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DRUG:

Zynyz (retifanlimab-dlwr)

i
Other names: INCMGA0012, MGA 012, MGA012, INCMGA 0012 , INCMGA00012, ZL-1306, ZL 1306, ZL1306, MGA-012
Company:
Incyte, MacroGenics
Drug class:
PD1 inhibitor
Related drugs:
10d
INCMGA00012 in Patients With Previously Treated Unresectable or Metastatic Adenosquamous Pancreatic or Ampullary Cancer (clinicaltrials.gov)
P2, N=25, Completed, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Recruiting --> Completed | Trial completion date: Aug 2028 --> Dec 2024 | Trial primary completion date: Dec 2024 --> Aug 2024
Trial completion • Trial completion date • Trial primary completion date • Metastases
|
Zynyz (retifanlimab-dlwr)
13d
High-resolution crystal structure of PD-1 in complex with retifanlimab, the FDA-approved immune checkpoint blocking antibody for treating Merkel cell carcinoma. (PubMed, Biochem Biophys Res Commun)
The epitope of retifanlimab partially overlaps with the ligand binding site, and its binding induced unique conformations of the flexible loops within PD-1, including BC, C'D, and FG loops, thereby optimizing interactions with the antibody. A thorough analysis of its interaction with PD-1 and other FDA-approved anti-PD-1 antibodies may provide valuable insights into the rational design of enhanced therapies to regulate immune responses in cancer treatment.
FDA event • Journal • Checkpoint inhibition • Checkpoint block
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PD-1 (Programmed cell death 1)
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Zynyz (retifanlimab-dlwr)
15d
Enrollment change • Metastases
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KRAS (KRAS proto-oncogene GTPase)
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Erbitux (cetuximab) • irinotecan • Zynyz (retifanlimab-dlwr)
30d
Retifanlimab with Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma (clinicaltrials.gov)
P2, N=134, Recruiting, Academic and Community Cancer Research United | Not yet recruiting --> Recruiting
Enrollment open • Combination therapy
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Avastin (bevacizumab) • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn) • Zynyz (retifanlimab-dlwr)
2ms
PD-L1 Upregulation in Circulating Tumor Associated Cells Predicts for clinical outcomes in a phase I/II clinical trial using SV-BR-1-GM vaccine with the check point inhibitor retifanlimab in Metastatic Breast Cancer Patients, an Interim Analysis (SABCS 2024)
SV-BR-1-GM treatment includes low pre-dose cyclophosphamide, intradermal inoculation of ~20 million irradiated SV-BR-1-GM cells, post-dose local interferon-α with cycles and an anti-PD-1 inhibitor (retifanlimib), with cycles every 3 weeks. In an interim analysis of heavily treated mBC patient population, we observed that treatment with the SV-BR-1-GM regimen was associated with decreases in the presence of CTCs and CAMLs in 38% of patients, which significantly correlated with better PFS and trended for better OS within 2 years. Further, SV-BR-1-GM therapy appeared to upregulate PD-L1 in n=13 patients which appeared to have better responses to combination treatment with the anti-PD-1 check point inhibitor retifanlimab.
Clinical • Clinical data • P1/2 data • PD(L)-1 Biomarker • IO biomarker • Metastases
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PD-L1 expression
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FoundationOne® Liquid CDx
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cyclophosphamide • Zynyz (retifanlimab-dlwr) • Bria-IMT (SV-BR-1-GM)
2ms
A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201) (clinicaltrials.gov)
P2, N=107, Completed, Incyte Corporation | Active, not recruiting --> Completed
Trial completion • Metastases
|
Zynyz (retifanlimab-dlwr)
3ms
Retifanlimab With Bevacizumab and Hypofractionated Radiotherapy for the Treatment of Recurrent Glioblastoma (clinicaltrials.gov)
P2, N=134, Not yet recruiting, Academic and Community Cancer Research United | Initiation date: Apr 2024 --> Sep 2024
Trial initiation date • Combination therapy
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Avastin (bevacizumab) • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn) • Zynyz (retifanlimab-dlwr)
3ms
Enrollment closed • Enrollment change • Combination therapy • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • POLE (DNA Polymerase Epsilon)
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PD-L1 expression • MSI-H/dMMR • FGFR mutation • FGFR1 mutation
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Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr) • epacadostat (INCB024360) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
3ms
Enrollment open • Metastases
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Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr)
4ms
PD-1, LAG-3 and TIM-3 Checkpoint Blockade in DLBCL (clinicaltrials.gov)
P1, N=0, Withdrawn, University of Alabama at Birmingham | N=18 --> 0 | Not yet recruiting --> Withdrawn
