EVQLLESGGG LVQPGGSLRL SCAASGFTFS SYDMSWVRQA PGKGLEWVST ISGGGSYTYY
QDSVKGRFTI SRDNSKNTLY LQMNSLRAED TAVYYCASPY YAMDYWGQGT TVTVSSASTK
GPSVFPLAPC SRSTSESTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS
LSSVVTVPSS SLGTKTYTCN VDHKPSNTKV DKRVESKYGP PCPPCPAPEF LGGPSVFLFP
PKPKDTLMIS RTPEVTCVVV DVSQEDPEVQ FNWYVDGVEV HNAKTKPREE QFNSTYRVVS
VLTVLHQDWL NGKEYKCKVS NKGLPSSIEK TISKAKGQPR EPQVYTLPPS QEEMTKNQVS
LTCLVKGFYP SDIAVEWESN GQPENNYKTT PPVLDSDGSF FLYSRLTVDK SRWQEGNVFS
CSVMHEALHN HYTQKSLSLS LGK
DIQLTQSPSF LSAYVGDRVT ITCKASQDVG TAVAWYQQKP GKAPKLLIYW ASTLHTGVPS
RFSGSGSGTE FTLTISSLQP EDFATYYCQH YSSYPWTFGQ GTKLEIKRTV AAPSVFIFPP
SDEQLKSGTA SVVCLLNNFY PREAKVQWKV DNALQSGNSQ ESVTEQDSKD STYSLSSTLT
LSKADYEKHK VYACEVTHQG LSSPVTKSFN RGEC
(Disulfide bridge: H22-H96, H130-L214, H143-H199, H222-H’222, H225-H’225, H257-H317, H363-H421, H’22-H’96, H’130-L’214, H’143-H’199, H’257-H’317, H’363-H’421, L23-L88, L134-L194, L’23-L’88, L’194-L’134)
>Heavy Chain EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKGLEWVSTISGGGSYTYY QDSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCASPYYAMDYWGQGTTVTVSSASTK GPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYS LSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFP PKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVS VLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVS LTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFS CSVMHEALHNHYTQKSLSLSLGK
>Light Chain DIQLTQSPSFLSAYVGDRVTITCKASQDVGTAVAWYQQKPGKAPKLLIYWASTLHTGVPS RFSGSGSGTEFTLTISSLQPEDFATYYCQHYSSYPWTFGQGTKLEIKRTVAAPSVFIFPP SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC
- Statement on a Nonproprietary Name Adopted by the USAN Council: Dostarlimab [Link]
Immunoglobulin G4, anti-(programmed cell death protein 1 (PDCD1)) (humanized clone ABT1 γ4-chain), disulfide with humanized clone ABT1 κ-chain, dimer
Sequence Length: 1314, 443, 443, 214, 214multichain; modified (modifications unspecified)
- TSR 042
- ANB 011
Jemperli FDA 2021/4/22 AND EMA 2021/4/21
NEW DRUG APPROVALS
The most common adverse reactions (≥20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (≥2%) were anemia and transaminases increased.
|NAME||DOSAGE||STRENGTH||ROUTE||LABELLER||MARKETING START||MARKETING END|
|Jemperli||Injection||50 mg/1mL||Intravenous||GlaxoSmithKline LLC||2021-04-22||Not applicable|
Dostarlimab is indicated for the treatment of adults with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following prior treatment with a platinum-containing regimen.
On April 22, 2021, the Food and Drug Administration granted accelerated approval to dostarlimab-gxly (Jemperli, GlaxoSmithKline LLC) for adult patients with mismatch repair deficient (dMMR) recurrent or advanced endometrial cancer, as determined by an FDA-approved test, that has progressed on or following a prior platinum-containing regimen.
Efficacy was evaluated based on cohort (A1) in GARNET Trial (NCT02715284), a multicenter, multicohort, open-label trial in patients with advanced solid tumors. The efficacy population consisted of 71 patients with dMMR recurrent or advanced endometrial cancer who progressed on or after a platinum-containing regimen. Patients received dostarlimab-gxly, 500 mg intravenously, every 3 weeks for 4 doses followed by 1,000 mg intravenously every 6 weeks.
