Takeda (TSE:4502/NYSE:TAK) today announced that EXKIVITY® (mobocertinib) has been approved by the National Medical Products Administration (NMPA) of China for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) Exon20 insertion mutations, whose disease has progressed on or after platinum-based chemotherapy.

Takeda’s oral drug Exkivity (mobocertinib) won the regulatory nod to treat non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion (Ex20ins) mutation in Korea.

EXKIVITY is a kinase inhibitor indicated for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy...This indication is approved under accelerated approval based on overall response rate and duration of response.

The UK's National Institute for Health and Care Excellence on Wednesday recommended approval of Takeda's Exkivity (mobocertinib) for patients with advanced non-small cell lung cancer harboring EGFR exon 20 insertion mutations.

Mobocertinib added as a subsequent therapy option for patients (PS 0-2) with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, whose disease has progressed on or after initial systemic therapy options (NSCL-K 1 of 5, NSCL-K 2 of 5). This is a category 2A recommendation.

The National Health Service England on Friday said it will fast track the availability of Takeda's Exkivity (mobocertinib) for metastatic non-small cell lung cancer patients who have EGFR exon 20 insertion mutations in their tumors and have already received chemotherapy.

Takeda Pharmaceutical Company Limited...today announced that that the U.S. Food and Drug Administration (FDA) has granted priority review for the company’s New Drug Application (NDA) for mobocertinib (TAK-788) for the treatment of adult patients with epidermal growth factor receptor (EGFR) Exon20 insertion mutation-positive (insertion+) metastatic non-small cell lung cancer (mNSCLC), as detected by an FDA-approved test, who have received prior platinum-based chemotherapy.

Takeda Pharmaceutical Company Limited...today announced that the U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation for its investigational drug mobocertinib (TAK-788) for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy.

...Have a documented EGFR in-frame exon 20 insertion by a local test....

...- Documented epidermal growth factor receptor (EGFR) in-frame exon 20 insertion mutation assessed by a clinical laboratory improvements amendment (CLIA)-certified (US sites) or an accredited (outside of the US) local laboratory The EGFR exon 20 insertion mutation can be either alone or in combination with other EGFR or human epidermal growth factor receptor 2 (HER2) mutations except EGFR mutations for which there are approved anti-EGFR tyrosine kinase inhibitors [TKIs] (ie, exon 19 del, L858R, T790M, L861Q, G719X, or S768I, where X is any other amino acid)...

...A documented epidermal growth factor receptor (EGFR) mutation with in-frame exon 20 insertion, confirmed as follows:...

...A documented EGFR in-frame exon 20 insertion (including A763_Y764insFQEA, V769_D770insASV, D770_N771insNPG, D770_N771insSVD, H773_V774insNPH, or any other in-frame exon 20 insertion mutation) by a local test that has been analytically validated per local authority guidelines....

...Have a documented EGFR in-frame exon 20 insertion mutations 3....

The weighted hazard ratio (HR) comparing mobocertinib to amivantamab was 0.74 (0.51-1.07) for IRC-assessed PFS, 0.92 (0.57-1.48) for OS, and 0.59 (0.30-1.18) for INV-assessed DoR….MAIC analysis showed that mobocertinib and amivantamab had similar efficacy in patients with NSCLC harboring EGFR ex20ins mutations whose disease progressed during or after platinum-based chemotherapy.

Inclusion criteria: ≥18 years old; diagnosis of stage IIIB-IV NSCLC with EGFR exon20ins mutations between 1 Jan 2017 and 30 Nov 2021; received mobocertinib....The median PFS (95% confidence interval [CI]) was 4.76 months (3.98, 6.21; N: 105). The ORR was 20.0%, and the median DOR was 8.34 months (95% CI: 3.61, 9.49; N: 21).

Among EGFR ex20ins patients, 71/84 had stage IV disease....Nine out of 10 patients who received poziotinib and all 5 patients who received mobocertinib had either a partial response or stable disease, whereas 3/7 patients who received afatinib had stable disease.

Mobocertinib has shown efficacy in PPP with EGFR ex20ins NSCLC.

Compared to standard regimens in the weighted population, mobocertinib prolonged overall survival (OS, median [95% CI] = 9.8 [4.3-13.7] vs. 20.2 [14.9-25.3] months; hazard ratio [HR] = 0.42 [0.25-0.69], p = 0.0035), progression-free survival (PFS, median [95% CI] = 2.6 [1.5-5.7] vs. 7.3 [5.6-8.8] months; HR = 0.28 [0.18-0.44], p < 0.0001), and time to treatment discontinuation (median [95% CI] = 2.1 [1.2-3.1] vs. 7.4 [6.4-8.5] months; HR = 0.34 [0.18-0.65], p = 0.0004)....Mobocertinib was associated with an improved cORR and prolonged PFS and OS compared to standard treatments for patients with EGFR ex20ins-positive NSCLC previously treated with platinum-based chemotherapy.