Enrollment change • Trial withdrawal • CAR T-Cell Therapy • Checkpoint inhibition • Checkpoint block
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Zynyz (retifanlimab-dlwr) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
5ms
Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck (clinicaltrials.gov)
P2, N=176, Active, not recruiting, Incyte Biosciences International Sàrl | Recruiting --> Active, not recruiting | Trial completion date: Sep 2024 --> Jun 2025 | Trial primary completion date: May 2024 --> Feb 2025
Enrollment closed • Trial completion date • Trial primary completion date • Combination therapy • Metastases
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PD-L1 (Programmed death ligand 1)
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Zynyz (retifanlimab-dlwr) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
6ms
Phase Ib Trial of Multivalent Autophagosome Vaccine With or Without GITR Agonist, With Anti-PD-1 Immunotherapy in HNSCC (clinicaltrials.gov)
P1, N=56, Recruiting, Providence Health & Services | Active, not recruiting --> Recruiting | Trial completion date: Jul 2024 --> Dec 2027 | Trial primary completion date: Dec 2023 --> Dec 2025
Enrollment open • Trial completion date • Trial primary completion date • Checkpoint inhibition • Metastases
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CD4 (CD4 Molecule)
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Zynyz (retifanlimab-dlwr) • DPV-001 • ragifilimab (INCAGN1876)
6ms
POD1UM-101: A Phase 1 Study of INCMGA00012 in Patients With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=325, Completed, Incyte Corporation | Active, not recruiting --> Completed
Trial completion • Pan tumor • Metastases
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MSI (Microsatellite instability)
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Zynyz (retifanlimab-dlwr)
7ms
P1 data • Journal • Mismatch repair • Microsatellite instability
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MSI (Microsatellite instability)
|
Zynyz (retifanlimab-dlwr)
7ms
Enrollment open • Combination therapy • Metastases
|
paclitaxel • Zynyz (retifanlimab-dlwr) • Niktimvo (axatilimab-csfr)
7ms
Palbociclib and INCMGA00012 in People With Advanced Liposarcoma (clinicaltrials.gov)
P2, N=42, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed • Metastases
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Ibrance (palbociclib) • Zynyz (retifanlimab-dlwr)
7ms
Combination therapy • Trial completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
PD-L1 expression • HER-2 positive
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PD-L1 IHC 22C3 pharmDx
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Herceptin (trastuzumab) • 5-fluorouracil • capecitabine • oxaliplatin • Margenza (margetuximab-cmkb) • Zynyz (retifanlimab-dlwr) • tebotelimab (MGD013)
7ms
POD1UM-304: Platinum-Based Chemotherapy With/Without INCMGA00012, an Anti-PD-1 Antibody, in Non-Small Cell Lung Cancer (clinicaltrials.gov)
P3, N=583, Active, not recruiting, Incyte Corporation | Trial primary completion date: Jun 2024 --> Dec 2023
Trial primary completion date • Metastases
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cisplatin • carboplatin • albumin-bound paclitaxel • pemetrexed • Zynyz (retifanlimab-dlwr)
8ms
Retifanlimab (Anti-PD-1 Antibody) With Gemcitabine and Docetaxel in Patients With Advanced Soft Tissue Sarcoma (clinicaltrials.gov)
P1/2, N=67, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting
Enrollment closed • Checkpoint inhibition • Checkpoint block • Metastases
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gemcitabine • docetaxel • Zynyz (retifanlimab-dlwr)
8ms
Retifanlimab and Epacadostat in Combination With Radiation and Bevacizumab in Patients With Recurrent Gliomas (clinicaltrials.gov)
P2, N=51, Active, not recruiting, Washington University School of Medicine | Trial primary completion date: Apr 2024 --> Jul 2024
Trial primary completion date • Combination therapy
|
Avastin (bevacizumab) • Zynyz (retifanlimab-dlwr) • epacadostat (INCB024360)
8ms
New P2 trial • Metastases
|
Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr)
8ms
Merkel Cell Carcinoma: Integrating Epidemiology, Immunology, and Therapeutic Updates. (PubMed, Am J Clin Dermatol)
Starting in 2017, four programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) immune checkpoint inhibitors-avelumab, pembrolizumab, nivolumab (utilized in both neoadjuvant and adjuvant settings), and retifanlimab-have demonstrated efficacy in treating patients with disseminated MCC on the basis of prospective clinical trials. Nevertheless, while randomized studies directly comparing immune checkpoint inhibitors and chemotherapy in MCC are lacking, immunotherapy shows response rates comparable to those previously reported with chemotherapy but with more enduring responses. Notably, adjuvant nivolumab has proven superiority to the standard-of-care therapy (observation) in the adjuvant setting.
