Ovarian Mucinous Adenocarcinoma

Observing how cells are organised in mucinous ovarian cancer can lead to new treatment options, study shows. A global study into mucinous ovarian cancer could help oncologists recommend the best treatment for women who are diagnosed early with the condition. By looking down a microscope for two different 'patterns of invasion' -- the way that cancer cells invade ovarian tissue -- oncologists can better predict which patients may have better or worse prognoses and can target treatment accordingly. The finding was reported in a paper published today in Clinical Cancer Research, a journal of the American Association for Cancer Research. "Mucinous ovarian cancer is a rare type of ovarian cancer. It actually has more in common with gastrointestinal cancers, and can be hard to diagnose and hard to treat once it has spread beyond the ovaries," says lead author Nicki Meagher, who has just completed her PhD in the Molecular Oncology group, UNSW School of Clinical Medicine. She says that observing which of the two types of invasion patterns that the cancer cells form could help specialists decide on treatment strategies. "We've shown for the first time that women who have early-stage disease -- meaning they have tumours that haven't spread beyond the ovary -- have much poorer survival chances in the first two years from diagnosis if they have what we call an infiltrative pattern of invasion. "Knowing this in the early stage of the disease means we can identify patients who could benefit from additional chemotherapy following surgery to remove their ovaries." The two patterns of invasion are defined by the way the cancer cells organise themselves when viewed under a microscope. The infiltrative pattern of invasion associated with poorer health outcomes shows cancer cells spreading in an uneven, haphazard way through the ovarian tissue. The other pattern is known as expansile, where cells expand through tissue in a more orderly manner, and is associated with better prognoses. Up until now, other studies had suggested that the infiltrative pattern of invasion was associated with poorer patient outcomes, but no study had large enough numbers of patients with early-stage cancer to reach statistical significance. But the current study, that involved more than 100 researchers in Australia, UK, Canada, Asia, Europe and the US, was able to test this hypothesis in much larger numbers by examining the tissue of 604 patients. The researchers also looked for the expression of 19 genes including THBS2 and TAGLN in addition to the patterns of invasion. Professor Susan Ramus who oversaw the global study and heads the Ovarian Tumour Tissue Analysis consortium says that guidelines on how to treat women with early-stage mucinous ovarian cancer have differed around the world due to limited data on infiltrative patterns of invasion associated with survival rates. "For example, in some parts of the world, an infiltrative pattern was acknowledged as an important feature and determined what treatment those women receive," Professor Ramus says. "Whereas in others, all patients are recommended for the same pathway of treatment. We hope that after this large study treatment guidelines can be aligned and that we can target treatment for women who may have these more serious indicators, even if they are diagnosed in early stages." The researchers also noted that women with higher expression of two genes, THBS2 and TAGLN in their tumours, had poorer overall survival. "We're hoping that this may be able to help explain some of the biology potentially down the track," says Ms Meagher. "Another avenue could be that knowledge of expression of these genes could assist in developing targeted drugs." The researchers are part of a wide network of experts who plan to carry out a validation study to further investigate these genomic markers as the basis for a targeted treatment strategy.

AnaptysBio and GSK-partnered immuno-oncology agents JEMPERLI (dostarlimab-gxly) and cobolimab show positive progress in two separate non-small cell lung cancer trials Positive headline results from PERLA, a head-to head Phase 2 trial of JEMPERLI vs. Keytruda in patients with metastatic non-squamous non-small cell lung cancer COSTAR, a Phase 2 trial of JEMPERLI plus cobolimab, an anti-TIM-3 antagonist antibody licensed to TESARO, Inc. (GSK) as part of the same collaboration agreement as JEMPERLI, achieved pre-specified efficacy and safety criteria Combination of JEMPERLI plus cobolimab to advance to Phase 3 for the treatment of advanced non-small cell lung cancer where AnaptysBio expects to receive a $5 million milestone from GSK during Q4 2022 on dosing of the first patient with cobolimab SAN DIEGO, Oct. 05, 2022 (GLOBE NEWSWIRE) -- AnaptysBio, Inc. (Nasdaq: ANAB), a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics, today announced that GSK’s study PERLA, a head-to-head trial of JEMPERLI vs. Keytruda in patients with metastatic non-squamous non-small cell lung cancer, met its primary endpoint of objective response rate (ORR) of dostarlimab plus chemotherapy versus pembrolizumab plus chemotherapy as assessed by blinded independent central review per RECIST v1.1. GSK expects to present full results from the PERLA trial, including the primary endpoint of ORR and the key secondary endpoint of progression-free survival, with results by programmed death ligand-1 (PD-L1) expression subgroups, at an upcoming scientific meeting. AnaptysBio also announced today that GSK is advancing both arms of the COSTAR Lung clinical trial from Phase 2 to Phase 3, testing both doublet and triplet combinations of dostarlimab plus chemotherapy, and cobolimab plus dostarlimab plus chemotherapy in advanced non-small cell lung cancer. This decision follows