AACR Annual Meeting News: Merck, RGENIX, Verastem and More


While much of the world is focused on COVID-19, there is still a significant amount of research being conducted in various indications, including oncology. Some of the latest data is being unveiled at the American Association for Cancer Research (AACR) Annual Meeting, which is ongoing in a virtual setting this year due to the pandemic.

BioSpace has put together an overview of some of the presentations that have been made at this year’s conference.

Merck -- Merck presented interim data from Cohort B of KEYNOTE-555, a Phase I trial evaluating a 400 mg every six-week dosing regimen for its checkpoint inhibitor Keytruda in patients with metastatic melanoma. Study results demonstrated efficacy and safety comparable to findings from previous melanoma trials evaluating the anti-PD-1 drug as a monotherapy. Interim data showed an overall response rate (ORR) of 38.6% in patients who received Keytruda once every six weeks, the primary endpoint of the study. As previously announced, Merck resubmitted supplemental Biologics License Applications to the U.S. Food and Drug Administration to update the dosing frequency for Keytruda to include the six week option across all approved adult indications. The results of KEYNOTE-555 supported the resubmission, the company said.  

Rgenix – New York-based RGENIX, Inc. presented data on RGX-104, the company’s lead therapy in development. For the dose escalation stage of this Phase 1b study, RGX-104 was tested in combination with docetaxel across three different dose escalation cohorts. The results support further development of this regimen, the company said. RGX-104 is a small-molecule LXR agonist that modulates innate immunity via transcriptional activation of the ApoE gene. RGX-104 inhibits tumor angiogenesis and depletes myeloid derived suppressor cells (MDSC), thereby activating cytotoxic T-lymphocytes. MDSCs are associated with resistance to both checkpoint inhibitors (CPI) and chemotherapy, including docetaxel, providing a rationale for combination therapy with RGX-104. Consistent with this, RGX-104 plus docetaxel combination therapy is highly efficacious in pre-clinical models that demonstrate MDSC-associated docetaxel resistance, the company said. Clinical activity was associated with increases in T cell activation markers exceeding that generally observed with RGX-104 alone. As a result, the RGX-104/docetaxel regimen is being evaluated in a phase Ib/II expansion study that has begun enrolling patients with relapsed/refractory extensive stage small-cell lung cancer (ES-SCLC) or high grade-neuroendocrine tumors (HG-NET).

Alligator Bioscience – Sweden’s Alligator Biosciences presented the status of the ongoing Phase I clinical trial with the bispecific drug candidate ATOR-1015 developed as tumor-directed therapy for metastatic cancer. So far, doses of 400 mg have been evaluated in the ongoing study and the current dosing is 600 mg. As of the presentation,18 patients with varying cancer forms, including colon cancer, eye melanoma, pancreatic cancer, ovarian cancer, gallbladder cancer, gastric cancer and skin cancer, have been treated and evaluated in terms of safety. ATOR-1015 has so far been well tolerated. The adverse events in the study were generally mild and no serious immune-related or dose-limiting adverse events have been reported, the company said.

Verastem – Results from the ongoing Phase I study investigating VS-6766, Verastem’s RAF/MEK inhibitor, in combination with defactinib, its FAK inhibitor, in patients with KRAS mutant advanced solid tumors were presented at AACR. In the low-grade serous ovarian cancer (LGSOC cohort), among the patients with KRAS mutant tumors, four patients responded, for an overall response rate (ORR) of 67%. Median time on treatment was 20.5 months. In the KRAS mutant NSCLC cohort, one patient achieved a partial response and 8 patients achieved disease control. In this cohort, 70% of patients continued on treatment at least 12 weeks and 30% of patients continued on treatment at least 24 weeks. Based on an observation of higher response rates seen in patients with KRASG12V mutations in the investigator-initiated Phase I combination study, Verastem conducted a combined analysis with data from the combination study and the prior single-agent study that used a twice-weekly dosing schedule of VS-6766 to get a more complete picture of activity in KRASG12V mutations. The subsequent, combined analysis showed a 57% ORR; as a single agent and in combination with defactinib in KRASG12V mutant NSCLC. Similarly, the combined analysis showed a 60% ORR as a single agent and in combination with defactinib (2/3 patients) in KRASG12V mutant gynecologic cancers, the company said.

AIVITA Biomedical – California-based AIVITA presented data from its Phase II study of AV-GBM-1 in newly diagnosed glioblastoma, included data obtained through March 2020. The study has completed enrollment, and the treatment has been well-tolerated to date with encouraging preliminary survival data, the company said. Data from a Phase II clinical trial of AVOVA-1 in advanced ovarian cancer, showed the trial is progressing as planned and the treatment has been well-tolerated. Enrollment for the study continues for both tumor collection and randomization.

Ribon Therapeutics – Cambridge, Mass.-based Ribon presented preclinical data from a study of RBN-2397, a first-in-class PARP7 inhibitor. The preclinical data showed the PARP inhibitor achieved complete tumor regressions in preclinical cancer models. RBN-2397 is Ribon’s lead program and is currently being evaluated in a Phase I clinical trial in advanced-stage solid tumors. In vitro data illustrated the immune-suppressive role PARP14 plays in the tumor microenvironment, suggesting PARP14 targeting could generate an anti-cancer inflammatory response similar to that seen using checkpoint inhibition, the company said.

GRAIL At AACR, GRAIL presented data from its investigational multi-cancer early detection blood test. The Bay Area company said its multi-cancer early detection technology can detect more than 50 cancers, with a very low false positive rate of less than one percent, through a single blood draw. When a cancer signal is detected, the test can also identify where the cancer is located in the body, GRAIL added. This technology could be particularly useful in directing a more efficient diagnostic workup in symptomatic patients who are being evaluated for cancer. GRAIL said the data represents. a pre-specified sub-group from the company’s foundational Circulating Cell-free Genome Atlas study. In the sub-group analysis reported at AACR, participants being evaluated for suspicion of cancer were classified as clinically confirmed cancer or clinically confirmed non-cancer. In the confirmed non-cancer group, all training and validation samples were correctly predicted as non-cancer, or 100% specificity.

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