REG - GSK PLC - Jemperli FDA ODAC positive outcome

GSKAnnouncement

10/02/2023 07:00

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RNS Number : 5215P  GSK PLC  10 February 2023

9 February 2023, London UK

 

US FDA Advisory Committee votes in support of trials designed to evaluate
Jemperli (dostarlimab-gxly) as a potential treatment for mismatch
repair-deficient/microsatellite instability-high locally advanced rectal
cancer

 

·      US FDA also recently granted Fast Track designation to Jemperli
in this patient population

 

GSK plc (LSE/NYSE: GSK) today announced that the US Food and Drug
Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted 8 to 5 in
support of the question posed to the committee regarding whether data from two
proposed single-arm trials will be "sufficient to characterize the benefits
and risks" of Jemperli (dostarlimab-gxly) in the curative-intent setting for
patients with mismatch repair-deficient/microsatellite instability-high
(dMMR/MSI-H) locally advanced rectal cancer.

 

Hesham Abdullah, Senior Vice President, Global Head of Oncology Development,
GSK, said: "The Committee's positive vote in favour of our proposed clinical
trial programme for dostarlimab reinforces our plans to generate data in
support of a future US regulatory submission for the potential treatment of
patients with dMMR/MSI-H locally advanced rectal cancer, a patient population
with significant unmet medical needs and a standard of care that results in
serious quality of life concerns. We thank the committee for the constructive
dialogue and we look forward to continued interactions with FDA as we progress
our development programme."

 

The current standard of care (SoC) for patients with dMMR/MSI-H locally
advanced rectal cancer is neoadjuvant chemoradiotherapy (CRT) followed by
surgery and adjuvant chemotherapy. i  (#_edn1) Neoadjuvant CRT provides local
tumour control in most patients, but nearly one-third ultimately die from
distant metastasis ii  (#_edn2) . Additionally, SoC is associated with
long-term adverse effects, including bowel, urinary and sexual dysfunction,
secondary malignancy and infertility (i).

 

As part of its proposed clinical trial programme, GSK is initiating a global,
open-label, phase II clinical trial to investigate the efficacy and safety of
dostarlimab-gxly as monotherapy - as a replacement for chemotherapy, radiation
and/or surgery - for treatment-naïve patients with dMMR/MSI-H locally
advanced rectal cancer. The primary endpoint of GSK's proposed trial is
clinical complete response for 12 months (cCR12) as assessed by Independent
Central Review. Key secondary endpoints will include cCR for 36 months and
event-free survival for three years by investigator assessment. In addition,
the trial aims to confirm results generated in a separate ongoing
investigator-initiated trial by researchers at Memorial Sloan Kettering Cancer
Center (MSK). Researchers at MSK shared these findings in a late-breaking
presentation at the 2022 American Society of Clinical Oncology (ASCO) Annual
Meeting with simultaneous publication in The New England Journal of
Medicine.(i) GSK intends to use data from the Company's proposed trial,
alongside data from MSK's ongoing trial of 30 patients, to support a
supplemental Biologics License Application (sBLA) for accelerated regulatory
approval in this indication.

 

In January 2023, the US FDA granted dostarlimab-gxly Fast Track designation
for the treatment of dMMR/MSI-H locally advanced rectal cancer. Fast Track
designation is designed to accelerate the development and expedite the review
of potential new medicines to treat serious conditions with unmet medical
needs. In addition, the application could be eligible for priority review if
supported by clinical data at the time of the submission to the FDA.

 

About dMMR/MSI-H rectal cancer

Rectal cancer is a form of cancer that starts in the rectum, the final section
of the large intestine, and is often categorised as part of a group of cancers
called colorectal cancer. Colorectal cancer is the third most commonly
diagnosed cancer in the world. iii  (#_edn3) In the US, it is estimated that
approximately 20,220 individuals are diagnosed annually with rectal cancer iv 
(#_edn4) . Approximately 5-10% of all rectal cancers are dMMR/MSI-H, meaning
that they contain abnormalities that affect the proper repair of DNA when
copied in a cell. v  (#_edn5) Mismatch repair-deficient status is a biomarker
that has been shown to predict response to immune checkpoint blockade with
PD-1 therapy. vi  (#_edn6)  vii  (#_edn7) Tumours with this biomarker are most
commonly found in endometrial, colorectal and other gastrointestinal cancers
but may also be found in other solid tumours. viii  (#_edn8)  ix  (#_edn9)  x 
(#_edn10)

 

About Jemperli (dostarlimab-gxly)

Jemperli is a programmed death receptor-1 (PD-1)-blocking antibody that binds
to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1
and PD-L2. xi  (#_edn11)  GSK's ambition is for dostarlimab to become the
backbone of the Company's ongoing immuno-oncology-based research and
development programme when used alone and in combination with standard of care
and future novel cancer therapies, particularly in patients with currently
limited treatment options. Dostarlimab is being investigated in registrational
enabling trials as monotherapy and as part of combination regimens, including
in women with recurrent or primary advanced endometrial cancer, women with
Stage III or IV non-mucinous epithelial ovarian cancer, and patients with
other advanced solid tumours or metastatic cancers. Dostarlimab has not been
approved anywhere in the world as monotherapy for treatment-naïve patients
with dMMR/MSI-H locally advanced rectal cancer. The US FDA has granted
dostarlimab Fast Track designation for the treatment of dMMR/MSI-H locally
advanced rectal cancer.

