Jemperli (dostarlimab-gxly) / AnaptysBio, GSK - LARVOL DELTA

NCCN has published updates to the NCCN Guidelines and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Rectal Cancer, Version 2.2025. (NCCN)

NCCN guideline • Rectal Cancer

Pharmacovigilance study on the reporting frequency of atrial fibrillation with immune checkpoint inhibitors: insights from FDA Adverse Event Reporting System. (PubMed, Ther Adv Drug Saf) - "Cases reporting one or more ICIs (atezolizumab, avelumab, cemiplimab, dostarlimab, durvalumab, ipilimumab, nivolumab, pembrolizumab, and tremelimumab) and atrial fibrillation were selected. The anti-CTLA-4 showed a lower likelihood of reporting atrial fibrillation, while higher reporting was found with anti-PD-1 and anti-PD-L1. Further studies are needed to confirm this safety aspect."

Adverse events • Checkpoint inhibition • Journal • Atrial Fibrillation • Cardiovascular • Oncology

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Drugs & Biologics Compendium (NCCN Compendium) for Colon Cancer, Version 2.2025. (NCCN)

NCCN guideline • Colon Cancer • Microsatellite Instability

Molecular Testing and Targeted Therapies in Hepatobiliary Cancers: A Review. (PubMed, JAMA Surg) - "Moreover, multiple solid cancer tumor-agnostic therapies are approved (larotrectinib, entrectinib, and repotrectinib for NTRK fusions; selpercatinib for RET fusions; dabrafenib and trametinib combination for BRAF V600E mutations; dostarlimab or pembrolizumab for tumors with high microsatellite instability and pembrolizumab for tumor mutation burden ≥10 mutations/megabase), highlighting the need for NGS as well as ERBB2 (formerly HER2) immunohistochemistry (IHC) (with the recent approval of solid tissue-agnostic deruxtecan trastuzumab for ERBB2-positive [IHC 3+] cancer) across cancers. Tumor-agnostic and N-of-1 clinical trials have challenged traditional clinical trial paradigms and provide the foundation for truly personalized oncology for patients with these aggressive cancers. Further work is needed to determine how to leverage these novel approaches into the management of operable disease."

IO biomarker • Journal • Tumor mutational burden • Biliary Cancer • Biliary Tract Cancer • Hepatocellular Cancer • Hepatology • Microsatellite Instability • Oncology • Solid Tumor • BRAF • HER-2 • MSI • NTRK • RET • TMB

Not always perfect: Incomplete response after immunotherapy for MMR deficient rectal cancer (ASCRS 2025) - P2 | "The CheckMate 142 trial demonstrated significant response rates with nivolumab in metastatic colorectal cancers, leading to its FDA approval for dMMR/MSI-H tumors...This underscores the heterogeneity within MSI-H tumors that may be influenced by factors such as tumor microenvironment, tumor mutation burden, and potential intratumoral heterogeneity and the need for predictive biomarkers to help risk stratify patients and more individually tailor therapeutic strategies.Patient #1Magnetic resonance imaging-T2 scans of patient in case #1 before immunotherapy initiation and after 12 cycles of pembrolizumab...Patient #2Magnetic resonance imaging-T2 scans of patient in case #2 before treatment initiation and after 8 cycles of dostarlimab. Interval imaging demonstrated essentially unchanged appearance of the primary rectal tumor."

Clinical • dMMR • IO biomarker • Tumor mutational burden • Colorectal Adenocarcinoma • Colorectal Cancer • Constipation • Gastroenterology • Gastrointestinal Disorder • Genetic Disorders • Microsatellite Instability • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor • MSH2 • MSH6 • MSI • TMB

Predicted Effectiveness of First- and Second-Line Treatment Sequences in Advanced or Recurrent Endometrial Cancer (ISPOR 2025) - "OBJECTIVES: Carboplatin-paclitaxel (CARBO+PAC) with/without immunotherapy (IO) is the standard first-line (1L) treatment for patients with advanced/recurrent endometrial cancer (EC); lenvatinib plus pembrolizumab (LEN+PEM) is the standard of care following progression on prior systemic therapy without IO...1L therapies included CARBO+PAC, dostarlimab+CARBO+PAC, and PEM+CARBO+PAC... In both populations, IO+ChT followed by LEN+PEM is projected to result in the longest survival of sequences tested; CARBO+PAC followed by non-platinum ChT is least effective. Further studies are warranted to investigate the effectiveness of LEN+PEM after IO and inform treatment sequences in advanced/recurrent EC."

