Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as TAK-788, AP32788
Mobocertinib · 4 trials · 4 indications
PFS is defined as the time interval from the date of randomization until the first date at which the criteria for progressive disease (PD) according to RECIST Version 1.1 are met or death, whichever occurs first.
As planned, this pharmacokinetic (PK) outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A.
As planned, this PK outcome measure was only assessed in Part A for midazolam 3 mg oral solution.
As planned, this PK outcome measure was only assessed in Part A for midazolam 1 mg intravenous infusion.
The RP2D was the maximum tolerated dose (MTD) or less. The MTD was declared when at least 9 participants were evaluable in the study and 6 participants were evaluable at the current dose, and the current dose was recommended for the next cohort. The dose recommended for use in phase 2 part was analyzed on the basis of the safety and tolerability data obtained in phase 1 part of the study.
Confirmed ORR is defined as percentage of participants who were confirmed to had achieved complete response (CR) or partial response (PR) per IRC using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 after the initiation of study treatment. Confirmed responses were responses that persisted on repeat imaging \>=4 weeks after initial response. CR (target lesion response): disappearance of all extranodal target lesions, all pathological lymph nodes must have decreased to \<10 millimeter (mm) in short axis. CR (non-target lesion response): disappearance of all extranodal nontarget lesions, all lymph nodes must be nonpathological in size (\<10 mm short axis) and normalization of tumor marker level. PR (target lesions): at least 30% decrease in sum of the longest diameters (SLD) of target lesions, taking as reference baseline sum diameters. The SLD must also demonstrate an absolute increase of at least 5 mm.
| Arm | Type | Description |
|---|---|---|
| TAK-788 Group (Arm A) | EXPERIMENTAL | TAK-788 160 milligram (mg) with or without food, capsules, orally, once daily until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. |
| Platinum-based Chemotherapy Group (Arm B) | ACTIVE_COMPARATOR | Pemetrexed 500 milligram per meter square (mg/m\^2) plus cisplatin 75 mg/m\^2, infusion, IV, once on Day 1 of 21-day cycle pemetrexed 500 mg/m\^2 plus carboplatin, infusion, IV, once at a dose calculated to produce area under curve (AUC) of 5 milligram\*minute per milliliter (mg\*min/mL) on Day 1 of 21-day cycle until the participants experience PD as assessed by blinded IRC, intolerable toxicity, or another discontinuation criteria. Pemetrexed/cisplatin or pemetrexed/carboplatin will be repeated every 3 weeks for 4 cycles, followed by maintenance treatment with pemetrexed 500 mg/m\^2, on Day 1 of a 21-day cycle thereafter. |
| Part A: Midazolam + TAK-788 | EXPERIMENTAL | Midazolam 3 mg, solution, orally, once on Days 1 and 24 and midazolam 1 mg, infusion, intravenously, once on Days 2 and 25 along with TAK-788 160 mg, capsule, orally, once daily from Day 3 through 30 in Cycle 1. |
| Part B: TAK-788 | EXPERIMENTAL | TAK-788 160 mg, capsules, orally, once daily in a 28-day treatment cycle from Cycle 2 to Cycle 24, or until progressive disease (PD), intolerable toxicity, or another discontinuation criterion is met, whichever is sooner. Eligible participants from Part A may enter into Part B. Based on the investigator's opinion, if a participant continues to experience clinical benefit, treatment with TAK-788 may be continued after PD. |
| Mobocertinib, Phase 1 Part | EXPERIMENTAL | Mobocertinib 40 milligrams (mg) (as the starting dose), capsules, orally, once daily on Days 1-28 of each 28-day treatment cycle for up to disease progression or intolerable toxicity, or another discontinuation criterion, and increasing until 160 mg, once daily (for up to approximately 10-12 cycles). |
| Mobocertinib, Phase 2 Part | EXPERIMENTAL | Mobocertinib 160 mg, once daily, for up to approximately 10-12 cycles. |
| Part 1: Dose Escalation Component | EXPERIMENTAL | TAK-788 treatment for participants with advanced NSCLC. |
