Dostarlimab Breakthrough: FDA Green-Lights JEMPERLI for Advanced Endometrial Cancer Treatment

Clinical Milestone Signals New Hope for Hard-to-Treat Cancers

The U.S. Food and Drug Administration has approved JEMPERLI (dostarlimab-gxly), a groundbreaking immunotherapy designed to combat mismatch repair deficient (dMMR) endometrial cancer. This approval marks a significant advancement in treatment options for patients with recurrent or advanced disease that has proven resistant to platinum-based chemotherapy.

Dostarlimab operates as a PD-1 antagonist antibody, a mechanism that helps unlock the body’s immune system to target cancer cells. The drug specifically addresses endometrial cancer patients whose tumors lack functional mismatch repair proteins—a biomarker indicating potential responsiveness to immunotherapy. Approval was granted under an expedited pathway (accelerated approval) based on tumor response rates and the durability of those responses, acknowledging the urgent clinical need this patient population faces.

The Science Behind the Success

The development of dostarlimab represents a collaborative achievement between multiple organizations. AnaptysBio developed the antibody using its proprietary somatic hypermutation (SHM) antibody discovery platform—a technology that has now yielded eight therapeutic candidates in clinical development. Of these eight pipeline programs, JEMPERLI becomes the first to achieve FDA authorization, validating the platform’s potential to generate clinically meaningful therapeutics.

TESARO, Inc., acquired by GSK, assumed responsibility for advancing dostarlimab through clinical development. The collaboration structure allowed AnaptysBio to maintain focus on discovery while benefiting from GSK’s development and commercialization infrastructure. This partnership model has proven productive, with dostarlimab already showing promise across multiple tumor types beyond its initial approved indication.

Financial Implications and Milestone Structure

The FDA approval triggered an immediate $20 million milestone payment to AnaptysBio. This represents the culmination of earlier regulatory achievements—the company previously received $10 million when the FDA accepted the initial application filing, and an additional $10 million when the FDA subsequently accepted an expanded application for additional solid tumors.

Future financial opportunities remain substantial. Up to $45 million in additional regulatory milestone payments are potentially available upon achieving future approvals in the United States and Europe. Beyond regulatory achievements, commercial success could generate $165 million in sales-based milestones if dostarlimab achieves specified annual revenue thresholds.

Royalty arrangements reflect tiered revenue sharing: AnaptysBio receives 8% of annual global net sales below $1 billion, escalating to 12-25% of sales exceeding that threshold. This structure incentivizes strong commercial performance while ensuring AnaptysBio benefits meaningfully from dostarlimab’s market success.

Expanding Clinical Development Pipeline

Dostarlimab’s approved indication addresses patients with dMMR recurrent or advanced endometrial cancer who have progressed on or after platinum-containing chemotherapy. However, ongoing clinical programs suggest considerably broader potential applications.

Notably, the RUBY phase III trial is evaluating dostarlimab combined with standard chemotherapy for recurrent or primary advanced endometrial cancer. Separately, the FIRST study is testing dostarlimab plus niraparib versus standard platinum therapy as first-line treatment for stage III/IV non-mucinous epithelial ovarian cancer.

Additional investigations are underway across platinum-resistant ovarian cancer, non-small cell lung cancer, multiple myeloma, and melanoma, suggesting dostarlimab may eventually address multiple cancer types and treatment settings.

Safety Profile and Clinical Considerations

Immune checkpoint inhibitors like dostarlimab activate the immune system to attack cancer, which can occasionally trigger unintended immune reactions. Patients and clinicians must remain vigilant for immune-mediated adverse events affecting any organ system.

Immune-Mediated Pneumonitis: Occurred in 1.1% of patients, with 0.9% experiencing Grade 2 severity and 0.2% Grade 3. About 80% of pneumonitis cases resolved; however, 33% of patients who resumed dostarlimab experienced recurrence.

Immune-Mediated Colitis: Developed in 1.4% of patients (0.7% Grade 3, 0.7% Grade 2). Notably, colitis did not lead to treatment discontinuation in any patient, and 50% of cases ultimately resolved.

Thyroid Disorders: Hypothyroidism occurred most frequently at 5.6% (all Grade 2), with 40% resolving. Hyperthyroidism affected 1.8% of patients, resolving in 63% of cases. Thyroiditis was rare at 0.5%.

Hepatitis: Grade 3 immune-mediated hepatitis occurred in 0.2% of patients but resolved with corticosteroid management.

Endocrine Dysfunction: Adrenal insufficiency affected 0.9% of patients, with discontinuation required in one case. Hypophysitis risk exists and requires monitoring for symptoms including headache and visual changes.

Other Considerations: Nephritis (0.5%), dermatologic reactions, and type 1 diabetes mellitus have been documented. Management typically involves corticosteroids and, in severe cases, treatment interruption or discontinuation.

Competitive Pipeline Development

GSK continues expanding its collaboration with AnaptysBio beyond dostarlimab. Two additional antibodies are in development: cobolimab (an anti-TIM-3 antagonist) and GSK4074386 (an anti-LAG-3 antagonist). The collaboration structure permits AnaptysBio to receive development and regulatory milestones for the first two indications of each candidate, with potential aggregate milestones reaching $1.1 billion.

Royalty structures for these programs differ slightly—AnaptysBio receives 4-8% of global net sales for cobolimab and GSK4074386, plus 1% on GSK’s global net sales of Zejula (niraparib), the PARP inhibitor frequently combined with dostarlimab in ongoing trials.

This expanding partnership underscores the commercial viability of immunotherapy approaches while demonstrating AnaptysBio’s ability to generate multiple clinical-stage programs from its core antibody discovery technology.