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor

Cabozantinib and Dostarlimab in Recurrent Gynecologic Carcinosarcoma (clinicaltrials.gov) - P1/2 | N=37 | Recruiting | Sponsor: University of Alabama at Birmingham | Trial completion date: Jan 2026 ➔ Apr 2027 | Trial primary completion date: Apr 2025 ➔ Apr 2027

Trial completion date • Trial primary completion date • Carcinosarcoma • Endometrial Cancer • Gynecologic Cancers • Oncology • Sarcoma • Solid Tumor • Uterine Cancer

Anaptys Announces First Quarter 2025 Financial Results and Provides Business Update (GlobeNewswire) - "GSK Immuno-Oncology Financial Collaboration: (i) GSK announced strong commercial performance for Jemperli ($220 million in Q1 2025 sales) with >15% quarter-over-quarter growth...; (ii) Anticipate receipt of a $75 million commercial sales milestone payment from GSK in either 2025 or 2026 once Jemperli achieves $1 billion in worldwide net sales in a calendar year; (iii) GSK anticipates top-line data in mid-2025 from COSTAR Lung Phase 3 trial in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and platinum-based chemotherapy comparing docetaxel alone to cobolimab, a TIM-3 antagonist, plus dostarlimab, a PD-1 antagonist, plus docetaxel and to dostarlimab plus docetaxel...; (iv) GSK anticipates top-line data in 2026 from AZUR-1 pivotal Phase 2 trial of dostarlimab monotherapy in patients with untreated stage II/III dMMR/MSI-H locally advanced rectal cancer."

Clinical data • dMMR • Financing • MSI-H • Sales • Microsatellite Instability • Non Small Cell Lung Cancer • Rectal Cancer

DOMENICA: dostarlimab versus chemotherapy alone in first-line MMR-deficient advanced endometrial cancer patients. (PubMed, Future Oncol) - P3 | "Randomized clinical trials have reported results supporting the addition of IO to chemotherapy (paclitaxel plus carboplatin) in the first-line setting in advanced EC patients in the global population, with high efficacy in mismatch repair deficient (MMRd) patients. Our primary endpoint will be progression-free survival. The key secondary endpoints will be overall survival, safety and quality of life [NCT05201547]."

Clinical • dMMR • Journal • Endometrial Cancer • Oncology • Solid Tumor

DOVIPA: A Phase II Study with Safety Run-In of mFOLFIRINOX, Dostarlimab, and Oral Vitamin D in Metastatic Pancreatic Cancer with Translational Research on Resistance Mechanisms (ESMO-GI 2025) - No abstract available

Clinical • Metastases • P2 data • Hepatology • Oncology • Pancreatic Cancer • Solid Tumor

OPAL: A Study to Evaluate the Efficacy and Safety of Novel Treatment Combinations in Participants With Ovarian Cancer (clinicaltrials.gov) - P2 | N=77 | Completed | Sponsor: Tesaro, Inc. | N=125 ➔ 77 | Trial completion date: Apr 2027 ➔ Mar 2025 | Trial primary completion date: Aug 2025 ➔ Jun 2024 | Active, not recruiting ➔ Completed

Enrollment change • PD(L)-1 companion diagnostic • Platinum resistant • Trial completion • Trial completion date • Trial primary completion date • Cervical Cancer • Endometrial Cancer • Oncology • Ovarian Cancer • Solid Tumor • Vaginal Cancer • Vulvar Cancer • BRCA • BRCA1 • BRCA2

“Users of the Monitored Drug Registries are hereby informed that…under the SSN reimbursement regime…JEMPERLI is indicated in combination…for the treatment of adult patients with advanced or recurrent primary endometrial cancer with mismatch repair system deficiency (dMMR)/high microsatellite instability (MSI-H) and who are candidates for systemic therapy.” [Google translation] (Italian Medicines Agency)

dMMR • MSI-H • Reimbursement • Endometrial Cancer • Microsatellite Instability • Oncology

Time to subsequent therapy in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) receiving dostarlimab plus carboplatin-paclitaxel (DOST+CP) compared with pts receiving placebo plus CP (PBO+CP) in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT03981796 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Metastases • Endometrial Cancer • Oncology • Solid Tumor

Immune checkpoint Inhibitor-Induced Autoimmune hemolytic anemia in endometrial cancer. (PubMed, Gynecol Oncol Rep) - "Here we describe a patient with stage IVB serous endometrial carcinoma who developed autoimmune hemolytic anemia (AIHA) following her second neoadjuvant cycle of carboplatin, paclitaxel, and dostarlimab. She was hospitalized, requiring multiple blood transfusions, a prolonged steroid course, and rituximab before stabilization of her anemia...This case highlights the emerging multidisciplinary challenges that arise with the use of these novel targeted therapies. As the importance of these therapies increases in gynecologic oncologic management, it will be critical for providers to be able to diagnosis and manage their unique side effects."