| Part 2: Expansion Cohort 1 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have either not received or not shown an objective response to an EGFR tyrosine kinase inhibitors (TKI), and who have no active, measurable central nervous system (CNS) metastases. |
| Part 2: Expansion Cohort 2 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with HER2 exon 20 activating insertions or point mutations and no active, measurable CNS metastases. |
| Part 2: Expansion Cohort 3 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions or HER2 exon 20 activating insertions or point mutations and active, measurable CNS metastases. |
| Part 2: Expansion Cohort 4 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with other targets against which TAK-788 is active (examples include EGFR exon 19 deletions or exon 21 substitutions \[with or without T790M mutations\] and other uncommon EGFR activating mutations), without active CNS metastases. |
| Part 2: Expansion Cohort 5 | EXPERIMENTAL | TAK-788 treatment for NSCLC participants with EGFR exon 20 activating insertions, who have previously shown an objective response to an EGFR TKI and subsequently progressed without active CNS metastases. |
| Part 2: Expansion Cohort 6 | EXPERIMENTAL | TAK-788 treatment NSCLC participants with EGFR exon 20 activating insertions, who have not received prior systemic anticancer treatment for locally advanced or metastatic disease without active CNS metastases |
| Part 2: Expansion Cohort 7 | EXPERIMENTAL | TAK-788 treatment for participants with solid tumors other than NSCLC with EGFR/HER2 mutations against which TAK-788 is active without active CNS metastases. |
| Part 3: Extension Cohort | EXPERIMENTAL | TAK-788 treatment for participants with previously treated locally advanced or metastatic NSCLC whose tumors harbor EGFR exon 20 insertion mutations. |
| Name | Type | Description |
|---|---|---|
| TAK-788 | DRUG | TAK-788 capsule |
| Pemetrexed | DRUG | Pemetrexed IV infusion |
| Cisplatin | DRUG | Cisplatin IV infusion |
| Carboplatin | DRUG | Carboplatin IV infusion |
| Midazolam | DRUG | Midazolam Oral Solution and Midazolam Intravenous Infusion. |
| Mobocertinib | DRUG | Mobocertinib capsule. |
Inclusion Criteria: * Male or female adult patients (aged 18 years or older) * Histologically or cytologically confirmed nonsquamous cell locally advanced not suitable for definitive therapy, recurrent, or metastatic (Stage IV) NSCLC * Documented epidermal growth factor receptor (EGFR) in-frame exo...
Mobocertinib is being developed for advanced or metastatic non-small cell lung cancer (NSCLC), specifically in patients whose tumors have EGFR exon 20 insertion mutations. It is an oral small molecule studied as a first-line treatment versus platinum-based chemotherapy and in earlier-phase studies in adults with NSCLC.
Mobocertinib targets EGFR, the epidermal growth factor receptor. It is an EGFR inhibitor, a small molecule designed to inhibit EGFR signaling in tumors driven by EGFR alterations such as exon 20 insertion mutations. Its clinical program is biomarker-selected, enrolling patients whose NSCLC carries these EGFR mutations.
Mobocertinib is developed by Takeda Pharmaceutical Company Limited, which trades under the ticker TAK. Takeda sponsors the clinical program, including the Phase 3 first-line study and the earlier-phase trials in non-small cell lung cancer.
Mobocertinib is in Phase 3 development. The Phase 3 trial NCT04129502 compares it as first-line treatment versus platinum-based chemotherapy in NSCLC with EGFR exon 20 insertion mutations. It is investigational and is also being studied in Phase 1 trials, including NCT02716116, NCT03807778, and NCT04051827.
Mobocertinib has been studied in four registered trials. The Phase 3 NCT04129502 trial is active but not recruiting, with 354 patients. Phase 1 studies include NCT02716116 with 334 patients, NCT03807778 in Japanese adults with 53 patients, and the completed drug-drug interaction study NCT04051827 with 26 patients.
Yes, mobocertinib is also known as TAK-788. TAK-788 is the code name used in several trial titles, including the Phase 3 study NCT04129502 and the Phase 1 studies NCT02716116 and NCT04051827. Both names refer to the same investigational EGFR inhibitor developed by Takeda.