Enter Title

PI Pursuit

100

What information is contained within Section 1?

Indications and Usage

200

What information is contained within Section 5?

Warnings and Precautions

300

What are the specific populations contained within Section 8 of the EXKIVITY PI?

Pregnancy, Lactation, Females and Males of Reproductive Potential, Pediatric Use, Geriatric Use, Renal Impairment, and Hepatic Impairment.

400

What section is the MOA in and what is the MOA of Exkivity?

Section 12, Mobocertinib is a kinase inhibitor of the epidermal growth factor receptor (EGFR) that irreversibly binds to and inhibits EGFR Exon20 insertion mutations at lower concentrations than wild type (WT) EGFR.

500

In which table can you find the dose modifications for Alunbrig and what is the dose modification for Hypertension?

Table 2

• Grade 3-withold ALunbrig until hypertension has recovered to Grade 1 or less (SBP  less than 140 mmHg and DBP less than 90 mmHg), then resume the same dose.
• Grade 3 Recurrence- withhold Alunbrig until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue.
• Grade 4- Withhold Alunbrig until recovery to Grade 1 or less, and resume at next lower dose (Table 1) or permanently discontinue.
• Recurrence of Grade 4- permanently discontinue Alunbrig for recurrence of Grade 4 hypertension.

CVA Mastery

100

The intracranial response rate was 3x higher with Alunbrig vs. Crizotinib. What was the IC-ORR of Alunbrig and Crizotinib?

78% vs. 26%

200

What does “Alunbrig reduced the risk of death by 57% vs. Crizotinib” translate to?

HR of 0.43

300

Finish the claim on Page 1 of the Exkivity CVA, “Exkivity (mobocertinib) is…”

The first and only oral therapy designed to target EGFR Exon20 insertion+ mNSCLC

400

On Page 2 of the Exkivity CVA, Exon20 insertions do what to the size of the ATP drug binding pocket

Reduce

500

The mPFS in a post hoc subgroup analysis in patients with any brain mets at baseline was what for Alunbrig and what for Crizotinib?

mPFS Alunbrig-24.0 months vs. mPFS Crizotinib- 5.6 months

Probing, Objection!

100

What is an appropriate probe after the objection, “I am concerned about the rates of ILD/Pneumonitis” from the Alunbrig Objection Handler.

Have you seen ILD/pneumonitis in your patients treated with Alunbrig?

200

What is an appropriate probe after the objection, “AN ORR of 28% doesn’t seem impressive compared to the results we’ve seen with other targeted therapies” from the Exkivity Objection Handler.

May I ask what type of responses you have typically seen with targeted TKIs in your clinical practice? What do you typically see for duration of response?

300

What is an appropriate probe(s) after the objection, “You don’t have efficacy data in patients after amivantamab” from the Exkivity Objection Handler.

• What sequencing data have you seen for patients with EGFR Exon20 insertion+ mNSCLC?

• What is your current algorithm for treating patients with EGFR Exon20 insertion+ mNSCLC?

400

What is the appropriate response to the objection, “Why can’t I use EXKIVITY® (mobocertinib) in the first-line setting like I do with most targeted therapies” from the Exkivity Objection Handler?

• Until 2021, there were no targeted treatment options
• The approved indication of EXKIVITY is based upon an accelerated approval and results from our registration Phase 1/2 clinical trial, which evaluated 114 patients with EGFR Exon20 insertion+ metastatic or locally advanced NSCLC who had progressed on or after platinum-based chemotherapy
• The EXKIVITY accelerated approval was based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s)

500

What is the appropriate probe and response to “Alectinib reported OS data at 5 years. How do the OS data for ALUNBRIG® (brigatinib) compare” from the Alunbrig Objection Handler?

Probe: What has your experience been regarding OS with the TKIs you have prescribed?

Response:

In the final analysis of the ALTA 1L trial—with 40.4 months of median follow-up in the ALUNBRIG arm—OS was assessed in all patients, including those with brain metastases

The 3-year OS rate was 71% (95% CI: 62, 78) with ALUNBRIG and 68% (95% CI: 59, 75) with crizotinib (HR=0.81; 95% CI: 0.53, 1.22; P=0.331)At the time of the final analysis, 47% (n=65/138) of patients in the crizotinib arm crossed over to receive ALUNBRIG. The crossover design means that, as crizotinib patients progress and switch to ALUNBRIG, the OS treatment effect may be diluted

In the final analysis, among patients with measurable brain metastases, ALUNBRIG reduced the risk of death by 57% vs crizotinib despite crossover (HR=0.42; 95% CI: 0.21, 0.89; P=0.020)

Disease State

100

Approximately how many patients may present with EGFR Exon20 insertions in the United States each year?

2,000-4,000

200

Brain mets have been reported in up to what percent of TKI treatment-naive patients with ALK+ mNSCLC?

35%

300

Brain mets can result in which of the following 3 things (also located on Page 2 of the Alunbrig 1L CVA)?

Reduced quality of life due to neurological, psychological, and physical impairments, severe symptoms such as headache, seizure, and stroke, and shorter overall survival.

400

What test can identify all EGFR Exon20 insertion+ mNSCLC mutations?

NGS

500

How are Exon20 insertions different than other EFGR mutations?

Exon20 insertions change the conformation of EGFR in a way that stabilizes the active form, the Exon20 insertion pushes the c-helix moves inward into an active position

Alunbrig Allstars!

100

What is the BIRC assessed mPFS of Alunbrig in ALTA 1L?

24 months

200

What was the rate of CPK elevation (all grades) in patients who received Alunbrig in ALTA 1L?

81%

300

If coadministration of a strong or moderate CYP3A inhibitor is unavoidable, what should the HCP do with the dose of Alunbrig?

Reduce

400

List all the Warnings and Precautions for Alunbrig

Interstitial Lung Disease (ILD)/Pneumonitis, Hypertension, Bradycardia, Visual Disturbance, Creatine Phosphokinase (CPK) Elevation, Pancreatic Enzyme Elevation, Hepatoxicity, Hyperglycemia, Photosensitivity, Embryo-Fetal Toxicity.

500

What is the most common adverse reaction in ≥10% of patients who received Alunbrig in ALTA 1L and what was the incidence rate of all grades?

Diarrhea at 53%