Checkpoint inhibition • Journal • Anemia • Autoimmune Hemolytic Anemia • Endometrial Cancer • Gynecologic Cancers • Hematological Disorders • Immunology • Oncology • Solid Tumor

PULMO-01: A Study of Roginolisib (IOA-244) in Combination With Dostarlimab With or Without Docetaxel in Metastatic Non Small-cell Lung Cancer (NSCLC) Patients (clinicaltrials.gov) - P1/2 | N=45 | Recruiting | Sponsor: iOnctura | Not yet recruiting ➔ Recruiting

Enrollment open • IO biomarker • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • IL7R

Non operative management of mismatch repair deficient tumors (AACR 2025) - "MMRd occurs broadly across solid tumors but is unknown if these findings could be extended in a tumor agnostic manner. Early stage MMRd solid tumors that were eligible for curative intent surgery were enrolled to a study of six months of neoadjuvant treatment with dostarlimab, a PD-1 blocking monoclonal antibody... In the curative setting, neoadjuvant PD-1 blockade offers the option of organ preservation for most patients with early stage MMRd malignancies regardless of tumor type."

dMMR • IO biomarker • Mismatch repair • Tumor mutational burden • Colorectal Cancer • Gynecologic Cancers • Oncology • Rectal Cancer • Solid Tumor • TMB

Safety and tolerability of dostarlimab in combination antiretroviral therapy–refractory HIV-associated Kaposi sarcoma: Preliminary results from the StarKap phase Ib trial. (ASCO 2025) - P1 | "Clinical Trial Registration Number: NCT05646082 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P1 data • Human Immunodeficiency Virus • Infectious Disease • Kaposi Sarcoma • Oncology • Sarcoma • Solid Tumor

Randomized phase II study of neoadjuvant (neoadj) anti-PD-1 dostarlimab (D) vs. D + anti-TIM-3 cobolimab (C) in high-risk resectable melanoma (mel) (NEO-MEL-T): Primary analysis. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04139902 The abstract will be released to the public on June 3, 2025 at 7:00 AM CDT"

Clinical • Late-breaking abstract • P2 data • Melanoma • Oncology • Solid Tumor

FIRST/ENGOT-OV44: A phase 3 clinical trial of dostarlimab (dost) and niraparib (nira) in first-line (1L) advanced ovarian cancer (aOC). (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT03602859 The abstract will be released to the public on June 2, 2025 at 7:00 AM CDT"

Clinical • Late-breaking abstract • Metastases • P3 data • Oncology • Ovarian Cancer • Solid Tumor

Time to quality of life (QoL) improvement or deterioration in patients (pts) with primary advanced or recurrent endometrial cancer (pA/R EC) treated with dostarlimab plus chemotherapy in the ENGOT-EN6-NSGO/GOG-3031/RUBY trial. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT03981796 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • HEOR • Metastases • Endometrial Cancer • Oncology • Solid Tumor

Cobolimab and dostarlimab in the first-line treatment of unresectable hepatoma: A multi-center, single arm, phase 2 trial. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT03680508 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • P2 data • Hepatocellular Cancer • Liver Cancer • Solid Tumor

AZUR-4, a phase 2, open label, randomized study of neoadjuvant dostarlimab plus capecitabine plus oxaliplatin (CAPEOX) versus CAPEOX alone in previously untreated T4N0 or stage III mismatch repair proficient/microsatellite stable resectable colon cancer. (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT06567782 The abstract will be released to the public on May 22, 2025 at 4:00 PM CDT"

Clinical • Mismatch repair • P2 data • pMMR • Colon Cancer • Colorectal Cancer • Oncology • Solid Tumor

Rectal stenosis after immunotherapy in a mismatch repair deficient rectal cancer. Case report and review of literature. (PubMed, Clin Transl Radiat Oncol) - "Instead of multimodality treatment with chemoradiotherapy immunotherapy with Dostarlimab was initiated...In contrast to other oncological treatments, obstructions may worsen during immunotherapy in dMMR rectal cancers. This information has to be considered when patients are consulted regarding the optimal treatment after disease."

dMMR • Journal • Mismatch repair • Colorectal Adenocarcinoma • Colorectal Cancer • Gastrointestinal Disorder • Oncology • Rectal Adenocarcinoma • Rectal Cancer • Solid Tumor

Efficacy and Safety Study of Lurbinectedin and Dostarlimab in Cancer Patients: Protocol VHIO21001 - LiDer (clinicaltrials.gov) - P1/2 | N=0 | Withdrawn | Sponsor: Vall d'Hebron Institute of Oncology | N=15 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Endometrial Cancer • Oncology • Solid Tumor

PERLA: Efficacy Comparison of Dostarlimab Plus Chemotherapy Versus Pembrolizumab Plus Chemotherapy in Participants With Metastatic Non-squamous Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov) - P2 | N=243 | Terminated | Sponsor: GlaxoSmithKline | Completed ➔ Terminated; Trial terminated by GSK for strategic reasons, after all participants completed treatment. This decision was not based on a safety concern

Trial termination • Lung Cancer • Lung Non-Small Cell Squamous Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • BRAF • EGFR • PD-L1 • ROS1