REG - GSK PLC - Unprecedented results in Jemperli trial continue

GSKAnnouncement

03/06/2024 13:15

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RNS Number : 8876Q  GSK PLC  03 June 2024

Issued: 3 June 2024, London UK

 

Jemperli (dostarlimab) trial continues to show unprecedented results with no
evidence of disease in 100% of patients with locally advanced mismatch repair
deficient (dMMR) rectal cancer

 

·   Updated analysis from Memorial Sloan Kettering Cancer Center presented
at ASCO 2024 has expanded to 42 patients with clinical complete response

·   New treatment options are needed for patients facing negative impacts
to quality-of-life with current standard of care

 

·   Additional registrational studies of dostarlimab in dMMR/microsatellite
instability-high rectal (MSI-H) and colorectal cancer are recruiting

 

GSK plc (LSE/NYSE: GSK) today announced updated, longer-term results from the
phase II supported collaborative study with Memorial Sloan Kettering Cancer
Center (MSK) evaluating Jemperli (dostarlimab) as a first-line treatment-as an
alternative to surgery-for mismatch repair deficient (dMMR) locally advanced
rectal cancer. The trial showed an unprecedented 100% clinical complete
response rate (cCR) in 42 patients who completed treatment with dostarlimab,
defined as complete pathologic response or no evidence of tumours as
assessed by magnetic resonance imaging, endoscopy and digital rectal exam. In
the first 24 patients evaluated, a sustained clinical complete response with a
median follow-up of 26.3 months (95% CI: 12.4-50.5) was observed.

 

These late-breaking data are being presented today at the 2024 American
Society of Clinical Oncology (ASCO) Annual Meeting (31 May - 4 June) in
Chicago, IL as a rapid oral presentation (abstract LBA3512). The latest
research presented today from the phase II trial builds on the findings
initially presented in a late-breaking presentation at the 2022 ASCO Annual
Meeting with simultaneous publication in The New England Journal of
Medicine.1

 

Hesham Abdullah, Senior Vice President, Global Head Oncology, R&D, GSK,
said: "The data showing no evidence of disease in 42 patients is remarkable.
These results bring us one step closer to understanding the potential of
dostarlimab in this curative-intent setting for patients with dMMR locally
advanced rectal cancer. We look forward to evaluating dostarlimab in certain
colorectal cancers in our ongoing AZUR-1 and AZUR-2 registrational studies."

 

The current standard of care (SoC) for patients with dMMR/microsatellite
instability-high (MSI-H) locally advanced rectal cancer is initial treatment
with chemotherapy plus radiation followed by surgery to remove the tumour
along with portions of the intestine and/or surrounding tissue.1 (#_edn1) This
results in initial positive outcomes for most patients, but nearly one-third
ultimately die from cancer that has spread to other parts of the body (distant
metastasis).2 (#_edn2) Additionally, the surgery and chemoradiotherapy
associated with SoC can lead to long-term adverse effects that have a
significantly negative impact on quality of life, including bowel, urinary and
sexual dysfunction, secondary cancers and infertility.1

 

Andrea Cercek, MD, Section Head of Colorectal Cancer and Co-Director of the
Center for Young Onset Colorectal and Gastrointestinal Cancer, MSK, and
Principal Investigator of the phase II study said: "These findings demonstrate
the potential of dostarlimab as a novel approach to treating locally advanced
dMMR rectal cancer that leads to durable complete tumour regression without
the need for life-altering treatment. As a clinician, I've seen firsthand the
debilitating impact of standard treatment of dMMR rectal cancer and am
thrilled about the potential of dostarlimab in these patients."

 

The safety and tolerability profile of dostarlimab was generally consistent
with the known safety profile of the agent. No adverse events of grade 3 or
higher were reported in this trial.

 

Dostarlimab is not approved anywhere in the world for the frontline treatment
of locally advanced dMMR rectal cancer. GSK is advancing studies evaluating
dostarlimab in patients with advanced/metastatic stages of dMMR/MSI-H
colorectal cancer through its AZUR clinical trial programme. AZUR-1 is a
global, multi-centre, open-label, phase II registrational clinical trial
investigating the efficacy and safety of dostarlimab as monotherapy - as a
replacement for chemotherapy, radiation and/or surgery - for treatment-naïve
patients with dMMR/MSI-H locally advanced rectal cancer. The AZUR-1 trial aims
to confirm the findings of the supported collaborative study in locally
advanced dMMR rectal cancer led by Dr. Cercek at MSK. AZUR-2 is a phase III
trial evaluating the efficacy of perioperative dostarlimab compared with SoC
in participants with untreated T4N0 or Stage III (resectable) dMMR/MSI-H colon
cancer.