Review • Journal • PD(L)-1 Biomarker • IO biomarker
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • Bavencio (avelumab) • Zynyz (retifanlimab-dlwr)
8ms
The Purpose of the Study is to Continue to Provide Pemigatinib to Patients With Advanced Malignancies. (clinicaltrials.gov)
P2, N=10, Terminated, Incyte Corporation | Active, not recruiting --> Terminated; A business decision due to availability of commercial drug and other options for accessing study drug treatment.
Trial termination • Metastases
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Keytruda (pembrolizumab) • Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr)
9ms
NCI-2020-02940: INCMGA00012 and Pelareorep for the Treatment of Metastatic Triple Negative Breast Cancer, IRENE Study (clinicaltrials.gov)
P2, N=25, Recruiting, Mridula George, MD | Trial primary completion date: Jan 2024 --> Jun 2024
Trial primary completion date • Oncolytic virus • IO biomarker • Metastases
|
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
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PD-L1 expression • HER-2 expression • ER expression
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Irene (pyrotinib) • Zynyz (retifanlimab-dlwr) • Reolysin (pelareorep)
9ms
Atezolizumab plus modified docetaxel, cisplatin, and fluorouracil as first-line treatment for advanced anal cancer (SCARCE C17-02 PRODIGE 60): a randomised, non-comparative, phase 2 study. (PubMed, Lancet Oncol)
Despite a higher incidence of adverse events, combining atezolizumab with mDCF is feasible, with similar dose intensity in both groups, although the primary efficacy endpoint was not met. The predictive value of a PD-L1 combined positive score of 5 or greater now needs to be confirmed in future studies.
P2 data • Journal • Metastases
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PD-L1 (Programmed death ligand 1) • PD-1 (Programmed cell death 1)
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Keytruda (pembrolizumab) • Opdivo (nivolumab) • cisplatin • Tecentriq (atezolizumab) • docetaxel • 5-fluorouracil • Bavencio (avelumab) • Zynyz (retifanlimab-dlwr)
9ms
New P1/2 trial • Combination therapy • Metastases
|
paclitaxel • Zynyz (retifanlimab-dlwr) • Niktimvo (axatilimab-csfr)
9ms
Enrollment open • Metastases
|
Zynyz (retifanlimab-dlwr) • SX-682 • Anktiva (nogapendekin alfa inbakicept-pmln)
9ms
INCB106385 Alone or in Combination With Immunotherapy in Advanced Solid Tumors (clinicaltrials.gov)
P1, N=54, Completed, Incyte Corporation | Active, not recruiting --> Completed
Trial completion • Combination therapy • Metastases
|
CD8 (cluster of differentiation 8)
|
Zynyz (retifanlimab-dlwr) • INCB106385
10ms
PD-1, LAG-3 and TIM-3 Checkpoint Blockade in DLBCL (clinicaltrials.gov)
P1, N=18, Not yet recruiting, University of Alabama at Birmingham
New P1 trial • CAR T-Cell Therapy • Checkpoint inhibition • Checkpoint block
|
Zynyz (retifanlimab-dlwr) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
10ms
BRIA-ABC: Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer. (clinicaltrials.gov)
P3, N=404, Recruiting, BriaCell Therapeutics Corporation | Initiation date: Oct 2023 --> Feb 2024
Trial initiation date • Metastases
|
ER (Estrogen receptor) • PGR (Progesterone receptor)
|
HER-2 negative
|
carboplatin • capecitabine • cyclophosphamide • Halaven (eribulin mesylate) • Zynyz (retifanlimab-dlwr) • Bria-IMT (SV-BR-1-GM)
10ms
A phase II study of retifanlimab, a humanized anti-PD-1 monoclonal antibody, in patients with solid tumors (POD1UM-203). (PubMed, ESMO Open)
Retifanlimab demonstrated durable antitumor activity in patients with melanoma, NSCLC, UC, or RCC. The efficacy and safety of retifanlimab were as expected for a PD-(L)1 inhibitor. These data support further study of retifanlimab in solid tumors.
