ORR up to 32%! The results of the new CXCR4 antagonist joint keytruda pancreatic cancer IIa phase were released.

BioLineRx, a biopharmaceutical company focused on oncology drug development, announced that the results of the IIa BATTLE/BASE-202 study, which evaluates the lead drug CXCR4 antagonist motixafortide (BL-8040), and Keytruda and chemotherapy, are published in the prestigious medical journal Nature Medicine.
PD-1 inhibitors have limited therapeutic effect in pancreatic catheter adenocarcinoma (PDAC), highlighting the need to simultaneously target alternative pathways.
in the PDAC mouse model, blocking CXC chemofactor receptor 4 (CXCR4) promotes T-cell tumor immersion and synergies with anti-PD-1 therapy.
COMBAT/KEYNOTE-202 is an open-label, two-group II study designed to assess the safety, efficacy and immunobiological effects of the motixafortide joint Keytruda and chemotherapy treatment metastatic PDAC.
the primary endpoint is objective mitigation rate (ORR), and the secondary endpoint is total lifetime (OS), disease control rate (DCR), and safety.
the first queue in 37 patients who were difficult to treat with 1-4 previous chemotherapy regimens, and evaluated the combination of motixafortide and Keytruda.
data show that of the 29 assessable patients, DCR was 34.5%, of which 9 cases were stable, 1 was partially remissioned, and mOS was 3.3 months.
noteworthy, the second-line patients (n-6) had 7.5 months of mOS.
in addition, motixafortide monodrug therapy, motixafortide and Keytruda combination therapy showed increased dysplion in CD8-effect T-cell tumor immersion, reduction of myelin-induced inhibitory cells in tumor microenvironments, and reduction in circulating immunosuppressive dendritic cells, all of which confirmed the initial hypothesis and the mechanisms previously observed in animal models.
dual combination therapy (pictured: published) initiated a second study queue based on data on the clinical and immunobiological effects observed in the first queue, as well as the increased anti-tumor effects of chemotherapy combined motixafortide and PD-1 inhibitors observed in preclinical studies, incorporating the tri-drug programme (motixfortide and Keytruda plus chemotherapy).
the second cohort program includes 40 patients who were diagnosed with metastatic PDAC at the time of their initial diagnosis and progressed after receiving first-line chixiata treatment.
the entry completed in January 2020, the mid-year report is no progression survival (PFS) and OS data.
at the time of submission, preliminary data from 22 patients in the queue were available, with data showing ANR of 32%, DCR at 77% and median clinical benefit duration of 7.8 months.
these data show therapeutic progress compared to the standard chemotherapy care currently used for second-line therapy (ORR s 17%, DCR x 52%, median clinical benefit duration of 3 months).
triple combination therapy (pictured: article) PDAC is one of the most difficult to treat because it is usually late at the time of initial diagnosis and has a relative lying chemotherapy resistance and a highly immune repressive microenvironment, and is therefore considered the most "cold" tumor.
Although immunotherapy (e.g. checkpoint inhibitors) has a positive effect on prognosis in many other types of cancer patients, PDAC has a poor response to immunotherapy treatment for these reasons.
published this article, describing the combination of motixafortide and Keytruda showing encouraging clinical activity and institutional evidence in the most "cold" tumors, such as PDAC.
also provided preliminary data for triple combination therapy, suggesting that CXCR4/PD-1 blocking has the potential to improve the benefits of chemotherapy in Patients with PDAC.
Motixafortide is a short synthetic peptide that serves as a platform for cancer immunotherapy and has unique features that give it the potential to become a best-in-class CXCR4 antagonist.
CXCR4 is a chemofactor receptor and a proven therapeutic target that is overexpressed in many human cancers, including PDAC.
CXCR4 plays a key role in tumor growth, invasion, angiogenesis, metastasis and therapeutic resistance, and excessive expression of CXCR4 is associated with poor prognosis.
motixfortide mechanisms (Photo: BioLineRx) In many clinical and preclinical studies, motixafortide has been shown to influence "cold" tumors in a variety of modes of action, including immune cell migration, immune-effect T-cells immersion of tumors, reduction of immunosuppressive cells in the micro-environment of tumors (such as MDSCs), and the transformation of "cold" tumors into "hot" tumors, even if they are sensitive to the test.
currently, BioLineRx is working with Mercatoto to evaluate the combination drug regimen between Motixafortide and Keytruda.
, the company also partnered with Roche to combine motixafortide with Tecentriq.
Source: BioLineRx Announces Publication of Data from Ongoing COMBAT/KEYNOTE-202 Clinical Trial in Medicine.