The mobocertinib group included platinum-pretreated patients with advanced EGFR ex20ins non-small cell lung cancer (NSCLC) receiving mobocertinib 160 mg QD in an ongoing, single-arm, phase 1/2 clinical trial (NCT02716116; n = 114)….In the mobocertinib and RWD groups, respectively, cORR was 35.1 % and 11.9 % (odds ratio: 3.75 [95 % confidence interval (CI): 2.05, 6.89]); median PFS was 7.3 and 3.3 months (hazard ratio [HR]: 0.57 [95 % CI: 0.36, 0.90]); and median OS was 24.0 and 12.4 months (HR: 0.53 [95 % CI: 0.33, 0.83]) after weighting....Mobocertinib showed substantially improved outcomes versus an external control group using available therapies in platinum-pretreated patients with EGFR ex20ins-mutant NSCLC.

To estimate lifetime health benefits of mobocertinib and current treatment options for patients with locally advanced or metastatic non-small cell lung cancer harboring epidermal growth factor receptor exon 20 insertion mutation (EGFRex20ins-mNSCLC)...In the base-case analysis, mobocertinib could gain 0.722 (vs. PEM/CDDP/BEV) to 0.862 years (vs. high-dose osimertinib) of PFLYs, 1.269 (vs. high-dose osimertinib) to 1.993 years (vs. DTX/CDDP) of PPLYs...Mobocertinib had additional lifetime health benefits (PFLYs, PPLYs, and QALYs) compared with existing, second-line treatments of EGFRex20ins-mNSCLC in China.

Post-platinum patients with EGFRex20ins aNSCLC remained on mobocertinib for 5 months in the EAP. Over half of patients had ≥2 orders of mobocertinib and a prolonged estimated TTD of 11 months, suggesting clinical benefit (i.e., response or stable disease). Mobocertinib appears effective in a real-world setting.

The cORR was 28.1%, median duration of response was 15.8 mo, and median progression-free survival was 7.3 mo (all per IRC; Table). Confirmed responses were observed in all prespecified subgroups….At more than 2 years of follow-up in the Phase 1/2 trial, mobocertinib continues to demonstrate clinically meaningful benefit for PPP with EGFR ex20ins+ mNSCLC, with a manageable safety profile.

Most baseline variables were balancedafter weighting. For mobocertinib vs weighted RWD, cORR was 35% vs 0%, medianPFS was 7.3 vs 2.5 months, and median OS was 24.0 vs 9.8 month. Among platinum-pretreated pts with EGFR ex20ins+ NSCLC, mobo-certinib showed significantly higher cORR, and prolonged PFS and OS compared totreatment in the real-world setting, with or without weighting to match baselinevariables.

Median overall survival was 24.0 months (95% CI, 14.6-28.8)…. In this open-label, phase 1/2 nonrandomized clinical trial, mobocertinib was associated with clinically meaningful benefit in patients with previously treated EGFRex20ins-positive mNSCLC, with a manageable safety profile.

This study describes an indirect comparison of clinical outcomes for platinum-pretreated patients with EGFRex20ins+ NSCLC treated with mobocertinib in a clinical trial vs. standard of care (SoC) from real-world data (RWD)….In the weighted cohort, cORR for mobocertinib vs. RWD was 35 % vs. 12%, median PFS was 7.3 vs. 3.3 mo, and median OS was 24.0 vs. 12.4 mo, respectively....Mobocertinib was associated with significant improvements in cORR, PFS, and OS compared to SoC used in the in platinum-pretreated patients with EGFRex20ins+ NSCLC.

The phase I/II study (NCT02716116) of mobocertinib 160 mg QD in platinum-pretreated pts (PPP) with EGFRex20ins+ NSCLC, demonstrated a confirmed objective response rate (ORR) of 28% per independent review committee (IRC)…In PPP (N=114), ORR was 21% (95% CI: 8.0, 39.7) in pts with AEs leading to dose reductions and 31% (21.1, 41.5) in those without; DoR was 5.7 mo (3.7, not reached [NR]) and 17.5 mo (7.4, NR); PFS was 5.9 mo (3.7, 11.0) and 7.3 mo (5.5, 10.8), respectively.

The 3-part, open-label, phase 1/2, multicenter study...evaluated mobocertinib in patients with EGFR ex20ins+ metastatic NSCLC….Confirmed ORR per IRC in PPP was 28% [95% CI: 20–37]; DCR was 78% [95% CI: 69–85]. Confirmed ORR per IRC was 25% in PPP with prior anti-PD(L)-1 therapy and 30% in PPP without prior anti-PD(L)-1 therapy....Efficacy of mobocertinib was similar in patients with and without prior anti-PD(L)-1 therapies.

