening December 5 in North America.

The full meeting agenda can be found on the meeting web page and the meeting recording has been posted on the AIRR-C YouTube Channel.

 

Congratulations to the Antibody Engineering & Therapeutics Europe poster competition winners!

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To recognize the research activities of promising student/postdoctoral fellows, The Antibody Society sponsors a competition each year for members who submit posters for Antibody Engineering & Therapeutics Europe. This conference will be held virtually June 8-10, 2021.
Our judges select the best work based on originality, relevance and perceived impact on the field of antibody research and development.

 

Winners receive:

1) Complimentary registration to attend the conference and pre-conference sessions;
2) An opportunity to give a short oral presentation of their work in one of the conference sessions;
3) A lovely crystal award.

We are pleased to announce the winners of the 2021 poster competition:

Ms. Suchada Niamsuphap, Australian Institute for Bioengineering and Nanotechnology.

Poster title: Development of antibody delivery systems against intracellular targets

and

Dr. Vaishali Verma, University of Delhi South Campus.

Poster title: ImPACT: Immunization-free Phage-based Antibody Cloning Technology

More about these winners and the winners of past competitions can be found here.

Please join us for the virtual Antibody Engineering & Therapeutics Europe conference on June 8-10 to hear their presentations!

Society members receive a 15% discount on the registration fee. Contact us at membership@antibodysociety.org for the code.

Antibody therapeutics for melanoma

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May is Melanoma Awareness Month, with awareness campaigns kicking off on the first Monday (May 3rd in 2021). Melanoma is caused by cancerous melanocytes, which are cells in the epidermis that normally make a pigment, melanin, that protects other skin cells from damaging sun rays. The American Cancer Society (ACS) estimates the lifetime risk for developing the disease is ~ 2.6% (1 in 38) for whites, and 0.6% (1 in 167) for Hispanics, and 0.1% (1 in 1,000) for Blacks. Overall, melanoma is more common in men, and the risk of melanoma increases with age. The ACS’ data suggest that ~ 106,110 new melanomas will be diagnosed (~62,260 in men and 43,850 in women) and ~ 7,180 people may die of the disease in the United States during 2021.

Approved antibody therapies for melanoma

Three antibody therapeutics (ipilimumab, nivolumab, pembrolizumab)  that target the immune checkpoints CTLA-4 (CD152) or programmed cell death protein 1 (PD-1, CD279) are approved for melanoma.

  • YERVOY (ipilimumab), which targets cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), is indicated for the treatment of unresectable metastatic melanoma in adults and pediatric patients (12 years and older) and adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection, including total lymphadenectomy.
  • KEYTRUDA (pembrolizumab), which targets PD-1, is indicated for the treatment of patients with unresectable or metastatic melanoma, and for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.
  • OPDIVO (nivolumab), which targets PD-1, is indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression, including following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor, and for the adjuvant treatment of patients with melanoma with involvement of lymph node(s) following complete resection.

Combination therapy was shown to be superior to monotherapy with these checkpoint inhibitors in the Phase 3 Checkpoint study, which evaluated nivolumab monotherapy or nivolumab combined with ipilimumab versus ipilimumab monotherapy in patients with previously untreated unresectable or metastatic melanoma. The overall survival (OS) at 5 years was 52%, 44% and 26% in the nivolumab-plus-ipilimumab, nivolumab monotherapy, and ipilimumab monotherapy groups, respectively. However, Grade 3 or 4 treatment-related adverse events occurred more frequently in patients who received combination therapy (59%, 23%, and 28% of patients in the nivolumab-plus-ipilimumab, nivolumab, and ipilimumab treatment groups, respectively).

Investigational antibody therapies for melanoma

While the antibody therapeutics that target CTLA-4 and PD-1 have benefited melanoma patients, biopharmaceutical companies are developing novel antibody therapeutics that target other immune checkpoints such as LAG-3 or use different mechanisms of action.

  • Bristol-Myers Squibb is developing relatlimab (BMS-986016), which is a human IgG4 antibody targeting LAG-3 on T cells, thereby restoring effector function of exhausted T cells. Primary results from the Phase 2/3 RELATIVITY-047 (CA224-047) trial evaluating the fixed-dose combination of relatlimab and Opdivo (nivolumab) versus Opdivo alone in patients with previously untreated metastatic or unresectable melanoma indicated that the trial met its primary endpoint of progression-free survival.
  • Philogen  S.p.A. is developing Nidlegy, which is composed of two single-chain variable fragment (scFv)-based immunocytokines that target extra-domain B of fibronectin (L19IL2 + L19TNF combination), as neoadjuvant intralesional treatment for melanoma patients with locoregional disease. Two randomized, controlled Phase 3 registration trials for intralesional application of Nidlegy as a neoadjuvant followed by surgery + eventual adjuvant treatments (standard of care) and compared to standard of care are currently ongoing in Europe (PIVOTAL; NCT02938299) and in the USA (Neo-DREAM; NCT03567889) in patients with fully resectable stage IIIB/C melanoma.
  • Immunocore Ltd is developing tebentafusp, which comprises a high- affinity T cell receptor specific to a peptide sequence from the gp100 antigen, which is presented on melanoma tumor cells by HLA-A2, fused to an anti-CD3 single chain antibody fragment. In a Phase 3 study, tebentafusp demonstrated a statistically significant and clinically meaningful improvement in OS as a first-line treatment in metastatic uveal melanoma.  Tebentafusp has been granted Breakthrough Therapy Designation, Fast Track designation and orphan drug designation by the FDA and Promising Innovative Medicine designation under the UK Early Access to Medicines Scheme for metastatic uveal melanoma. Immunocore will be working with the FDA to complete submission of a BLA for tebentafusp in the third quarter of 2021.

