Dostarlimab
- Generic Name
- Dostarlimab
- Brand Names
- Jemperli
- Drug Type
- Biotech
- CAS Number
- 2022215-59-2
- Unique Ingredient Identifier
- P0GVQ9A4S5
- Background
Dostarlimab is an IgG humanized monoclonal antibody targeted against the human programmed death receptor-1 (PD-1). PD-1 receptors are found on T-cells and, when activated, serve to inhibit immune responses - some cancers leverage this system by overexpressing PD-1 ligands, thereby effectively inhibiting the anti-tumor immune response that would typically attempt to destroy the cancerous cells. Agents acting on the PD-1 pathway, such as nivolumab and pembrolizumab, facilitate endogenous immune-mediated anti-tumor activity and may therefore be used to treat a wide variety of cancers, including those of the skin, lung, kidneys, and liver.
In April 2021, dostarlimab was granted accelerated approval by the FDA - as GlaxoSmithKline's dostarlimab-gxly (Jemperli) - for the treatment of adult patients with recurrent or advanced mismatch repair deficient (dMMR) endometrial cancer experiencing disease progression despite treatment with platinum-containing chemotherapy regimens. A companion diagnostic device - the VENTANA MMR RxDx Panel - was also approved alongside this indication to select appropriate patients for treatment. This indication was granted full FDA approval on February 10, 2023. Dostarlimab-gxly was granted second accelerated approval for the treatment of solid tumours in the same month.
Dostarlimab is currently under investigation for the treatment of rectal cancers with mismatch repair deficiency. A prospective phase II study in patients with mismatch repair-deficient locally advanced rectal cancer resulted in all twelve patients exhibiting a complete clinical response.
- Indication
Dostarlimab-gxly is indicated for the treatment of adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer that has progressed despite ongoing or prior treatment with a platinum-containing chemotherapy regimen.
It is also indicated for the treatment of solid tumours in adults, as determined by an FDA-approved test, that have progressed on or following prior treatment and in patients who have no satisfactory alternative treatment options. This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of and description of clinical benefit in confirmatory trials.
- Associated Conditions
- Advanced Microsatellite Instability High Endometrial Carcinoma, Advanced Mismatch Repair-deficient (dMMR) Endometrial Cancer, Advanced Mismatch repair deficient (dMMR) solid tumors, Recurrent Microsatellite Instability (MSI)-High Endometrial Cancer, Recurrent Mismatch Repair-deficient (dMMR) Endometrial Cancer, Recurrent Mismatch repair deficient (dMMR) solid tumors
GSK and iTeos Terminate TIGIT Cancer Drug Development After Phase 2 Failure
• GSK and iTeos Therapeutics have discontinued development of belrestotug, their TIGIT-targeting immunotherapy, after it failed to significantly delay tumor progression in non-small cell lung cancer patients.
• The companies are terminating all ongoing trials, including a Phase 3 study, ending their four-year collaboration that began with GSK's $625 million upfront payment and potential $1.45 billion in milestone payments.
• iTeos is now conducting a strategic review to preserve capital, as the failure eliminates its most advanced drug candidate and represents another setback for TIGIT-targeting therapies in oncology.
GSK's Linerixibat Shows Significant Improvement in Cholestatic Pruritus for Primary Biliary Cholangitis Patients
• GSK's phase III GLISTEN trial demonstrates linerixibat significantly improves cholestatic pruritus (relentless itch) in patients with primary biliary cholangitis, addressing a major quality of life concern.
• The late-breaking results were presented at the European Association for the Study of the Liver (EASL) Congress 2025, highlighting the potential for a new treatment option for this challenging symptom.
• Primary biliary cholangitis is a chronic autoimmune liver disease that primarily affects women, with pruritus being one of the most debilitating symptoms impacting daily functioning and quality of life.
Cancer Vaccines Emerge as Promising Frontier in Oncology with Multiple Approaches Showing Clinical Success
• Cancer vaccines are gaining momentum across multiple tumor types, with FDA-approved options like BCG, sipuleucel-T, and talimogene laherparepvec demonstrating clinical utility in bladder cancer, prostate cancer, and melanoma respectively.
