Jemperli (dostarlimab-gxly) approved in US as first and only immunotherapy for adults with MSI-H/dMMR locally advanced rectal cancer

• Approval based on AZUR-1 data showing clinically significant proportion of participants with no detectable signs of cancer one year or more after treatment

• No disease recurrences reported among responders after median follow up of more than two years

• Jemperli monotherapy could help eligible patients avoid chemotherapy, radiation and surgery
  

GSK plc (LSE/NYSE: GSK) today announced the US Food and Drug Administration (FDA) has approved Jemperli (dostarlimab-gxly) as the first and only immunotherapy for adults with stage II and III microsatellite instability-high (MSI-H)/mismatch repair deficient (dMMR) locally advanced rectal cancer under the accelerated approval pathway.

Current standard of treatment for locally advanced rectal cancer includes chemotherapy, radiation and surgery¹, but these can have lasting consequences, including bowel, urinary and sexual dysfunction, secondary cancers and infertility^2,3. For patients with MSI-H/dMMR tumors, a biomarker found in around 5-10% of rectal cancers⁴, Jemperli monotherapy could help avoid these interventions.

Tony Wood, Chief Scientific Officer, GSK, said: “Today, Jemperli becomes the first and only approved immunotherapy for adults in the US with MSI-H/dMMR locally advanced rectal cancer. For decades, treatment has relied on chemotherapy, radiation and surgery. This approval offers a new treatment approach and represents an important step towards more personalized care for these patients.”

Dr. Andrea Cercek, MD, Principal Investigator of AZUR-1, Section Head of Colorectal Cancer and Co-Director of the Center for Young Onset Colorectal and Gastrointestinal Cancer, Memorial Sloan Kettering Cancer Center, said: “The AZUR-1 results demonstrate the potential for a fundamentally different treatment approach in this biomarker-defined patient population, and today’s approval means MSI-H/dMMR patients can now access a licensed treatment tailored to the biology of their disease.”

Michael Sapienza, CEO, Colorectal Cancer Alliance, said: “People facing rectal cancer are often thinking not only about treating their disease, but also worrying about what life will look like afterwards. The possibility of avoiding chemotherapy, radiation and surgery represents a meaningful advance for patients and their families. Biomarker testing at diagnosis will be essential to identifying patients who may be eligible for this treatment and helping them understand their options.”

Approval was based on data from the phase II AZUR-1 trial. The study met its primary objective, demonstrating a clinically significant proportion of participants achieved sustained clinical complete responses at 12 months (cCR12), with data continuing to mature.

Investigator-assessed data, a clinically relevant endpoint, showed 68% of evaluable patients (98/144; 95% CI: 60%, 76%) achieved cCR12. In an exploratory analysis, 76% (110/144; 95% CI: 69%, 83%) of evaluable patients had no evidence of cancer one year or more after treatment. This includes 68% (98/144) (95% CI: 60%, 76%) of patients who reached cCR12 without surgery, plus other participants (n=12) who had their complete response confirmed through tissue analysis after surgery (pathological complete response, or pCR). No disease recurrences have been reported among responders to date, after a median follow up of more than two years.

Data on the primary objective, cCR12 assessed by Independent Central Review, continue to mature. 47% (54/116) (95% CI: 37%, 56%) of evaluable patients have achieved cCR12. An additional 38 participants who are still progressing through to 12 month follow up have already achieved a clinical complete response.

The safety profile of Jemperli was generally consistent with its established profile across solid tumors. Serious adverse reactions occurred in 20% of patients receiving Jemperli, and the most common adverse reactions were fatigue (32%), rash (22%), diarrhea (18%) and pruritus (17%). Jemperli was permanently discontinued due to adverse reactions in 3% of patients.

Full data from the AZUR-1 interim analysis will be presented at the European Society for Medical Oncology (ESMO) Congress in October 2026.

Jemperli has received FDA Fast Track and Breakthrough Therapy designations for this indication. The application was also granted Priority Review and received a National Priority Voucher, resulting in an accelerated approval ahead of the PDUFA date.