A phase 1/2, open-label, multicenter, study of mobocertinib (NCT02716116) evaluated a dose-expansion EGFR ex20ins+ metastatic NSCLC cohort who progressed after response or stable disease for ≥6 months on any prior EGFR TKI therapy….Mobocertinib treatment had a clinically meaningful benefit for patients with EGFR ex20ins+ metastatic NSCLC with ≥6-month disease control on prior EGFR TKI.

The EXCLAIM extension cohort of the phase 1/2 multicenter study (NCT02716116) evaluated mobocertinib 160 mg orally once daily in previously treated metastatic NSCLC patients with EGFR ex20ins….Clinically meaningful improvements from baseline in QLQ-LC13 symptom scores (defined as ≥10-point decrease in symptom scores) were observed for core lung cancer symptoms of dyspnea in 54.4% of patients, coughing in 46.7%, and pain in chest in 38.9%.

Among 28 EGFRex20ins patients treated at 160 mg/d, the investigator-assessed confirmed response rate was 43% (12/28; 95% confidence interval, 24%–63%) with median duration of response of 14 months (5.0–not reached) and median progression-free survival of 7.3 months (4.4–15.6). Mobocertinib demonstrated antitumor activity in patients with diverse EGFRex20ins variants with a safety profile consistent with other EGFR inhibitors.

Pts with EGFR ex20ins+ mNSCLC, ECOG status 0–1, and ≥1 prior line of therapy for locally advanced/metastatic disease received mobocertinib 160 mg QD….Confirmed ORR per IRC was 28%, including 1 complete response (CR); disease control rate (DCR) was 78% [95% CI: 69–85]....Confirmed responses were seen in all prespecified subgroups in PPP and EXCLAIM....Mobocertinib demonstrated clinically meaningful benefit for pts with EGFR ex20ins+ mNSCLC in PPP and EXCLAIM cohorts, with a manageable safety profile.

Takeda Pharmaceutical Company Limited...today announced new data from the Phase 1/2 trial of mobocertinib (TAK-788) orally administered in previously treated patients with epidermal growth factor receptor (EGFR) Exon20 insertion+ metastatic non-small cell lung cancer (mNSCLC)...clinically meaningful responses, with a confirmed objective response rate of 35% as assessed by investigator and 28% as assessed by an independent review committee (IRC)...Responses shown with mobocertinib were durable, with a median duration of response of 17.5 months as assessed by IRC

Mobocertinib demonstrated clinically meaningful benefit in previously treated patients with NSCLC and EGFRex20ins mutations, with a manageable safety profile.

Mobocertinib demonstrated antitumor activity in pts with advanced NSCLC with EGFR exon20ins. The safety profile for mobocertinib was consistent with other EGFR TKIs.

A total of 99 pts were included, n=28 TAK-788 and n=71 RWD; mean age 62/65 y; male 25%/46%...Specifically, after weighting, median PFS for TAK-788 vs RWD is 7.3 vs 3.5 mo, and ORR is 43% vs 13%...Despite a more heavily pretreated pt population, the efficacy of TAK-788 in pts with refractory NSCLC with EGFR exon 20 insertions appears better than other second-line treatment options used in the real-world setting.

Of 14 evaluable pts, 3 had PR (80 mg, n = 2, both confirmed; 120 mg, single PR awaiting confirmation), 6 had SD (40 mg, n = 3; 80 mg, n = 2; 120 mg, n = 1), and 5 had PD as best response (40 mg, n = 3; 80 mg, n = 1; 120 mg, n = 1); all pts with PR or SD had EGFR exon 20 insertions...TAK-788 exhibits antitumor activity in pts with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs.

Confirmed ORR per IRC was 28%, including 1 complete response (CR); disease control rate (DCR) was 78% [95% CI: 69–85]; median duration of response (DOR) was 17.5 mo...Mobocertinib demonstrated clinically meaningful benefit for pts with EGFR ex20ins+ mNSCLC in PPP and EXCLAIM cohorts, with a manageable safety profile.

...and 5 had PD as best response (40 mg, n = 3; 80 mg, n = 1; 120 mg, n = 1); all pts with PR or SD had EGFR exon 20 insertions....TAK-788 exhibits antitumor activity in pts with EGFR exon 20 insertions with an AE profile consistent with other EGFR TKIs.

The in vitro and in vivo activity of mobocertinib was evaluated in engineered and patient-derived models harboring diverse EGFRex20ins mutations. Mobocertinib inhibited viability of various EGFRex20ins-driven cell lines more potently than approved EGFR TKIs and demonstrated in vivo antitumor efficacy in patient-derived xenografts and murine orthotopic models.