Category Archives: Checkpoint Inhibitors

PD-L1 Expression correlates with outcomes in patients with melanoma

Keytruda (pembrolizumab) and Opdivo (nivolumab) are monoclonal antibodies that disrupt the PD-1 (Opdivo) / PD-L1 (Keytruda) pathway; they are approved by the FDA for the treatment of patients with unresectable melanoma, as well as other cancers including non-small cell lung cancer (NSCLC), head and neck cancer, renal cell carcinoma (Opdivo), and Hodg  kin lymphoma (Opdivo). Keytruda is limited to patients with NSCLC with a tumor proportion score (TPS) of greater than 50% for PD-L1 staining. Continue reading

BMS and PsoOxus collaborate on transgenic oncolytic virus plus nivolumab

BMS paid PsiOxus $50MM upfront for exclusive rights to develop PsiOxus’ NG-348 enadenotucirev, a systemically administered oncolytic adenovirus therapeutic, in combination with Bristol-Myers Squibb’s Immuno-Oncology checkpoint inhibitor Opdivo (nivolumab) to treat a range of solid tumor types in late-stage cancer patients. This is a “big deal” –  PsiOxus could receive up to $886 million in development, regulatory, and sales-based milestones, plus sales royalties. Continue reading

Opdivo combined with novel IL-2 prodrug immune stimulant

Bristol Myers Squibb (BMS) and Nektar Therapeutics announced a collaboration in which BMS’ PD-1 checkpoint inhibitor (Opdivo, nivolumab) will be combined with Nektar;s CD-122 agonist NKTR-214. Continue reading

How PD-1 abrogates the anti-tumor immune response

PD-1 inhibition (Figure 1) has quickly become a front-line therapy for non-small cell lung cancer and melanoma. Moreover, PD-1 and PD-L1 inhibitors are being tested in combination with other checkpoint inhibitors, targeted therapies, cancer vaccines, monoclonal antibodies, and other modalities. But, how does PD-1 blunt the anti-tumor immune response? Continue reading

Leap’s Two Early-Stage Immuno-Oncology Antibodies

Leap Therapeutics, an immuno-oncology company, recently reversed merge with Macrocure to become a publicly traded company, and received an investment of $10MM from current investors in order to advance two antibodies –  DKN-01, a humanized monoclonal antibody targeting the Dickkopf-1 (DKK1) protein on cancer cells, and TRX518, a humanized GITR agonist that augments T-cell responses against tumors. Continue reading

Blocking CD47 Innate Checkpoint Control for Cancer Treatment

Several companies, including Trillium, Celgene, Tioma, and Forty Seven are developing products that block CD47 for the treatment of cancer. Researchers have also shown that attacking CD47 may be a better approach to bone marrow conditioning prior bone marrow transplant. Continue reading

New data with temozolomide plus radiation for brain cancers

The results of two studies have demonstrated that the use of temozolomide (TMZ) plus radiation increases disease-free and overall survival in patients with glioblastoma and a low grade glioma called anaplastic glioma. Continue reading

Celgene Collaborates with Jounce Therapeutics on ICOS T-cell Stimulator

Checkpoint inhibitors, alone, are effective in 25% of patients when administered as a single agent. The goal of the collaboration between Celgene and Jounce is to address the other 75% of patients. The lead program is focused on ICOS, the Inducible T cell CO-Stimulator, a protein on the surface of T cells that can spur an immune response against a patient’s cancer. Continue reading

Mechanisms of Melanoma Resistance to PD-1 Checkpoint Inhibition

It is estimated that about 40 percent of patients with advanced melanoma, the deadliest form of skin cancer, will initially respond to an immunotherapy, but about a quarter of those 40 percent will relapse within three years of treatment. In order to identify the mechanisms by which resistance to PD-1 inhibition is mediated, UCLA researchers studied biopsies of melanoma tumors taken before and after treatment with Keytruda (pembrolizumab) in patients whose cancer had returned. Continue reading