• Novel vaccine approaches including mRNA-based mRNA-4157, KRAS-targeted ELI-002, and viral vector-based aglatimagene besadenovec are showing promising results in clinical trials, with significant improvements in survival outcomes across various cancers.
• Experts believe cancer vaccines hold particular promise in early-stage and high-risk disease settings by targeting micrometastatic disease, potentially increasing cure rates and transforming treatment paradigms when combined with existing immunotherapies.
Immunotherapy Alone Successfully Treats Multiple Cancer Types with MMRd Mutation, Eliminating Need for Surgery
• A groundbreaking clinical trial led by Memorial Sloan Kettering Cancer Center found that immunotherapy alone successfully treated nearly 80% of patients with various cancers carrying the MMRd genetic mutation, allowing them to avoid surgery, radiation, and chemotherapy.
• The expanded trial included 103 patients with stage 1-3 cancers including rectal, gastric, colon, esophageal, and urothelial cancers, with 100% of rectal cancer patients and 65% of patients with other cancers experiencing complete clinical responses.
• This organ-preserving approach significantly improves quality of life by maintaining fertility and normal bodily functions, with the FDA granting "Breakthrough Therapy Designation" to the checkpoint inhibitor dostarlimab for MMRd rectal cancer treatment.
Dostarlimab Shows Promise in Eliminating Need for Surgery Across Multiple dMMR Cancer Types
• Phase 2 trial results reveal dostarlimab (Jemperli) induced complete clinical responses in 100% of rectal cancer patients and 65% of non-rectal cancer patients with mismatch repair-deficient tumors, allowing 82 of 84 responders to avoid surgery.
• The groundbreaking study demonstrated 92% recurrence-free survival at two years, with some patients maintaining complete responses for up to five years, potentially transforming treatment approaches for dMMR cancers.
• Researchers highlight the significant quality-of-life benefits of avoiding surgical resection, particularly important for younger patients facing colorectal cancer diagnoses, as surgery can be debilitating and financially burdensome.
AACR Annual Meeting 2025 to Bridge Gap Between Cancer Science and Clinical Practice
• The American Association for Cancer Research (AACR) Annual Meeting 2025 in Chicago will focus on "Unifying Cancer Science and Medicine" with presentations spanning from basic research to practice-changing clinical trials.
• Program chairs Dr. Lillian Siu and Dr. Matthew Vander Heiden emphasize cross-disciplinary collaboration, encouraging attendees to explore topics outside their expertise to foster innovation in cancer research.
• Key clinical trials to be presented include promising data on zongertinib for HER2-mutant lung cancer, dostarlimab for rectal cancer, and an off-the-shelf CAR NK cell therapy for hematologic malignancies.
BeiGene Discontinues Ociperlimab Development After Failed Phase III Lung Cancer Trial
• BeiGene has terminated development of its anti-TIGIT antibody ociperlimab following a futility analysis showing the drug was unlikely to meet overall survival endpoints in non-small cell lung cancer.
• The decision comes after Novartis ended its $300 million licensing partnership with BeiGene in July 2023, forcing the biotech to reevaluate the drug's development pathway.
• This setback adds to mounting challenges in the TIGIT inhibitor space, following Merck's recent discontinuation of two Phase III trials of its anti-TIGIT candidate vibostolimab due to safety and efficacy concerns.
Northwestern's Lurie Cancer Center Joins Clinical Trial Testing LIXTE's LB-100 Plus Dostarlimab for Ovarian Clear Cell Cancer
• Northwestern University's Lurie Cancer Center has been added as the second site in LIXTE Biotechnology's clinical trial combining LB-100 with GSK's dostarlimab for ovarian clear cell cancer treatment.
• The first patient has been successfully dosed at Lurie Cancer Center under the leadership of Dr. Emily M. Hinchcliff, marking an important expansion of the study initially launched at MD Anderson Cancer Center.
• The trial aims to evaluate whether LIXTE's proprietary PP2A inhibitor LB-100 can enhance immunotherapy effectiveness in treating ovarian clear cell carcinoma, addressing a significant unmet medical need.
Tezepelumab Shows Remarkable 92% Reduction in Nasal Polyp Surgery Need in Phase 3 Trial
• Phase 3 WAYPOINT trial demonstrates tezepelumab significantly reduced nasal polyp severity and improved nasal congestion scores in patients with severe chronic rhinosinusitis with nasal polyps.
