Asco-GI 2022 – Seagen keeps the faith in souped-up CD40 agonism

Do not write off CD40. Stimulating this target for oncology use has proved difficult, but companies are not giving up, though many have accepted that something more than a simple agonist approach might be needed. Seagen’s SEA-CD40 is a nonfucosylated CD40 agonist MAb, and phase 1 data just unveiled at the Asco-GI meeting show 44% overall response across two doses in 61 evaluable patients in a first-line pancreatic ductal adenocarcinoma cohort; median PFS and OS are 7.4 and 15.0 months respectively. It is difficult to parse SEA-CD40’s contribution, as the project was combined with Keytruda, Abraxane and gemcitabine, but Abraxane’s label cites ORR, mPFS and mOS of 23%, 5.5 months and 8.5 months, respectively, in combination with gemcitabine. SEA-CD40 recently moved into phase 2, as did Celldex’s fully human agonist CDX-1140, while new clinical entrants since Evaluate Vantage last analysed the CD40 field include Abbvie’s ABBV-927, Biontech/Genmab's GEN1042, Lyvgen’s LVGN7409 and Shattuck’s SL-172154. Discontinuations include ABBV-428 and Astrazeneca’s MEDI5083, while Roche recently canned selicrelumab in favour of RG6189, a bispecific that induces CD40 stimulation solely in the presence of FAPα and is now in a phase 1 Tecentriq combo trial.

Selected clinical assets targeting CD40 in cancer
Project Company Mechanism Clinical trial
Phase 2
APX005M/ sotigalimab Apexigen CD40 agonist MAb Melanoma and oesophageal/GEJ
CDX-1140 Celldex Therapeutics Fully human CD40 agonist MAb Pancreatic cancer
SEA-CD40 Seagen Nonfucosylated CD40 agonist MAb Combo trial
ABBV-927 Abbvie CD40 agonist MAb Pancreatic cancer
YH003 Eucure (Biocytogen) Humanised CD40 agonist MAb Toripalimab combo
Phase 1/2
Mitazalimab/ ADC-1013 Alligator Bioscience CD40 agonist MAb; J&J terminated deal Jul 2019 Pancreatic cancer
GEN1042 Biontech/Genmab CD40 & 4-1BB Duobody Solid tumours
Phase 1
FAP-CD40/ RO7300490 Roche FAPα-dependent CD40 agonist bispecific  Tecentriq combo
LVGN7409 Lyvgen Biopharma CD40 agonist MAb MonoRx & combo
SL-172154 Shattuck Labs CD40L-SIRPα fusion protein Ovarian and head & neck cancers
Source: Evaluate Pharma. Note: excludes non-oncology applications and CD40-blocking approaches for autoimmune diseases.

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