 

Dostarlimab was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc.,
under a collaboration and exclusive license agreement signed in March 2014.
The collaboration has resulted in three monospecific antibody therapies that
have progressed into the clinic. These are: dostarlimab (GSK4057190), a PD-1
antagonist; cobolimab, (GSK4069889), a TIM-3 antagonist; and GSK4074386, a
LAG-3 antagonist. GSK is responsible for the ongoing research, development,
commercialisation, and manufacturing of each of these medicines under the
agreement.

 

Important Information for Jemperli in the EU

Indication

Jemperli is indicated as monotherapy for the treatment of adult patients with
mismatch repair deficient (dMMR)/microsatellite instability high (MSI H)
recurrent or advanced endometrial cancer that has progressed on or following
prior treatment with a platinum containing regimen.

Refer to the Jemperli
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli)  Reference
Information (https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli)  for
a full list of adverse events and the complete important safety information in
the EU.

GSK in oncology

GSK is committed to maximising patient survival through transformational
medicines. GSK's oncology pipeline is focused on immuno-oncology, tumour cell
targeting therapies and synthetic lethality. Our goal is to achieve a
sustainable flow of new treatments based on a diversified portfolio of
investigational medicines utilising modalities such as small molecules,
antibodies, and antibody-drug conjugates, either alone or in combination.

 

About GSK

GSK is a global biopharma company with a purpose to unite science, technology,
and talent to get ahead of disease together. Find out more at gsk.com/company
(https://www.gsk.com/en-gb/company/) .

 

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Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made
by GSK, including those made in this announcement, are subject to risks and
uncertainties that may cause actual results to differ materially from those
projected. Such factors include, but are not limited to, those described in
the Company's Annual Report on Form 20-F for 2021, GSK's Q4 Results for 2022
and any impacts of the COVID-19 pandemic.

 

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 i  (#_ednref1) Cercek A, Lumish M, Sinopoli J, et al. PD-1 blockade in
mismatch repair-deficient, locally advanced rectal cancer. N Engl J Med 2022;
386: 2363-76.

 ii  (#_ednref2) Smith JJ, et al. Rectal Cancer Consortium. Organ Preservation
in Rectal Adenocarcinoma: a phase II randomized controlled trial evaluating
3-year disease-free survival in patients with locally advanced rectal cancer
treated with chemoradiation plus induction or consolidation chemotherapy, and
total mesorectal excision or nonoperative management. BMC Cancer. 2015 Oct
23;15:767. doi: 10.1186/s12885-015-1632-z. PMID: 26497495; PMCID: PMC4619249.

 iii  (#_ednref3) Sung H, Ferlay J, Siegel RL, et al. Global Cancer Statistics
2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers
in 185 Countries. CA Cancer J Clin. 2021;71(3):209-249. doi:10.3322/caac.21660

 iv  (#_ednref4) SEER Explorer. SEER Explorer Application. Accessed February
9, 2023, from https://seer.cancer.gov/statistics-network/explorer/
(https://urldefense.com/v3/__https:/seer.cancer.gov/statistics-network/explorer/__;!!AoaiBx6H!0tSqcaP5l1bbD_4sQbzH0qIR9JoS6E_I-L9J8uefztIxr8i26wb_KISEKVmmjVFaAV4zNUIDODOS_pFQ90ZCRW6v9b79dw$)
.

 v  (#_ednref5) Cercek A, et al. Mismatch Repair-Deficient Rectal Cancer and
Resistance to Neoadjuvant Chemotherapy. Clin Cancer Res. 2020 Jul
1;26(13):3271-3279. doi: 10.1158/1078-0432.CCR-19-3728. Epub 2020 Mar 6. PMID:
32144135; PMCID: PMC7348681.

 vi  (#_ednref6) Le DT, et al. PD-1 blockade in tumors with mismatch repair
deficiency. N Engl J Med. 2015;372(26):2509-2520.

 vii  (#_ednref7) Marabelle A, et al. Efficacy of pembrolizumab in patients
with noncolorectal high microsatellite instability/mismatch repair deficient
cancer: results from the Phase II KEYNOTE-158 study. J Clin Oncol.
2020;38(1):1-10.

 viii  (#_ednref8) National Cancer Institute at the National Institutes of
Health. Definition of mismatch repair deficiency. Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency.
Accessed May 5, 2021.

 ix  (#_ednref9) Lorenzi M, et al. Epidemiology of microsatellite instability
high (MSI-H) and deficient mismatch repair (dMMR) in solid tumors: a
structured literature review. J Oncol. 2020. doi.org/10.1155/2020/1807929.

 x  (#_ednref10) Zhao P, et al. Mismatch repair deficiency/microsatellite
instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J
Hematol Oncol. 2019;12(1):54. doi: 10.1186/s13045-019-0738-1.

(#_ednref11)

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