• The study showed a dramatic 92% reduction in the need for nasal polyp surgery or systemic corticosteroid treatment compared to placebo over 52 weeks.
• Patients receiving tezepelumab experienced significant improvements in multiple symptoms, including loss of smell and sino-nasal outcomes, with similar adverse event rates to placebo.
FDA Grants Priority Review to Boehringer's Zongertinib for HER2-Mutant Advanced Lung Cancer
• Boehringer Ingelheim's zongertinib could become the first oral targeted therapy for previously treated HER2-mutant advanced non-small cell lung cancer, with FDA decision expected in Q3 2025.
• Phase Ib trial demonstrated impressive 71% objective response rate in 75 previously treated NSCLC patients, with favorable safety profile and low treatment discontinuation rate.
• The drug addresses a significant unmet need in HER2-mutant NSCLC patients, who currently face poor prognosis with limited treatment options and less than 30% five-year survival rate.
GSK's Portfolio Resilience: Cancer and HIV Gains Offset RSV Vaccine Decline
• GSK experienced a significant 51% decline in Arexvy RSV vaccine sales to £590 million in 2024, following restricted US recommendations limiting use to adults 75 and older.
• Strong performance in oncology with 72% sales growth to £408 million, driven by Jemperli and Ojjaara, while HIV portfolio showed double-digit growth through Cabenuva, Apretude, and Dovato.
• Despite vaccine challenges, GSK upgraded its long-term sales forecast to £40 billion by 2031, supported by pipeline progress and planned launches in respiratory, oncology, and infectious diseases.
European Commission Approves GSK's Jemperli Plus Chemotherapy for Advanced Endometrial Cancer
• The European Commission has approved Jemperli (dostarlimab) in combination with chemotherapy for first-line treatment of advanced or recurrent endometrial cancer.
• The approval expands the indication to include patients with mismatch repair proficient/microsatellite stable (MMRp/MSS) tumors, representing approximately 75% of cases.
• The RUBY trial demonstrated a 31% reduction in the risk of death with Jemperli plus chemotherapy compared to chemotherapy alone, with a median OS of 44.6 months.
• Jemperli, a PD-1 blocking antibody, is now an approved immuno-oncology-based treatment option for all patients with advanced endometrial cancer in the EU.
Experts Address Key Challenges in Implementation of Tumor-Agnostic Therapies and Genetic Testing
• The increasing adoption of tumor-agnostic therapies has highlighted the need for universal genetic testing in oncology practices, with eight drugs now holding FDA pan-tumor approvals as of January 2025.
• Healthcare providers face complex decisions regarding genetic testing methodologies, including choices between tissue and liquid biopsies, timing of collection, and interpretation of results.
• Clinical implementation challenges include establishing efficient testing workflows, securing genetic counseling resources, and determining appropriate treatment sequencing in cases with limited tumor-specific data.
Arvinas Advances Vepdegestrant into Phase 3 Trials for Breast Cancer and Updates Pipeline Milestones
• Arvinas plans to initiate two Phase 3 trials in 2025 for vepdegestrant in ER+/HER2- metastatic breast cancer, one in the first-line setting with atirmociclib and another in the second-line setting with a CDK4/6 inhibitor.
• Topline data from the Phase 3 VERITAC-2 monotherapy trial of vepdegestrant in second-line-plus ER+/HER2- metastatic breast cancer is anticipated in the first quarter of 2025.
• Arvinas is set to present initial data from the Phase 1 trial of ARV-393 in B-cell lymphomas and file an IND application for a novel PROTAC KRAS G12D degrader in 2025.
• Phase 1 trial with PROTAC LRRK2 degrader ARV-102 in patients with Parkinson’s disease has been initiated, with data expected to be presented in the first half of 2025.
FDA Approvals in 2024: Advancing Treatment Paradigms in Solid Tumors and Hematologic Malignancies
• The FDA granted over 65 approvals in 2024, significantly impacting treatment paradigms across various cancers, including breast, gynecologic, skin, and genitourinary malignancies.