The supplemental Biologics License Application (sBLA) is being reviewed under Project Orbis, an FDA Oncology Center of Excellence initiative that enables concurrent review by international health authorities. Regulatory reviews are ongoing in participating countries.

About stage II/III MSI-H/dMMR locally advanced rectal cancer

Around 5–10% of rectal cancers are microsatellite instability-high (MSI-H) or mismatch repair-deficient (dMMR)⁴. These tumors have a specific genetic characteristic where they are unable to properly repair DNA damage, leading to an accumulation of mutations. This unique biological feature often makes them highly responsive to immunotherapies like dostarlimab-gxly^5,6. These biomarkers are commonly found in colorectal, endometrial and other gastrointestinal cancers, but can also be present in other solid tumors⁷.

About AZUR-1

AZUR-1 is a global, open-label, single-arm, registrational phase II trial evaluating dostarlimab-gxly monotherapy in patients (n=154) with previously untreated stage II and III MSI-H/dMMR locally advanced rectal cancer. The trial was designed to assess clinical complete responses sustained for 12 months (cCR12) as determined by Independent Central Review, and to determine whether dostarlimab-gxly alone could enable patients to avoid chemotherapy, radiation and surgery. Additional efficacy outcomes include cCR12 based on investigator assessment and objective response rate (ORR), defined as patients who achieved cCR, clinical near-complete response, or clinical partial response as their best overall response. Patients received nine cycles of dostarlimab-gxly over six months, administered as a 500mg intravenous infusion every three weeks. The safety and tolerability profile of dostarlimab-gxly was generally consistent with its well-characterized safety profile observed across solid tumors. Serious adverse reactions occurred in 20% of patients receiving Jemperli and treatment was permanently discontinued due to adverse reactions in 3% of patients. The most common adverse reactions (≥15%) were fatigue, rash, diarrhea and pruritus.

About Jemperli (dostarlimab-gxly)

Jemperli, a programmed death receptor-1 (PD-1)-blocking antibody, plays an important role in GSK’s immune-oncology research and development program. A robust clinical trial program includes studies of Jemperli alone and in combination with other therapies in gynecologic, colorectal, and head and neck cancers, as well as where there are opportunities for transformational outcomes.

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, commercialization and manufacturing of Jemperli.

More information about the product and its currently approved indications is available at EU product information⁸ and US product information⁹.

Indications and Important Safety Information for JEMPERLI (dostarlimab-gxly)

• JEMPERLI, in combination with carboplatin and paclitaxel, followed by JEMPERLI as a single agent, is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer (EC).

• JEMPERLI, as a single agent, is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced:

  • EC, as determined by an FDA-authorized test, that has progressed on or following prior treatment with a platinum-containing regimen in any setting and are not candidates for curative surgery or radiation, or

  • solid tumors, as determined by an FDA-authorized test, that have progressed on or following prior treatment and who have no satisfactory alternative treatment options. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

• JEMPERLI, as a single agent, is indicated for the treatment of adult patients with Stage II/III, locally advanced rectal cancer (LARC) that is microsatellite instability-high (MSI-H) or dMMR, as determined by an FDA-authorized test for solid tumors. This indication is approved under accelerated approval based on sustained clinical complete response for 12 months. The long-term risk of relapse is unknown, with additional follow-up expected. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

Severe and Fatal Immune-Mediated Adverse Reactions

• Immune-mediated adverse reactions, which can be severe or fatal, can occur in any organ system or tissue and can occur at any time during or after treatment with a PD-1/PD-L1–blocking antibody, including JEMPERLI.

• Monitor closely for signs and symptoms of immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function tests at baseline and periodically during treatment. For suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

• Based on the severity of the adverse reaction, withhold or permanently discontinue JEMPERLI. In general, if JEMPERLI requires interruption or discontinuation, administer systemic corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) until improvement to ≤Grade 1. Upon improvement to ≤Grade 1, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reaction is not controlled with corticosteroids.

