Takeda | TAK-788 (EGFR Exon 20 insertion inhibitor)| Phase 1/2: Pivotal trial results

EGFR Exon 20 NSCLC - October 2020

18 Sep 2020

Mobocertinib (TAK-788, AP32788; Selective EGFR and HER2 exon 20 insertion mutation tyrosine kinase inhibitor) – Takeda

Takeda presented the updated results of TAK-788 from Phase 1/2 EXCLAIM trial at ESMO2020
Results: As of Jan 27, 2020, 28 pts dosed with TAK-788 at 160 mg QD. Out of which, 26 patients were evaluable
- Efficacy:
  Parameter
  Result
  Objective response rate (ORR)
  43%
  Median duration of response (mDOR)
  13.9 months
  Disease control rate (DCR)
  86%
  Median progression free survival (mPFS)
  7.2 months
  Progressive disease (PD)
  2 pts
- Safety:
  - Most common TEAEs any grade (>25%): diarrhea (82%), rash (46%), nausea (39%), decreased appetite (39%), vomiting (36%), paronychia (29%)
  - Grade ≥3 TRAEs (≥5%): diarrhea (32%), nausea (11%), increased lipase (7%), increased amylase (7%), stomatitis (7%), vomiting (7%) among 28 patients
  - Most common TEAEs (≥1 dose of 160 mg): diarrhea (83%), nausea (43%), rash (33%), vomiting (27%)
  - Grade ≥3 TRAEs (≥1 dose of 160 mg): diarrhea (21%) and increased lipase (5%)
  - Safety profile was consistent with other EGFR TKIs

CI Scientists Remarks:

Mobocertinib is a potent, small-molecule TKI. It is specifically designed to selectively target EGFR and human EGFR2 (HER2) Exon20 insertion mutations
Interim data published at ESMO2020 is from the pivotal Phase 2 EXCLAIM trial evaluating 306 patients in 2L+ mNSCLC with EGFR exon 20 mutation. It is a non-randomized, open-label, multi-centered trial; PCD: May 29, 2020

The molecule is also being evaluated as 1L therapy in Phase 3 pivotal trial

Pivotal trial	Condition	Data readout	Estimated NDA filing in US	Estimated approval
EXCLAIM	2L+; locally advanced mNSCLC with EGFR exon 20 mutation	FY’20	H2 FY’20	FY’21
EXCLAIM-2	1L; locally advanced, recurrent or mNSCLC with EGFR exon 20 mutation	FY’22	NA	FY’23

FDA granted ODD to mobocertinib for the treatment of NSCLC with HER2 or EGFR mutations including Exon 20 insertion mutations and BTD for patients with EGFR Exon 20 insertion mutation mNSCLC, whose disease has progressed on or after platinum-based chemotherapy

– Dr. Rakshith, CI Scientists

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Parameter	Result
Objective response rate (ORR)	43%
Median duration of response (mDOR)	13.9 months
Disease control rate (DCR)	86%
Median progression free survival (mPFS)	7.2 months
Progressive disease (PD)	2 pts