The main efficacy endpoints were overall response rate (ORR) and duration of response (DOR), as assessed by blinded independent central review (BICR) according to RECIST 1.1. Confirmed ORR was 42.3% (95% CI: 30.6%, 54.6%). The complete response rate was 12.7% and partial response rate was 29.6%. Median DOR was not reached, with 93.3% of patients having durations ≥6 months (range: 2.6 to 22.4 months, ongoing at last assessment).
Serious adverse reactions occurred in 34% of patients receiving dostarlimab-gxly. Serious adverse reactions in >2% of patients included sepsis , acute kidney injury , urinary tract infection , abdominal pain , and pyrexia . The most common adverse reactions (≥20%) were fatigue/asthenia, nausea, diarrhea, anemia, and constipation. The most common grade 3 or 4 adverse reactions (≥2%) were anemia and transaminases increased. Immune-mediated adverse reactions can occur including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.
The recommended dostarlimab-gxly dose and schedule (doses 1 through 4) is 500 mg every 3 weeks. Subsequent dosing, beginning 3 weeks after dose 4, is 1,000 mg every 6 weeks until disease progression or unacceptable toxicity. Dostarlimab-gxly should be administered as an intravenous infusion over 30 minutes.
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).
FDA also approved the VENTANA MMR RxDx Panel as a companion diagnostic device for selecting endometrial cancer patients for treatment with dostarlimab-gxly.
This review used the Real-Time Oncology Review (RTOR) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.
This application was granted priority review, and breakthrough therapy designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Like several other available and experimental monoclonal antibodies, it is a PD-1 inhibitor. As of 2020, it is undergoing Phase I/II and Phase III clinical trials. The manufacturer, Tesaro, announced prelimary successful results from the Phase I/II GARNET study.
April 2021, Dostarlimab is approved for the treatment of recurrent or advanced endometrial cancer with deficient mismatch repair (dMMR), which are genetic anomalies abnormalities that disrupt DNA repair.
On April 22, 2021, the Food and Drug Administration granted accelerated approval to dostarlimab-gxly (Jemperli, GlaxoSmithKline LLC). Efficacy was evaluated based on cohort (A1) in GARNET Trial (NCT02715284), a multicenter, multicohort, open-label trial in patients with advanced solid tumors.
Society and culture
On 25 February 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a conditional marketing authorization for the medicinal product Jemperli, intended for the treatment of certain types of recurrent or advanced endometrial cancer. The applicant for this medicinal product is GlaxoSmithKline (Ireland) Limited.
- ^ Jump up to:a b c d e f g h i j k “FDA grants accelerated approval to dostarlimab-gxly for dMMR endometri”. U.S. Food and Drug Administration(FDA) (Press release). 22 April 2021. Retrieved 22 April 2021. This article incorporates text from this source, which is in the public domain.
- ^ Jump up to:a b c d e f g h i “Jemperli- dostarlimab injection”. DailyMed. Retrieved 28 April 2021.
- ^ Statement On A Nonproprietary Name Adopted By The USAN Council – Dostarlimab, American Medical Association.
- ^ World Health Organization (2018). “International Nonproprietary Names for Pharmaceutical Substances (INN). Proposed INN: List 119” (PDF). WHO Drug Information. 32 (2).
- ^ “FDA grants accelerated approval for GSK’s Jemperli (dostarlimab-gxly) for women with recurrent or advanced dMMR endometrial cancer” (Press release). GlaxoSmithKline. 22 April 2021. Retrieved 22 April 2021 – via PR Newswire.
