FDA grants Breakthrough Therapy Designation to Roche’s inavolisib
for advanced hormone receptor-positive, HER2-negative breast cancer
with a PIK3CA mutation
- The designation is based on
Phase III INAVO120 results, showing the inavolisib-based regimen
more than doubled progression-free survival compared with
palbociclib and fulvestrant alone in the first-line
setting1
- Approximately 40% of people
with HR-positive breast cancer have a
PIK3CA mutation and often face
poorer prognosis and resistance to endocrine
treatment2,3
- This is the 29th
Breakthrough Therapy Designation for Roche’s oncology portfolio, a
testament to our enduring ambition to deliver transformative
medicines for
patients4
Basel, 21 May 2024 - Roche (SIX: RO, ROG; OTCQX: RHHBY)
announced today that the U.S. Food and Drug Administration (FDA)
has granted Breakthrough Therapy Designation for inavolisib, an
investigational oral therapy, in combination with palbociclib
(Ibrance®) and fulvestrant, for the treatment of adult patients
with PIK3CA-mutated, hormone receptor-positive, human
epidermal growth factor receptor 2-negative, locally advanced or
metastatic breast cancer, following recurrence on or within 12
months of completing adjuvant endocrine treatment.
“We are pleased that the FDA granted Breakthrough Therapy
Designation for inavolisib in recognition of the substantial
clinical benefit observed with this regimen,” said Levi Garraway,
M.D., Ph.D., Roche’s Chief Medical Officer and Head of Global
Product Development. “This promising inavolisib-based regimen could
transform the PI3K inhibitor class, potentially becoming the
standard of care for this patient population in the first-line
setting.”
Breakthrough Therapy Designation is designed to accelerate the
development and regulatory review of medicines intended to treat
serious or life-threatening conditions where preliminary clinical
evidence has indicated they may demonstrate substantial improvement
over existing therapies.5
The FDA’s decision is based on positive Phase III INAVO120
results, which showed the inavolisib-based regimen reduced the risk
of disease worsening or death (progression-free survival) by 57%
compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3
months; hazard ratio [HR]=0.43, 95% CI: 0.32-0.59,
p<0.0001).1 Overall survival (OS) data were immature
at this time, but a clear positive trend has been observed
(stratified HR=0.64, 95% CI: 0.43-0.97, p=0.0338 (boundary of
0.0098).1 Follow-up for OS will continue to the next
analysis. These data reinforce the potential for this
inavolisib-based regimen to benefit patients with
PIK3CA-mutated locally advanced or metastatic breast
cancer.1
PIK3CA is one of the most commonly mutated genes in
advanced or metastatic breast cancer.6 Despite the
prevalence of PIK3CA mutations, many patients are not
tested until later in their treatment journey.7 Early
testing for PIK3CA prior to initiating first-line
treatment helps clinicians make a personalised treatment
decision.7,8
Data from INAVO120 are also being submitted to other global
health authorities, including the European Medicines Agency.
Inavolisib is currently being investigated in three
company-sponsored Phase III clinical studies (INAVO120, INAVO121,
INAVO122) in PIK3CA-mutated locally advanced or metastatic
breast cancer in various combinations.9-11 We continue
to evaluate potential clinical development programme expansion
opportunities to address patient unmet needs in various tumour
types across oncology.
About inavolisib
Inavolisib is an investigational, oral targeted treatment with
best-in-class potential that could provide well-tolerated, durable
disease control and potentially improved outcomes for people with
PIK3CA-mutated, hormone receptor-positive, human epidermal
growth factor receptor 2-negative, locally advanced or metastatic
breast cancer, who often have a poor prognosis and are in urgent
need of new treatment options.1-3 Inavolisib has been
designed to help minimise the overall burden and toxicity of
treatment and is differentiated from other PI3K inhibitors due to
its high potency and specificity for the PI3K alpha isoform versus
other isoforms, and unique mechanism of action that facilitates the
degradation of mutated PI3K alpha.12,13
About the INAVO120 study
The INAVO120 study [NCT04191499] is a Phase III, randomised,
double-blind, placebo-controlled study evaluating the efficacy and
safety of inavolisib in combination with palbociclib and
fulvestrant versus placebo plus palbociclib and fulvestrant in
people with PIK3CA-mutated, hormone receptor
(HR)-positive, human epidermal growth factor receptor 2
(HER2)-negative, locally advanced or metastatic breast cancer whose
disease progressed during treatment or within 12 months of
completing adjuvant endocrine therapy and who have not
received prior systemic therapy for metastatic
disease.9
The study included 325 patients, who were randomly assigned to
either the investigational or control treatment arm.9
The primary endpoint is progression-free survival, as assessed by
investigators, defined as the time from randomisation in the
clinical trial to the time when the disease progresses, or a