P2 data • Journal • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1)
|
PD-L1 expression
|
Zynyz (retifanlimab-dlwr)
10ms
Optimus: An Umbrella Study to Determine the Safety and Efficacy of Various Monotherapy or Combination Therapies in Neoadjuvant Urothelial Carcinoma (clinicaltrials.gov)
P2, N=30, Terminated, Incyte Corporation | Trial completion date: Jun 2024 --> Jan 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2024 --> Jan 2024; Business Decision. No safety concerns contributed to this decision.
Trial completion date • Trial termination • Trial primary completion date • Combination therapy
|
Zynyz (retifanlimab-dlwr) • epacadostat (INCB024360) • tuparstobart (INCAGN2385) • verzistobart (INCAGN2390)
11ms
The Purpose of the Study is to Continue to Provide Pemigatinib to Patients With Advanced Malignancies. (clinicaltrials.gov)
P2, N=10, Active, not recruiting, Incyte Corporation | Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024
Trial completion date • Trial primary completion date • Metastases
|
Keytruda (pembrolizumab) • Pemazyre (pemigatinib) • Zynyz (retifanlimab-dlwr)
12ms
Enrollment open • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
Erbitux (cetuximab) • Zynyz (retifanlimab-dlwr)
12ms
Trial completion date • Trial primary completion date • Combination therapy • IO biomarker
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability) • CD8 (cluster of differentiation 8) • PD-1 (Programmed cell death 1) • CD4 (CD4 Molecule) • ICOS (Inducible T Cell Costimulator)
|
temozolomide • carmustine • Zynyz (retifanlimab-dlwr)
12ms
Study of INCA 0186 in Subjects With Advanced Solid Tumors (clinicaltrials.gov)
P1, N=57, Active, not recruiting, Incyte Corporation | Trial completion date: Jan 2024 --> Jun 2025 | Trial primary completion date: Jan 2024 --> Jun 2025
Trial completion date • Trial primary completion date • Combination therapy • Metastases
|
CD8 (cluster of differentiation 8)
|
Zynyz (retifanlimab-dlwr) • INCA00186 • INCB106385
12ms
MAHOGANY: Combination Margetuximab, Retifanlimab, Tebotelimab, and Chemotherapy Phase 2/3 Trial in HER2+ Gastric/GEJ Cancer (clinicaltrials.gov)
P2/3; Trial completion date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2023 --> Mar 2024
Combination therapy • Trial completion date • Trial primary completion date • Metastases
|
PD-L1 (Programmed death ligand 1) • MSI (Microsatellite instability)
|
PD-L1 expression • HER-2 positive
|
PD-L1 IHC 22C3 pharmDx
|
Herceptin (trastuzumab) • 5-fluorouracil • capecitabine • oxaliplatin • Margenza (margetuximab-cmkb) • Zynyz (retifanlimab-dlwr) • tebotelimab (MGD013)
12ms
New P1 trial • Metastases
|
KRAS (KRAS proto-oncogene GTPase)
|
Erbitux (cetuximab) • Zynyz (retifanlimab-dlwr)
1year
A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
P1, N=84, Active, not recruiting, Incyte Corporation | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
Phase classification • Trial completion date • Trial primary completion date • Metastases
|
FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
|
MSI-H/dMMR • FLT3-ITD mutation • FLT3 wild-type • IDH wild-type
|
Zynyz (retifanlimab-dlwr) • INCB81776
1year
New P2 trial • Combination therapy
|
Avastin (bevacizumab) • Vegzelma (bevacizumab-adcd) • Avzivi (bevacizumab-tnjn) • Zynyz (retifanlimab-dlwr)
1year
A phase 1 trial of combined MEK, STAT3 and PD-1 inhibition in metastatic pancreatic ductal adenocarcinoma (PDAC). (ASCO-GI 2024)
NCT05440942 is an open-label, prospective, single-institution phase 1 trial testing the safety, preliminary efficacy, and biomarkers of response to the combination of trametinib (MEKi), ruxolitinib (JAK2/STAT3 inhibitor) and retifanlimab (PD-1 inhibitor) in patients with metastatic PDAC. These results will be correlated with clinical response to therapy to determine biomarkers of response and resistance. Clinical trial information: NCT05440942.
P1 data • PD(L)-1 Biomarker • IO biomarker • Metastases
|
JAK2 (Janus kinase 2) • CD8 (cluster of differentiation 8) • IL6 (Interleukin 6) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CD34 (CD34 molecule) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
|
Mekinist (trametinib) • Jakafi (ruxolitinib) • Zynyz (retifanlimab-dlwr)
1year
New P1/2 trial • Metastases
|
Zynyz (retifanlimab-dlwr) • SX-682 • Anktiva (nogapendekin alfa inbakicept-pmln)