 

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.(3) Colorectal cancer is the third most commonly
diagnosed cancer in the world.(4) In the US, it is estimated that
approximately 46,220 individuals are diagnosed annually with rectal cancer.(5)
Approximately 5-10% of all rectal cancers are mismatch repair deficient
(dMMR)/microsatellite instability-high (MSI-H), meaning that they contain
abnormalities that affect the proper repair of DNA when copied in a cell.(6)
Mismatch repair deficient status is a biomarker that has been shown to predict
response to immune checkpoint blockade with PD-1 therapy.(7,8) Tumours with
this biomarker are most commonly found in endometrial, colorectal and other
gastrointestinal cancers but may also be found in other solid tumours.(9-12)

 

About Jemperli (dostarlimab)

Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, is the
backbone of GSK's ongoing immuno-oncology-based research and development
programme. A robust clinical trial programme includes studies of Jemperli
alone and in combination with other therapies in gynaecologic, colorectal and
lung cancers, as well as where there are opportunities for transformational
outcomes. It is the first and only immuno-oncology treatment approved, in
combination with chemotherapy, in the frontline setting for primary advanced
or recurrent dMMR/MSI-H endometrial cancer.

 

In the US, Jemperli is indicated in combination with carboplatin and
paclitaxel, followed by Jemperli as a single agent for the treatment of adult
patients with primary advanced or recurrent endometrial cancer that is dMMR,
as determined by a US FDA-approved test, or MSI-H, and as a single agent for
adult patients with dMMR recurrent or advanced endometrial cancer, as
determined by a US FDA-approved test, that has progressed on or following a
prior platinum-containing regimen in any setting and are not candidates for
curative surgery or radiation. The sBLA supporting this indication in
combination with carboplatin and paclitaxel for dMMR/MSI-H primary advanced or
recurrent endometrial cancer received Breakthrough Therapy designation and
Priority Review from the US FDA. Jemperli is also indicated in the US for
patients with dMMR recurrent or advanced solid tumours, as determined by a US
FDA-approved test, that have progressed on or following prior treatment and
who have no satisfactory alternative treatment options. The latter indication
is approved in the US under accelerated approval based on tumour response rate
and durability of response. Continued approval for this indication in solid
tumours may be contingent upon verification and description of clinical
benefit in a confirmatory trial(s).

 

Jemperli was discovered by AnaptysBio, Inc. and licensed to TESARO, Inc.,
under a collaboration and exclusive license agreement signed in March 2014.
Under this agreement, GSK is responsible for the ongoing research,
development, commercialisation, and manufacturing of Jemperli, and cobolimab
(GSK4069889), a TIM-3 antagonist.

 

Important Information for Jemperli in the EU

 

Indication 

 

Jemperli is indicated:

·      in combination with carboplatin-paclitaxel, for the treatment of
adult patients with mismatch repair deficient (dMMR)/microsatellite
instability-high (MSI-H) primary advanced or recurrent endometrial cancer and
who are candidates for systemic therapy;

·      as monotherapy for treating 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)
(https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli) EMA 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 here: https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli.

GSK in oncology

Oncology is an emerging therapeutic area for GSK where we are committed to
maximising patient survival with a current focus on haematologic malignancies,
gynaecologic cancers, and other solid tumours through breakthroughs in
immuno-oncology and tumour-cell targeting therapies.

 

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.

 

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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 under
Item 3.D "Risk factors" in GSK's Annual Report on Form 20-F for 2023, and
GSK's Q1 Results for 2024.

Registered in England & Wales:
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Brentford, Middlesex

TW8 9GS

 

Dr. Cercek has financial interests related to GSK.

References

1 (#_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.

2 (#_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.

(3) 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.

(4) SEER Explorer. SEER Explorer Application. Accessed April 19, 2024.
Available at https://seer.cancer.gov/statistics-network/explorer/
(https://seer.cancer.gov/statistics-network/explorer/) .

(5) Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J
Clin. 2024;74(1):12-49. Doi:10.3322/caac.21820.

(6) 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:
1158/1078-0432.CCR-19-3728. Epub 2020 Mar 6. PMID: 32144135; PMCID:
PMC7348681.

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

(8) 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.

(9) National Cancer Institute at the National Institutes of Health. Definition
of mismatch repair deficiency. Accessed April 19, 2024. Available at:
https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency
(https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency)
.

(10) 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.

(11) 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.

(12) Laken H, Kehry M, Mcneeley P, et al. Identification and characterization
of TSR-042, a novel anti-human PD-1 therapeutic antibody. European Journal of
Cancer. 2016;69, S102. doi:10.1016/s0959-8049(16)32902-1.

 

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