
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. |