dm+d

Unassigned

New Medicines

Non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation - second-line

Information

New molecular entity
Takeda
Takeda

Development and Regulatory status

Phase II Clinical Trials
Pre-registration (Filed)
Pre-registration (Filed)
Jul 21Filed in EU [7].
Apr 21US FDA granted priority review with a Prescription Drug User Fee Act (PDUFA) action date for 26th October 2021 based on positive PI/II data.[6]
Apr 21US FDA granted Breakthrough Therapy Designation for mobocertinib (TAK-788) for metastatic NSCLC with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.[6]
Apr 21US FDA accept NDA for Priority Review [5].
Feb 20Takeda anticipates approvals in financial year 21/22 [3].

Category

First-in-class tyrosine kinase inhibitor of activating exon 20 mutations in EGFR and HER2
There were 46,403 new cases of lung cancer diagnosed in the UK in 2014. NSCLC accounts for 85% of cases of lung cancer. The NSCLCs are often grouped together when treatment is being considered [1].
Non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutation - second-line
Oral

Further information

Yes

Trial or other data

May 21PI/II EXCLAIM study is still recruiting [4].
Jan 21New data from the Phase 1/2 trial (n=114) shows a confirmed objective response rate (ORR) of 35% per investigator and 28% compared to an independent review committee. Median progression-free survival was 7.3 months with a median duration of response of 17.5 months. The disease control rate was 78%. The most common treatment-related adverse events (≥ 20%) in platinum-pretreated pts were diarrhoea (90%), rash (45%), paronychia (34%), nausea (32%), decreased appetite (32%), dry skin (30%) and vomiting (30%) and 19 discontinued due to side effects. [5]
Jun 16PI/II EXCLAIM study to evaluate the safety, pharmacokinetics, and anti-tumor activity of oral EGFR/HER2 Inhibitor TAK-788 in participants with NSCLC and anti-tumor activity of TAK-788 in participants with solid tumors other than NSCLC with EGFR or HER2 mutations starts (NCT02716116). The trial will be conducted in three parts: a dose escalation (Part 1), including Part 1A (dose escalation combination component of TAK-788 in combination with Pemetrexed/Carboplatin) and Part 1B (TAK-788 monotherapy and TAK-788 in combination with pemetrexed/carboplatin with primary antidiarrhea prevention with loperamide.) and expansion phase (Part 2), followed by an extension phase (Part 3). The objectives of the dose escalation phase (Part 1),dose escalation combination phase (Part 1A, only for selected sites in the United States) and Antidiarrhea Prophylaxis Cohorts ( part 1B, only for selected sites in the United States) are to determine the safety profile of orally administered TAK-788 and TAK-788 in combination with Pemetrexed/Carboplatin, including the MTD, DLTs, RP2D,pharmacokinetic profile and with loperamide as primary antidiarrhea prevention incidence and severity of TAK-788-associated diarrhea and anti-tumor activity of TAK-788 (Part 1B) . The primary goal of the expansion component of the trial is to evaluate the anti-tumor activity of TAK-788 in seven histologically and molecularly defined cohorts at the RP2D (determined based on dose escalation phase of the trial). 395 adults will be recruited in the UK, US, EU and other countries. Collection of primary outcome data due to complete Mar 22 [2]

Advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutation - first-line

Information

Licence extension / variation
Takeda
Takeda

Development and Regulatory status

None
Phase III Clinical Trials
Phase III Clinical Trials

Category

First-in-class tyrosine kinase inhibitor of activating exon 20 mutations in EGFR and HER2
There were 46,403 new cases of lung cancer diagnosed in the UK in 2014. NSCLC accounts for 85% of cases of lung cancer. The NSCLCs are often grouped together when treatment is being considered [1].
Advanced or metastatic non-small cell lung cancer (NSCLC) harboring EGFR exon 20 insertion mutation - first-line
Oral

Evidence based evaluations