Immune-Mediated Pneumonitis

• JEMPERLI can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Pneumonitis occurred in 2% (15/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (1.2%), Grade 3 (0.7%), and Grade 4 (0.1%) pneumonitis.

Immune-Mediated Colitis

• Colitis occurred in 1.2% (9/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (0.7%) and Grade 3 (0.5%) adverse reactions. Cytomegalovirus infection/reactivation have occurred in patients with corticosteroid-refractory immune-mediated colitis. In such cases, consider repeating infectious workup to exclude alternative etiologies.

Immune-Mediated Hepatitis

• JEMPERLI can cause immune-mediated hepatitis, which can be fatal. Grade 3 hepatitis occurred in 0.5% (4/759) of patients receiving JEMPERLI as a single agent.

Immune-Mediated Endocrinopathies

• Adrenal Insufficiency

  • Adrenal insufficiency occurred in 1.1% (8/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (0.4%) and Grade 3 (0.7%). For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment per institutional guidelines, including hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

• Hypophysitis

  • JEMPERLI can cause immune-mediated hypophysitis. Grade 3 hypophysitis occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypophysitis occurred in 0.3% (2/759) of patients receiving JEMPERLI as a single agent. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

• Thyroid Disorders

  • Grade 2 thyroiditis occurred in 0.4% (3/759) of patients receiving JEMPERLI as a single agent. Grade 2 hypothyroidism occurred in 12% (30/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 2 hypothyroidism occurred in 8% (58/759) of patients receiving JEMPERLI as a single agent. Hyperthyroidism occurred in 3.3% (8/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel, including Grade 2 (2.9%) and Grade 3 (0.4%). Hyperthyroidism occurred in 2.2% (17/759) of patients receiving JEMPERLI as a single agent, including Grade 2 (2.1%) and Grade 3 (0.1%). Initiate thyroid hormone replacement or medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

• Type 1 Diabetes Mellitus, Which Can Present with Diabetic Ketoacidosis

  • JEMPERLI can cause type 1 diabetes mellitus, which can present with diabetic ketoacidosis. Grade 3 type 1 diabetes mellitus occurred in 0.4% (1/241) of patients receiving JEMPERLI in combination with carboplatin and paclitaxel. Grade 3 type 1 diabetes mellitus occurred in 0.1% (1/759) of patients receiving JEMPERLI as a single agent. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue JEMPERLI depending on severity.

Immune-Mediated Nephritis with Renal Dysfunction  

• JEMPERLI can cause immune-mediated nephritis, which can be fatal. Grade 2 nephritis, including tubulointerstitial nephritis, occurred in 0.4% (3/759) of patients receiving JEMPERLI as a single agent.

Immune-Mediated Dermatologic Adverse Reactions

• JEMPERLI can cause immune-mediated rash or dermatitis. Bullous and exfoliative dermatitis, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug rash with eosinophilia and systemic symptoms (DRESS), have occurred with PD-1/PD-L1–blocking antibodies. One patient receiving JEMPERLI experienced Grade 3 SJS, which resolved. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-bullous/exfoliative rashes. Withhold or permanently discontinue JEMPERLI depending on severity.

Other Immune-Mediated Adverse Reactions

• The following clinically significant immune-mediated adverse reactions occurred in <1% of the 759 patients treated with JEMPERLI or were reported with the use of other PD-1/PD-L1–blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

  • Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis, Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy

  • Cardiac/Vascular: Myocarditis, pericarditis, vasculitis

  • Ocular: Uveitis, iritis, other ocular inflammatory toxicities. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur

  • Gastrointestinal: Pancreatitis, including increases in serum amylase and lipase levels, gastritis, duodenitis

  • Musculoskeletal and Connective Tissue: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica

  • Endocrine: Hypoparathyroidism

  • Hematologic/Immune: Autoimmune hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection

  • Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reported as the co-occurrence of either two or all three adverse reactions.