• Several tumor-agnostic approvals, such as fam-trastuzumab deruxtecan-nxki (Enhertu) for HER2-positive solid tumors and repotrectinib (Augtyro) for NTRK fusion-positive tumors, marked advancements in precision medicine.
• Immunotherapies like nivolumab (Opdivo) and pembrolizumab (Keytruda) received multiple approvals, including combinations with chemotherapy for urothelial and endometrial carcinomas, improving patient outcomes.
• Targeted therapies like vorasidenib (Voranigo) for low-grade glioma and selpercatinib (Retevmo) for RET-mutated thyroid cancers addressed unmet needs and demonstrated high efficacy and tolerability.
BioNTech's Bispecific Antibody BNT-327 Shows Promise in Triple-Negative Breast Cancer
• BioNTech's BNT-327, a bispecific antibody targeting PD-L1 and VEGF, has demonstrated positive early results in patients with triple-negative breast cancer.
• The bispecific antibody builds on the success of checkpoint inhibitors like Keytruda, potentially representing the next generation of immunotherapy drugs.
• Early trial data, presented at the San Antonio Breast Cancer Symposium, suggest BNT-327 could become a critical component in treating triple-negative breast cancer.
• The development of BNT-327 aligns with a broader interest in PD1/PD-L1 and anti-VEGF bispecifics, following promising results from Summit Therapeutics in lung cancer.
Keytruda/Lenvima Combo Shows Mixed Results in Gastroesophageal Adenocarcinoma Trial
• The Phase 3 LEAP-015 trial evaluated Keytruda plus Lenvima with chemotherapy for HER2-negative gastroesophageal adenocarcinoma.
• The combination significantly improved progression-free survival and objective response rate compared to chemotherapy alone.
• However, the trial failed to meet its other primary endpoint of overall survival in the final analysis.
• The safety profile of the Keytruda plus Lenvima regimen was consistent with prior studies.
GSK's Nucala (Mepolizumab) Shows Promise in COPD Treatment, Regulatory Submissions Underway
• GSK's Nucala (mepolizumab) demonstrates a clinically meaningful reduction in moderate/severe exacerbations in COPD patients with an eosinophilic phenotype.
• The MATINEE Phase III trial supports regulatory submissions for Nucala as an add-on maintenance treatment for COPD, potentially the first monthly biologic for this condition.
• Regulatory reviews are underway in both the US (FDA) and China (CNMPA), with the US PDUFA date set for May 7, 2025.
• Nucala, already approved for other IL-5 mediated conditions, could offer a targeted therapy for up to 40% of COPD patients with type 2 inflammation.
Immunotherapy Plus Chemotherapy Redefines Frontline Treatment for Advanced Endometrial Cancer
• Immunotherapy combined with chemotherapy is now a standard frontline treatment for advanced endometrial cancer, showing significant benefits for most patients.
• Dostarlimab-gxly and pembrolizumab, both combined with chemotherapy, have received FDA approval for primary advanced or recurrent endometrial cancer, impacting treatment paradigms.
• Updated overall survival data from the RUBY trial demonstrated a clinically significant 7-month difference in OS for pMMR patients treated with dostarlimab plus chemotherapy compared to placebo.
• Patient selection is crucial, with NCCN guidelines and inclusion criteria from KEYNOTE-868 and RUBY trials influencing insurance approvals for pembrolizumab versus dostarlimab.
GSK and iTeos' Belrestotug Shows Promise in NSCLC Trial, Offering Hope for TIGIT Therapies
• Belrestotug, an anti-TIGIT antibody from GSK and iTeos, demonstrated a higher objective response rate (ORR) when combined with GSK's Jemperli (dostarlimab) in PD-L1-positive NSCLC patients.
• The GALAXIES Lung-02 phase 2 trial showed a dose-response relationship with belrestotug, with the highest dose achieving a 76.7% ORR compared to 28.1% for Jemperli alone.
• While side effects were generally manageable, the combination therapy had higher treatment discontinuation rates and some treatment-related deaths, warranting careful safety monitoring.
• A phase 3 trial, GALAXIES-Lung-301, is planned using the 400mg dose of belrestotug in combination with Jemperli, comparing it to Keytruda plus placebo in first-line NSCLC patients.
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