Bring the potential of ROZLYTREK® to life

ROZLYTREK delivers clinically meaningful responses in NTRK fusion+ solid tumours, irrespective of baseline CNS metastases1,2

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ROZLYTREK delivers clinically meaningful responses in NTRK fusion+ solid tumours, irrespective of baseline CNS metastases1,2

NTRK fusions have emerged as actionable biomarkers in at least 25 types of tumours3–5

 

NTRK gene fusions by tumour type: salivary, thyroid, pancreatic, sarcoma, breast, lung, colorectal

The efficacy of ROZLYTREK for patients with NTRK fusion+ solid tumours was evaluated in three Phase I and II trials1,7

Study design

Efficacy was evaluated in 74 adult patients with PI3K NTRK fusion+ solid tumours1,7

Three Phase 1,2 ROZLYTREK trials in 74 TRK inhibitor-naïve patients with NTRK fusion+ solid tumours

* As evaluated by Blinded Independent Control Review.

† Three patients were enrolled into dose-escalation studies.

‡ With ≥6 months of follow up from date of first dose.

Safety was evaluated in 504 adult and paediatric patients across multiple biomarkers and tumour types as an integrated analysis of 4 clinical trials: ALKA-372-001, STARTRK-1, STARTRK-2 and STARTRK-NG1

ROZLYTREK was studied across a range of tumour types1

Series of icons showing ROZLYTREK was studied across a range of tumour types

Patient characteristics

ROZLYTREK was studied in a tumour-agnostic cohort of 74 adult patients with NTRK fusion+ solid tumours1

More than one-quarter of patients had CNS metastases1*

Brain icon showing patients that had CNS metastases at baseline

*As evaluated by investigator.

The majority of patients were female1

Diagram showing proportion of female, male and age of patients in the trial

Over one-third of patients were treatment naïve2

Bar chart showing proportion of treatment-naïve, 1 prior therapy, 2 or more prior therapies

The majority of patients had an ECOG-PS score of 0 or 11

Bar chart showing patient distribution for ECOG-PS 0, ECOG-PS 1 and ECOG-PS 2

ECOG-PS, Eastern Cooperative Oncology Group Performance Status.

More than half the patients were never smokers1

Cigarette icon showing percentage of patients who were never smokers

Efficacy

ROZLYTREK delivered clinically meaningful responses in NTRK fusion+ solid tumours, irrespective of baseline CNS metastases1,2

  • ORR
  • ORR
    CNS
  • DOR
  • PFS
  • OS

63.5% of patients treated responded to ROZLYTREK across all tumour types studied (N=74, 95% CI: 51.5, 74.4)1

ROZLYTREK addresses the oncogenic driver regardless of tumour type ORR:1

Series of icons showing ROZLYTREK objective response rate across multiple tumour types. Table showing ORR in ovarian, endometrial, cholangiocarcinoma, GI and neuroblastoma.

*95% confidence interval represents 4 patients with Secretory Breast Cancer only.

†A limited number of patients in some tumour types can cause uncertainty in the ORR estimate per tumour type. The ORR in the total population may not reflect the expected response in a specific tumour type.

ROZLYTREK delivered clinically meaningful responses in nearly two thirds of patients treated, irrespective of baseline CNS metastases2

Diagram of confirmed overall ORR, with and without baseline CNS metastases

*As evaluated by Blinded Independent Control Review.

Durable responses were observed in patients with NTRK fusion+ solid tumours1

Coloured strip showing median duration of response (DOR) with ROZLYTREK

*As evaluated by Blinded Independent Control Review.

ROZLYTREK demonstrated a clinically meaningful median PFS in patients with NTRK fusion+ solid tumours2

Median PFS (N=74)2

Graph showing median PFS with ROZLYTREK in NTRK fusion+ solid tumours

*As evaluated by Blinded Independent Control Review.