patient dies from any cause.9 Secondary endpoints
include overall survival, objective response rate, and clinical
benefit rate.9
Beyond INAVO120, inavolisib is currently being investigated in
two additional company-sponsored Phase III clinical studies in
PIK3CA-mutated locally advanced or metastatic breast
cancer in various combinations:
- in combination with fulvestrant versus alpelisib plus
fulvestrant in HR-positive/HER2-negative breast cancer post
cyclin-dependent kinase 4/6 inhibitor and endocrine combination
therapy (INAVO121; NCT05646862), and
- in combination with pertuzumab plus trastuzumab for
subcutaneous injection (SC) versus pertuzumab plus trastuzumab for
SC and optional physician's choice of endocrine therapy as a
maintenance treatment in HER2-positive disease (INAVO122;
NCT05894239).10,11
About hormone receptor (HR)-positive breast
cancer
HR-positive breast cancer is the most prevalent type of all
breast cancers, accounting for approximately 70% of
cases.14,15 A defining feature of HR-positive breast
cancer is that its tumour cells have receptors that attach to
one or both hormones – oestrogen or progesterone – which
can contribute to tumour growth. People diagnosed with
HR-positive metastatic breast cancer often face the risk of disease
progression and treatment side effects, creating a need for
additional treatment options.15-17 The PI3K signalling
pathway is commonly dysregulated in HR-positive breast cancer,
often due to activating PIK3CA mutations, which have been
identified as a potential mechanism of intrinsic resistance to
standard of care endocrine therapy in combination with
cyclin-dependent kinase 4/6 inhibitors.3
About Roche in breast cancer
Roche has been advancing breast cancer research for more than 30
years with the goal of helping as many people with the disease as
possible. Our medicines, along with companion diagnostic tests,
have contributed to bringing breakthrough outcomes in HER2-positive
and triple-negative breast cancers. As our understanding of breast
cancer biology rapidly improves, we are working to identify new
biomarkers and approaches to treatment for other subtypes of the
disease, including oestrogen receptor-positive breast cancer, which
is a form of hormone receptor-positive breast cancer, the most
prevalent type of all breast cancers.14
About Roche
Founded in 1896 in Basel, Switzerland, as one of the first
industrial manufacturers of branded medicines, Roche has grown into
the world’s largest biotechnology company and the global leader in
in-vitro diagnostics. The company pursues scientific excellence to
discover and develop medicines and diagnostics for improving and
saving the lives of people around the world. We are a pioneer in
personalised healthcare and want to further transform how
healthcare is delivered to have an even greater impact. To provide
the best care for each person we partner with many stakeholders and
combine our strengths in Diagnostics and Pharma with data insights
from the clinical practice.
In recognising our endeavour to pursue a long-term perspective
in all we do, Roche has been named one of the most sustainable
companies in the pharmaceuticals industry by the Dow Jones
Sustainability Indices for the fifteenth consecutive year. This
distinction also reflects our efforts to improve access to
healthcare together with local partners in every country we
work.
Genentech, in the United States, is a wholly owned member of the
Roche Group. Roche is the majority shareholder in Chugai
Pharmaceutical, Japan.
For more information, please visit www.roche.com.
All trademarks used or mentioned in this release are protected
by law.
References
[1] Jhaveri K, et al. Phase III study of inavolisib or placebo in
combination with palbociclib and fulvestrant in patients with
PIK3CA-mutant, hormone receptor-positive, HER2-negative
locally advanced or metastatic breast cancer: INAVO120 primary
analysis. Presented at San Antonio Breast Cancer Symposium, 2023
December 5-9; San Antonio, USA. Abstract #GS03-13.
[2] Fillbrunn M, et al. PIK3CA mutation status,
progression and survival in advanced HR+/HER2- breast cancer: a
meta-analysis of published clinical trials. BMC Cancer.
2022;22:1002.
[3] Anderson E, et al. A Systematic Review of the Prevalence and
Diagnostic Workup of PIK3CA Mutations in HR+/HER2– Metastatic
Breast Cancer. Int J Breast Cancer. 2020;2020:3759179.
[4] U.S. Food and Drug Administration. Breakthrough Therapy
Approvals [Internet; cited 2024 May]. Available from:
https://www.fda.gov/drugs/nda-and-bla-approvals/breakthrough-therapy-approvals.
[5] U.S. Food and Drug Administration. Breakthrough Therapy
[Internet; cited 2024 May]. Available from:
https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy.
[6] Miron A, et al. PIK3CA mutations in in situ and
invasive breast carcinomas. Cancer Res. 2010;70(14):5674–8.
[7] Princic N, et al. Abstract P1-18-18: PIK3CA mutation testing
prevalence among post-menopausal (PM) women with hormone receptor
positive and human epidermal growth factor receptor 2 negative
(HR+/HER2-) metastatic breast cancer (mBC) using real world data.