The Antibody Society continuously collects data for antibody therapeutics in the commercial clinical pipeline. We will provide updates on the antibody therapeutics being evaluated for melanoma in future posts.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Loncastuximab tesirine granted first approval by FDA for large B-cell lymphoma

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On April 23, 2021, the  US Food and Drug Administration (FDA) granted accelerated approval to loncastuximab tesirine-lpyl (Zynlonta, ADC Therapeutics SA) for adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, DLBCL arising from low grade lymphoma, and high-grade B-cell lymphoma. This marketing application was granted priority review and orphan drug designation by FDA. The review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.

Loncastuximab tesirine (ADCT-042) is an antibody-drug conjugate composed of an anti-CD19 humanized IgG1k antibody conjugated via a linker to pyrrolobenzodiazepine-dimer toxin that induces the killing of CD19-expressing malignant B cells.

The BLA submission was supported by data from the open-label, single-arm Phase 2 LOTIS 2 study (NCT03589469), which evaluated the safety and efficacy of loncastuximab tesirine for the treatment of patients with relapsed or refractory DLBCL following ≥2 lines of prior systemic therapy. A total of 145 patients received loncastuximab tesirine as an intravenous infusion over 30 minutes on Day 1 of each cycle (every 3 weeks) at a dose of 150 μg/kg for 2 cycles, then 75 μg/kg for subsequent cycles for up to one year or until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary outcome measure is the overall response rate (ORR). Positive initial data from LOTIS 2 were presented during the virtual 25th Annual Congress of the European Hematology Association. The ORR was 48.3% (70/145 patients), the complete response rate was 24.1% (35/145 patients), and the median duration of response was 10.25 months. The toxicity profile was manageable and no new safety concerns were identified.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Dostarlimab approved by FDA for endometrial cancer

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On April 22, 2021, the U.S. Food and Drug Administration (FDA) granted accelerated approval to Jemperli (dostarlimab) for treating patients with recurrent or advanced endometrial cancer that has progressed on or following prior treatment with a platinum-containing chemotherapy and whose cancers are deficient in their ability to repair DNA inside the cell, as determined by an FDA-approved test. FDA granted dostarlimab Priority Review and Breakthrough Therapy designations for this indication. Dostarlimab (TS-042, GSK4057190A) is an anti-PD-1 humanized IgG4k antibody generated by Anaptysbio under partnership with Tesaro, which was acquired by GlaxoSmithKline in 2019.

Interim analyses of data for patients with mismatch repair (MMR)-deficient endometrial cancer with recurrent or advanced disease that progressed on a platinum doublet regimen enrolled in the Phase 1 GARNET study (NCT02715284) were reported at the European Society for Medical Oncology (ESMO) Virtual Congress in September 2020. Patients received 500 mg of dostarlimab every 3 weeks for the first 4 cycles, then 1,000 mg every 6 weeks until disease progression or discontinuation. The primary endpoints included confirmed objective response rate (ORR) and duration of response (DOR). The ORR was 44.7% in patients with deficient mismatch repair (dMMR) disease and 13.4% in those with MMR-proficient (MMRp) disease. In the dMMR cohort (n = 103), 11 complete responses, and 35 partial responses were observed. Thirteen patients achieved stable disease, while 39 patients experienced disease progression. In the MMRp cohort (n = 142), 3 patients had complete responses, 16 had partial responses, 31 achieved stable disease, and 77 patients experienced progressive disease. At the time of data cutoff, with a median follow up of 11.2 months, the median DOR had not been reached.

Dostarlimab is also being evaluated as a treatment for various types of cancer in early-stage clinical studies, as well as two Phase 3 studies, RUBY and FIRST. The RUBY study (NCT03981796) is evaluating dostarlimab plus carboplatin-paclitaxel versus placebo plus carboplatin-paclitaxel in patients with recurrent or primary advanced endometrial cancer. The primary outcome measure is the progression-free survival (PFS) assessed by an investigator, and the primary completion date is July 2021. The FIRST study (NCT03602859) is a comparison of platinum-based therapy with dostarlimab and niraparib versus standard of care platinum-based therapy as first-line treatment of Stage III or IV non-mucinous epithelial ovarian cancer. The primary outcome measure is the PFS and the primary completion date is January 2023.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.