ROZLYTREK delivered nearly 2 years of survival in patients with NTRK fusion+ solid tumours2

Median OS (N=74)2

Graph showing median OS with ROZLYTREK in NTRK fusion+ solid tumours

*As evaluated by Blinded Independent Control Review.

CNS efficacy

ROZLYTREK crosses the blood–brain barrier and results in a clinically meaningful response in NTRK fusion+ patients with CNS metastasis1,7,8

ROZLYTREK is a weak substrate of P-glycoprotein and therefore is able to achieve clinically meaningful concentrations in the CNS1,9

ROZLYTREK offers high progression-free rates in the CNS8

ROZLYTREK CNS progression-free rate in all patients, with or without CNS mets at baseline

Baseline CNS metastases assessed by investigator. Time to CNS progression: only confirmed CNS progression counted as an event (death censored).

*As regular CNS scans were not mandated by the protocol, CNS follow-up of patients without baseline metastases was not comprehensive but based on symptomatic progression or routine CNS scans where customary.

The only TRK inhibitor designed to remain and deliver benefit to the CNS1,2,8

Brain icon with coloured strip showing IC-ORR, IC-CR and IC-PR with ROZLYTREK

* As evaluated by Blinded Independent Central Review.

† Patients with measurable baseline CNS metastases

‡ Four of eight patients had received intracranial radiotherapy to the brain within 2 months of their first dose of ROZLYTREK

IC-ORR shows efficacy in the brain10

Brain icon with strip showing ORR in CNS metastases can only be proven with intracranial response

ROZLYTREK delivers clinically meaningful responses in NTRK fusion+ solid tumours, irrespective of baseline CNS metastases:1,2

This medicinal product is subject to additional monitoring. This will allow quick identification of new safety information. Healthcare professionals are asked to report any suspected adverse reactions. See section 4.8 of the SmPC for details on how to report adverse reactions.

Footnotes

BICR, Blinded Independent Control Review; CI, confidence interval; CNS, central nervous system; CR, complete response; DOR, duration of response; ECOG, The Eastern Cooperative Oncology Group; ESMO, European Society for Medical Oncology; HR, hazard ratio; IC-CR, intracranial complete response; IC-DOR, intracranial duration of response; IC-ORR, intracranial objective response rate; IC-PR, intracranial partial response; ITT, intent-to-treat; MASC, mammary analogue secretory carcinoma; Miss, missing; MRP, multidrug resistance protein; NA, not applicable due to small number or lack of response; NE, not estimable; NSCLC, non-small cell lung cancer; NTRK, neurotrophic tyrosine receptor kinase; ORR, objective response rate; OS, overall survival; PD, progressive disease; PFS, progression-free survival; P-gp, permeability-glycoprotein; PR, partial response; QD, once-daily; ROS1, c-ros oncogene 1; TRK, tropomyosin receptor kinase; TTD, time to treatment discontinuation; TTNT, time to next treatment.

 

References

  1. ROZLYTREK Summary of Product Characteristics, 2020.
  2. Rolfo C, et al. Efficacy and safety of entrectinib in patients with NTRK fusion-positive (NTRK-fp) solid tumours: an updated integrated analysis. Presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, 29 May – 4 June 2020.
  3. Amatu A, et al. ESMO Open 2016;1:e000023. 
  4. Lange AM, et al. Cancers (Basel) 2018;10. 
  5. Vaishnavi A, et al. Cancer Discov 2015;5:25-34.
  6. Cocco E, et al. Nat Rev Clin Oncol 2018;15:731–747.
  7. Doebele RC, et al. Lancet Oncol 2020;21:271–282.
  8. John T, et al. Intracranial efficacy of entrectinib in patients with NTRK fusion-positive solid tumours and baseline CNS metastases. Presented at the ESMO Virtual Congress 2020, 19–21 September 2020.
  9. Fischer H, et al. Neuro Oncol 2020;22:819–829.
  10. Data on file. Genentech, Inc.