Infusion-Related Reactions

• Severe or life-threatening infusion-related reactions have been reported with PD-1/PD-L1–blocking antibodies. Severe infusion-related reactions (Grade 3) occurred in 0.1% (1/759) of patients receiving JEMPERLI as a single agent. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion or permanently discontinue JEMPERLI based on severity of reaction.

Complications of Allogeneic HSCT

• Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after treatment with a PD-1/PD-L1–blocking antibody, which may occur despite intervening therapy. Monitor patients closely for transplant-related complications and intervene promptly.

Embryo-Fetal Toxicity and Lactation

• Based on its mechanism of action, JEMPERLI can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise women of reproductive potential to use effective contraception during treatment with JEMPERLI and for 4 months after their last dose. Because of the potential for serious adverse reactions from JEMPERLI in a breastfed child, advise women not to breastfeed during treatment with JEMPERLI and for 4 months after their last dose.

Common Adverse Reactions

The most common adverse reactions (≥20%), including laboratory abnormalities, in patients with EC who received JEMPERLI in combination with carboplatin and paclitaxel were decreased hemoglobin, increased creatinine, peripheral neuropathy, decreased white blood cell count, fatigue, nausea, alopecia, decreased platelets, increased glucose, decreased lymphocytes, decreased magnesium, decreased neutrophils, increased AST, arthralgia, rash, constipation, diarrhea, increased ALT, decreased potassium, decreased albumin, decreased sodium, increased alkaline phosphatase, abdominal pain, dyspnea, decreased appetite, increased amylase, decreased phosphate, urinary tract infection, and vomiting.

The most common adverse reactions (≥20%) in patients with dMMR EC who received JEMPERLI as a single agent were fatigue/asthenia, anemia, nausea, diarrhea, constipation, vomiting, and rash. The most common Grade 3 or 4 laboratory abnormalities (>2%) were decreased lymphocytes, decreased sodium, increased alanine aminotransferase, increased creatinine, decreased neutrophils, decreased albumin, and increased alkaline phosphatase.

The most common adverse reactions (≥20%) in patients with dMMR solid tumors who received JEMPERLI as a single agent were fatigue/asthenia, anemia, diarrhea, and nausea. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased sodium, increased alkaline phosphatase, and decreased albumin.

The most common adverse reactions (≥15%) in patients with MSI-H/dMMR LARC who received JEMPERLI as a single agent were fatigue, rash, diarrhea, and pruritus. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased lymphocytes, decreased hemoglobin, and increased AST.

Please see full Prescribing Information, including Medication Guide.

GSK in oncology

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About GSK

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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 “Risk Factors” section in GSK’s Annual Report on Form 20-F for 2025, and GSK’s Q2 Results for 2026.

References

1. 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. Negro, S. et al. (2025) ‘Quality of life in rectal cancer treatments: a systematic review’, Cancers, 17(14), 2310. Available at: https://www.mdpi.com/2072-6694/17/14/2310

3. Neibart, S.S. et al. (2020) ‘Quality of life after radiotherapy for rectal cancer’, Current Colorectal Cancer Reports, 16(1), pp. 1–10. Available at: https://pmc.ncbi.nlm.nih.gov/articles/PMC7336840/

4. 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.

5. Andre T, Berton D, Curigliano G, et al. Antitumor Activity and Safety of Dostarlimab Monotherapy in Patients With Mismatch Repair Deficient Solid Tumors: A Nonrandomized Controlled Trial. JAMA Netw Open. 2023;6(11):e2341165. doi:10.1001/jamanetworkopen.2023.41165.

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

7. National Cancer Institute at the National Institutes of Health. Definition of mismatch repair deficiency. Accessed September 2026. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/mismatch-repair-deficiency

8. JEMPERLI (dostarlimab) Summary of Product Characteristics. GlaxoSmithKline (Ireland) Limited. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/jemperli. Accessed October 2026.

9. JEMPERLI (dostarlimab-gxly) prescribing information. GlaxoSmithKline. Available at: https://gskpro.com/en-us/products/jemperli/. Accessed October 2026.

Memorial Sloan Kettering Cancer Center Disclosure: Dr Cercek has financial interests related to GSK.