7:43 PM
May 31, 2019
 |  BioCentury  |  Product Development

ASCO 2019 abstracts show solid tumor race heating up among bispecifics and CAR Ts

BioCentury’s analysis of ASCO 2019 abstracts shows bispecifics outpacing CAR Ts in solid tumors

While strong progress in CAR T therapies will again feature at this year’s ASCO meeting, bispecific antibodies are having a moment -- making more inroads into solid tumors than CAR Ts and branching out via new strategies.

BioCentury’s fourth annual survey of abstracts at the American Society of Clinical Oncology (ASCO) meeting presents a snapshot of clinical research in cancer, according to a machine learning-based analysis of 4,627 abstracts for mentions of products, indications, targets, modalities or other hot topic terms.

The 2019 analysis documents 31 novel targets and 22 products in first-in-human trials presented at the meeting, as well as trends in two technologies to improve clinical trials and regulatory decisions (see Table: “ASCO 2019 New Targets” and “Clinical Trial and Regulatory Efficiency Get Help from ctDNA, RWE at ASCO19”).

The 2019 analysis documents 31 novel targets and 22 products in first-in-human trials presented at the meeting.

New modalities continue to advance, with nine of the first-in-human products outside of traditional small molecule and antibody modalities (see Table: “ASCO 2019 First-in-Human Abstracts”).

Bispecific antibodies threaten to steal the show. Though the total number of abstracts mentioning bispecifics -- including one tetraspecific compound -- is still less than some other new modalities, the class showed a substantial surge in activity this year over last (see Figure: “ASCO 2019 Modalities”).

Figure: ASCO 2019 modalities

New modalities continue to be well represented at this year’s American Society of Clinical Oncology (ASCO) meeting. Though bispecific antibodies rank sixth for the number of mentions in abstracts, the class saw the biggest rise over 2018 among the new modalities, followed by CAR T cell therapies. Top graph shows the number of abstracts in 2019; bottom graph shows percent change from 2018. While the number of ADC abstracts fell this year, four products will have first-in-human data presented.

Modalities were identified using a machine learning-based text search of abstracts assigned to any of ASCO’s presentation tracks related to clinical, preclinical or basic research. Exosomes and liposomes were categorized as nanoparticles, and include liposomal chemotherapy formulations. The vaccine category includes DNA, neoantigen, peptide and RNA vaccines. The nucleic acid category includes antisense oligonucleotides, siRNA, shRNA, microRNA (miRNA), long noncoding RNA (lncRNA) and small activating RNA (saRNA). The bispecific category contains one abstract describing tetraspecific antibodies. The other cell therapy category includes all cell therapies minus CAR T cells. mAbs and small molecules were excluded from this analysis. The analysis also excluded abstracts assigned to tracks related to survivorship, supportive care and symptom management. Source: ASCO abstracts as of May 15

CAR T cell therapies saw the second biggest increase. The dominance of bispecifics indicates a resurgence of activity for a modality that has been largely eclipsed by CAR Ts, in particular since Novartis AG’s Kymriah tisagenlecleucel became the first FDA-approved CAR T in 2017.

The first bispecific antibody to receive FDA approval was Amgen Inc.’s Blincyto blinatumomab, in 2014, but the modality has been dogged by stability and toxicity issues.

Despite the headstart for bispecifics, both modalities have two products on the market, and all four are approved for liquid tumors.

Last year’s American Society of Hematology (ASH) meeting suggested the bispecific dam may finally be breaking, at least in blood cancers (see “Intermittent Move Beyond Blincyto”).

The next step for both modalities is achieving efficacy in solid tumors, and the ASCO abstracts suggest bispecifics could take the lead, as they are covering more targets and being tested in a wider range of solid tumor indications.

Table: ASCO 2019 first-in-human abstracts

The first efficacy data from at least 22 first-in-human trials are being presented at this year’s American Society of Clinical Oncology meeting in Chicago. The therapies span 21 targets and seven modalities.

Although the total number of abstracts mentioning ADCs fell this year compared with 2018, the modality appears to be advancing, with companies presenting first-in-human data from four candidates. The list includes HuMax-AXL-ADC from Genmab A/S (CSE:GEN;Pink:GMXAY) and Seattle Genetics Inc. (NASDAQ:SGEN), and ABBV-085 from AbbVie Inc. (NYSE:ABBV). Both therapies are in development for sarcoma, among other solid tumor types. According to BioCentury’s BCIQ database, only one other ADC is in the clinic for sarcoma.

For bispecific antibodies and CAR T cell therapies, solid tumors are the next frontier, and both modalities are represented in first-in-human solid tumor abstracts. These include bispecifics pasotuxizumab from Amgen Inc. (NASDAQ:AMGN) and partner Bayer AG (Xetra:BAYN), KN046 from Suzhou Alphamab Co. Ltd. spinout Alphamab Oncology Ltd., and a mesothelin-targeted CAR T therapy from Memorial Sloan Kettering Cancer Center.

Miltenyi Biotec GmbH and collaborators will present first-in-human data from a CAR T to treat non-Hodgkin lymphoma (NHL).

Multiple small molecules on the list are designed to inhibit historically difficult targets. For example, Amgen Inc. will present the first data from AMG 510, an inhibitor that selectively targets the G12C...

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