Cancer Res. 2020;80(4):P1-18-18.
[8] Wales Cancer Network. PIK3CA-mutated breast cancer clinical
guidance document [Internet; cited 2024 May]. Available from:
https://executive.nhs.wales/functions/networks-and-planning/cancer/wcn-documents/mutated-breast-cancer-clinical-guidance-document//.
[9] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety
of Inavolisib + Palbociclib + Fulvestrant vs Placebo + Palbociclib
+ Fulvestrant in Patients With PIK3CA-Mutant, Hormone
Receptor-Positive, Her2-Negative, Locally Advanced or Metastatic
Breast Cancer (INAVO120) [Internet; cited 2024 May]. Available
from: https://classic.clinicaltrials.gov/ct2/show/NCT04191499.
[10] ClinicalTrials.gov. A Study Evaluating the Efficacy and Safety
of Inavolisib Plus Fulvestrant Compared With Alpelisib Plus
Fulvestrant in Participants With HR-Positive, HER2-Negative,
PIK3CA Mutated, Locally Advanced or Metastatic Breast
Cancer Post CDK4/6i and Endocrine Combination Therapy (INAVO121)
[Internet; cited 2024 May]. Available from:
https://classic.clinicaltrials.gov/ct2/show/NCT05646862.
[11] ClinicalTrials.gov. A Study to Evaluate the Efficacy and
Safety of Inavolisib in Combination With Phesgo Versus Placebo in
Combination With Phesgo in Participants With
PIK3CA-Mutated HER2-Positive Locally Advanced or
Metastatic Breast Cancer [Internet; cited 2024 May]. Available
from: https://classic.clinicaltrials.gov/ct2/show/NCT05894239.
[12] Juric D, et al. A phase I/Ib study of inavolisib (GDC-0077) in
combination with fulvestrant in patients (pts) with
PIK3CA-mutated hormone receptor-positive/HER2-negative
(HR+/HER2–) metastatic breast cancer. Presented at San Antonio
Breast Cancer Symposium, 2020 December 7-10; San Antonio, USA.
Abstract #P5-17-05.
[13] Hong R, et al. GDC-0077 is a selective PI3K alpha inhibitor
that demonstrates robust efficacy in PIK3CA mutant breast cancer
models as a single agent and in combination with standard of care
therapies. Cancer Res. 2018;78(4):4-14.
[14] National Cancer Institute: Surveillance, Epidemiology and Ends
Result Program. Cancer Stat Facts: Female Breast Cancer Subtypes
[Internet; cited 2024 May]. Available from:
https://seer.cancer.gov/statfacts/html/breast-subtypes.html.
[15] Lim E, et al. The natural history of hormone receptor-positive
breast cancer. Oncology (Williston Park).
2012;26(8):688-94,696.
[16] Tomas R and Barrios CH. Optimal management of hormone receptor
positive metastatic breast cancer in 2016. Ther Adv Med Oncol.
2015;7(6):304-20.
[17] Galipeau N, et al. Understanding key symptoms, side effects,
and impacts of HR+/HER- advanced breast cancer: qualitative study
findings. J Patient-Rep Outcomes. 2019;3(1):10.
Roche Global Media Relations
Phone: +41 61 688 8888 / e-mail: media.relations@roche.com
Hans Trees,
PhD
Phone: +41 79 407 72 58 |
Sileia
Urech
Phone: +41 79 935 81 48
|
Nathalie
Altermatt
Phone: +41 79 771 05 25 |
Simon
Goldsborough
Phone: +44 797 32 72 915
|
Karsten
Kleine
Phone: +41 79 461 86 83 |
Nina
Mählitz
Phone: +41 79 327 54 74
|
Kirti
Pandey
Phone: +49 172 6367262 |
Yvette
Petillon
Phone: +41 79 961 92 50
|
Dr. Rebekka Schnell
Phone: +41 79 205 27 03
Roche Investor Relations
Dr. Bruno
Eschli
Phone: +41 61 68-75284
e-mail: bruno.eschli@roche.com
|
Dr. Sabine
Borngräber
Phone: +41 61 68-88027
e-mail: sabine.borngraeber@roche.com
|
Dr. Birgit
Masjost
Phone: +41 61 68-84814
e-mail: birgit.masjost@roche.com |
|
Investor Relations North America
Loren
Kalm
Phone: +1 650 225 3217
e-mail: kalm.loren@gene.com
|
- 21052024_MR_FDA_BTD_inavolisib_en
Roche (LSE:0QQ6)
Historical Stock Chart
From May 2024 to Jun 2024
Roche (LSE:0QQ6)
Historical Stock Chart
From Jun 2023 to Jun 2024