- ^ Jump up to:a b Clinical trial number NCT02715284 for “A Phase 1 Dose Escalation and Cohort Expansion Study of TSR-042, an Anti-PD-1 Monoclonal Antibody, in Patients With Advanced Solid Tumors (GARNET)” at ClinicalTrials.gov
- ^ Clinical trial number NCT03981796 for “A Study of Dostarlimab (TSR-042) Plus Carboplatin-paclitaxel Versus Placebo Plus Carboplatin-paclitaxel in Patients With Recurrent or Primary Advanced Endometrial Cancer (RUBY)” at ClinicalTrials.gov
- ^ Clinical trial number NCT03602859 for “A Phase 3 Comparison of Platinum-Based Therapy With TSR-042 and Niraparib Versus Standard of Care Platinum-Based Therapy as First-Line Treatment of Stage III or IV Nonmucinous Epithelial Ovarian Cancer (FIRST)” at ClinicalTrials.gov
- ^ “Data from GARNET study indicates robust activity of dostarlimab in patients with advanced or recurrent endometrial cancer”. Tesaro (Press release). Retrieved 1 January 2020.
- ^ Scalea B (28 May 2019). “Dostarlimab Effective in Endometrial Cancer Regardless of MSI Status”. Targeted Oncology. Retrieved 1 January 2020.
- ^ “GSK Presents New Data from the GARNET Study Demonstrating Potential of Dostarlimab to Treat a Subset of Women with Recurrent or Advanced Endometrial Cancer – Drugs.com MedNews”. Drugs.com. Retrieved 29 April 2020.
- ^ “FDA Approves New Immunotherapy for Endometrial Cancer”. Medscape. Retrieved 23 April 2021.
- ^ Jump up to:a b “Jemperli: Pending EC decision”. European Medicines Agency (EMA) (Press release). 25 February 2021. Retrieved 22 April 2021.
- “Dostarlimab”. Drug Information Portal. U.S. National Library of Medicine.
- Clinical trial number NCT02715284 for “Study of TSR-042, an Anti-programmed Cell Death-1 Receptor (PD-1) Monoclonal Antibody, in Participants With Advanced Solid Tumors (GARNET)” at ClinicalTrials.gov
- Kaplon H, Muralidharan M, Schneider Z, Reichert JM: Antibodies to watch in 2020. MAbs. 2020 Jan-Dec;12(1):1703531. doi: 10.1080/19420862.2019.1703531. [Article]
- Temrikar ZH, Suryawanshi S, Meibohm B: Pharmacokinetics and Clinical Pharmacology of Monoclonal Antibodies in Pediatric Patients. Paediatr Drugs. 2020 Apr;22(2):199-216. doi: 10.1007/s40272-020-00382-7. [Article]
- Green AK, Feinberg J, Makker V: A Review of Immune Checkpoint Blockade Therapy in Endometrial Cancer. Am Soc Clin Oncol Educ Book. 2020 Mar;40:1-7. doi: 10.1200/EDBK_280503. [Article]
- Deshpande M, Romanski PA, Rosenwaks Z, Gerhardt J: Gynecological Cancers Caused by Deficient Mismatch Repair and Microsatellite Instability. Cancers (Basel). 2020 Nov 10;12(11). pii: cancers12113319. doi: 10.3390/cancers12113319. [Article]
- FDA Approved Drug Products: Jemperli (dostarlimab-gxly) for intravenous injection [Link]
- FDA News Release: FDA grants accelerated approval to dostarlimab-gxly for dMMR endometrial cancer [Link]
- Statement on a Nonproprietary Name Adopted by the USAN Council: Dostarlimab [Link]
|Other names||TSR-042, WBP-285, dostarlimab-gxly|
|License data||US DailyMed: Dostarlimab|
|ATC code||L01XC40 (WHO)|
|Legal status||US: ℞-only |
|Chemical and physical data|
|Molar mass||144325.73 g·mol−1|
/////////Dostarlimab, PEPTIDE, ANTINEOPLASTIC, CANCER, ドスタルリマブ , GSK 4057190, GSK4057190, TSR 042, TSR-042, WBP-285, FDA 2021, EU 2021