Table 2.

Mobocertinib Prior and Ongoing Clinical Trials

Trial	Phase	Trial Summary	Treatment Arms	Primary Outcomes
EXCLAIM 2 NCT04129502	III	Compare the effectiveness of mobocertinib as first-line treatment with platinum-based chemotherapy	Arm 1: mobocertinib 160mg daily Arm 2: Pemetrexed + Cisplatin or Pemetrexed + Carboplatin	PFS
NCT04056455	I	Use of mobocertinib in severe RI with baseline eGFR 15–29mL not on HD	Arm 1: single dose (80mg) of mobocertinib in patient with severe RI Arm 2: single dose (80mg) of mobocertinib in patient with normal renal function	Cmax, AUC, Tmax, t1/2z, volume of distribution, and clearance of mobocertinib and its active metabolites (AP32960 and AP32914) pre- and post-treatment
NCT04056468	I	Use of mobocertinib in moderate (Child-Pugh B) and/or severe (Child-Pugh C) HI	Arm 1: single dose (40mg) capsule of mobocertinib in patient with moderate HI Arm 2: single dose (40mg) capsule of mobocertinib in patient with severe HI Arm 3: single dose (40mg) capsule of mobocertinib in patient with normal hepatic function	Cmax, AUC, Tmax, t1/2z, and clearance of mobocertinib and its active metabolites (AP32960 and AP32914) pre- and post-treatment.
NCT03811834	I	Assessment of ABA and characterize mass balance, PK, metabolism, and [14C]-mobocertinib in healthy participants	Mobocertinib 160mg and [14C]-mobocertinib 50mcg + [14C]-mobocertinib 160mg	%F, percentage and amount of total radioactivity recovered and excreted in urine and feces, Cmax, Tmax, t1/2, AUC of [14C]-mobocertinib pre- and post-treatment, percentage change of [14C]-radioactivity in whole blood relative to plasma over time
NCT04441255	I	Assess the effects of high-fat meal on PK of mobocertinib in healthy participants	Arm 1: 160mg mobocertinib fasting on day 1 with a 10-day washout period followed by 160mg mobocertinib non-fasting. Arm 2: 160mg mobocertinib non-fasting on day 1 with a 10-day washout period followed by 160mg mobocertinib fasting.	Tmax, Cmax, AUC of mobocertinib and its active metabolites pre- and post-dose
NCT03482453	I	Assess the effects of low-fat meal on PK of mobocertinib and assess bioavailability of two DiC of mobocertinib in healthy participants	Arm 1: mobocertinib capsule or placebo fasting Arm 2: mobocertinib capsule under fed condition with low-fat meal Arm 3: mobocertinib capsule under fasted condition, 7 -day washout, mobocertinib under fed conditions with low-fat meal Arm 4: DiC under fasted condition, 7-day washout, DiC under fed conditions with low-fat meal	Cmax, Tmax, AUC, t1/2 of mobocertinib pre- and post-dose. Determine number of participants with TEAEs, serious AEs, clinically significant abnormal lab values and/or vital signs
NCT03928327	I	Assess the effects of itraconazole and rifampin on single-dose PK of mobocertinib and active metabolites (AP32960 and AP32914) in healthy participants	Arm 1: Single 20mg capsule mobocertinib (day 1 and day 5) + 200mg itraconazole (QD) (days 1–14) Arm 2: Mobocertinib 160mg capsule (day 1 and 7) + rifampin 600mg (QD) (days 1–13).	Comparison of Cmax, AUC, and Tmax of mobocertinib and its active metabolites pre- and post-treatment with concurrent use of itraconazole vs rifampin
NCT04051827	I	Assess the effects of PO mobocertinib on single oral and IV-dose PK of midazolam in patients with advanced NSCLC.	Single arm with two phases Phase 1: 3mg PO midazolam (day 1 and 24) + 1mg IV midazolam (day 2 and 25) + 160mg PO mobocertinib 160mg/day PO mobocertinib for up to 24 cycles	Assess AUC, Cmax and Tmax of midazolam during phase 1
NCT03807778	I	Assess the dose of mobocertinib that can be given to Japanese adults with NSCLC without causing AE; Determine if NSCLC improves after treatment.	Single arm with two phases Phase 1: dose escalation of mobocertinib starting at 40mg/day up to 160mg/day Phase 2: 160mg/day TAK-788 for approximately 10–12 cycles	RP2D and ORR of mobocertinib

Note: Data from these studies^16–24.

Abbreviations: PFS, Progression free survival; eGFR, estimated glomerular filtration rate; RI, renal impairment; HD, hemodialysis; HI, hepatic impairment; ABA, absolute bioavailability; PK, pharmacokinetics; 14C, carbon-14; NSCLC, non-small cell lung cancer; EGFRex20ins, EGFR exon 20 insertion mutations; Tmax, time to reach maximum plasma concentration; Cmax, maximum plasma concentration; AUC, area under the plasma concentration time curve; t1/2z, terminal disposition phase half-life; %F, percent absolute oral bioavailability; AE, adverse events; RP2D, recommended phase 2 dose; DiC, dose-in-capsule.