the recommendation of the trial’s Independent Data Monitoring Committee, reflecting the achievement of pre-specified efficacy and safety criteria per the COSTAR protocol. The COSTAR Lung Phase 3 trial is a randomized, open label 3-arm trial comparing cobolimab plus dostarlimab plus docetaxel to dostarlimab plus docetaxel to docetaxel alone in patients with advanced NSCLC who have progressed on prior anti-PD-(L)1 therapy and chemotherapy. AnaptysBio expects to receive a $5 million milestone payment from GSK upon dosing of the first patient with cobolimab in the Phase 3 portion of COSTAR. JEMPERLI and cobolimab were discovered at AnaptysBio and licensed to TESARO, Inc., now a part of the GSK group of companies, under a Collaboration and Exclusive License Agreement signed in March 2014. GSK is responsible for the ongoing research, development, commercialization and manufacturing of each of these monoclonal antibody therapies under the agreement. “We are encouraged to see immuno-oncology molecules discovered at Anaptys delivering differentiated outcomes and advancing on multiple fronts by GSK,” said Daniel Faga, interim president and chief executive officer of AnaptysBio. “We intend to leverage our strong capital position, which has been supported in part from the partial monetization of potential future royalty streams from this immuno-oncology portfolio, as we focus on the R&D of our novel immune cell modulator pipeline. This includes our two checkpoint agonists in clinical-stage development, rosnilimab, a PD-1 agonist, and ANB032, a BTLA-agonist, which act directly on cell types mediating disease pathology and have the potential to treat a broad range of autoimmune and inflammatory disorders.” About PERLA The PERLA phase 2 trial is a global, randomized, double-blind trial of 243 patients evaluating the efficacy and safety of dostarlimab plus chemotherapy compared to pembrolizumab plus chemotherapy in patients with metastatic non-squamous NSCLC without a known sensitizing epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, V600E mutation of the BRAF gene or other genomic mutation for which an approved targeted therapy is available. Patients were randomized 1:1 to receive either dostarlimab 500 mg intravenous (IV) or pembrolizumab 200 mg IV every three weeks in combination with chemotherapy. Patients were stratified by PD-L1 expression (TPS About COSTAR Lung The COSTAR Lung trial (NCT04655976) is a phase 2/3 global, randomized, open-label trial of 750 patients. The study evaluates the efficacy and safety of cobolimab plus dostarlimab plus docetaxel and dostarlimab plus docetaxel compared to docetaxel in patients with advanced non-squamous and squamous NSCLC whose disease had progressed on prior therapy with an anti-PD-(L)1 agent and a platinum doublet-based chemotherapy given in combination or in sequence. The study does not include patients with a known sensitizing epidermal growth factor receptor, anaplastic lymphoma kinase, or receptor tyrosine kinase-1 mutation, for which an approved targeted therapy is available. Patients are randomized 2:2:1 to receive either cobolimab 300 mg plus dostarlimab 500mg plus docetaxel 75 mg/m2 intravenous (IV) every three weeks (Q3W) or dostarlimab 500mg plus docetaxel 75 mg/m2 IV Q3W or docetaxel 75 mg/m2 IV Q3W. Patients are stratified by prior line of therapy (1 vs 2), PD-L1 expression (TPS ≥50% versus About JEMPERLI (dostarlimab-gxly) JEMPERLI is a programmed death receptor-1 (PD-1)-blocking antibody that binds to the PD-1 receptor and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2.vii JEMPERLI is being investigated in registrational enabling studies, as monotherapy and as part of combination regimens, including in women with recurrent or primary advanced endometrial cancer, women with stage III or IV non-mucinous epithelial ovarian cancer, and in patients with other advanced solid tumors or metastatic cancers. JEMPERLI is not approved anywhere in the world in combination with chemotherapy in first-line patients with metastatic non-squamous NSCLC or in combination with other agents to treat patients with advanced NSCLC who have progressed on prior anti-PD-L1 therapy and chemotherapy. About Cobolimab Cobolimab is an investigational monoclonal antibody against the inhibitory receptor, T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3), with potential immune checkpoint inhibitory and antineoplastic activities. About AnaptysBio AnaptysBio is a clinical-stage biotechnology company focused on delivering innovative immunology therapeutics. We are developing immune cell modulators, including two checkpoint agonists in clinical-stage development, for autoimmune and inflammatory disease: rosnilimab, our anti-PD-1 agonist program in Phase 2 for the treatment of moderate-to-severe alopecia areata; and ANB032, our anti-BTLA agonist program, which is broadly applicable to human inflammatory diseases associated with lymphoid and myeloid immune cell dysregulation. AnaptysBio is also developing imsidolimab, our anti-IL-36R antibody in Phase 3 for the treatment of generalized pustular psoriasis, or GPP. AnaptysBio’s antibody pipeline has been developed using our proprietary somatic hypermutation, or SHM platform, which uses in vitro SHM for antibody discovery and is designed to replicate key features of the human immune system to overcome the limitations of competing antibody discovery technologies. AnaptysBio has also developed multiple therapeutic antibodies in an immuno-oncology collaboration with GSK, including an anti-PD-1 antagonist antibody (JEMPERLI (dostarlimab-gxly) GSK4057190), an anti-TIM-3 antagonist antibody (cobolimab, GSK4069889) and an anti-LAG-3 antagonist antibody (GSK4074386). Contacts: Dennis Mulroy AnaptysBio, Inc. 858.732.0201 dmulroy@anaptysbio.com