Varlilumab-Opdivo Combo Stabilizes or Shrinks Tumors in 80% of Solid-cancer Patients, Trial Shows

Varlilumab-Opdivo Combo Stabilizes or Shrinks Tumors in 80% of Solid-cancer Patients, Trial Shows

A combination of varlilumab and Opdivo (nivolumab) stopped tumor growth in 80 percent of the 36 patients in a Phase 1 clinical trial, according to varlilumab’s developer, Celldex Therapeutics.

Tumors shrank significantly in three of the patients, Celldex noted.

The findings applied to patients with solid tumors that had spread to other parts of their body, who had been heavily treated with other therapies, and whose tumors had little or no PD-L1 protein. PD-L1 is believed to play a role in suppressing the immune system.

Varilumab activates immune cells known as T-cells to fight cancer, which is why scientists call it a T-cell activating agent. Opdivo, a therapy known as an immune checkpoint inhibitor, blocks a signal that prevents activated T-cells from attacking cancer.

Those who took part in the study were expected to show a minimal response to an immune checkpoint inhibitor, so the discovery that the combo treatment stabilized or reduced 80 percent of the patients’ cancers was satisfying.

Celldex presented the trial results at the American Society of Clinical Oncology annual meeting in Chicago, June 2-6. The presentation was titled “Clinical Results with Combination of Anti-CD27 Agonist Antibody, Varlilumab, with Anti-PD1 Antibody Nivolumab in Advanced Cancer Patients,

“Combining PD-1 inhibition with a potent T-cell activating agent provides the opportunity to broaden the number of patients that benefit from checkpoint blockade,” Dr. Rachel E. Sanborn, an oncologist at the Providence Cancer Center in Portland, Oregon, said in a press release.

“While early, we have evidence that this combination does not add toxicity, can turn some ‘immune-cold’ tumors hot, and may have clinical [treatment] benefit, including in some patients who are not likely to respond to monotherapy [only one drug],” Sanborn added.

Varlilumab targets the CD27 protein on the surface of immune T-cells. By binding to CD27, it activates T-cells, strengthening their response against cancer cells.

The Phase 1/2 trial (NCT02335918) is evaluating the combination of varlilumab and Opdivo’s effectiveness and safety against several solid cancers.

The Phase 1 dose-escalating part of the study included 36 patients. Twenty-one had colorectal cancer, eight ovarian cancer, four melanoma, and three squamous cell carcinoma of the head and neck.

Researchers tested three doses of varlilumab while keeping the Opdivo dose the same.

Eighty percent of the patients’ tumors stabilized or shrank. with three patients achieved the partial responses.

A patient with PD-L1-negative colon cancer achieved a 95 percent decrease in tumor size, with the combo eliminating four of the five lesions the patient had before treatment.

A patient with squamous cell head and neck cancer who had low levels of PD-L1 in his tumor saw the tumor shrink by 59 percent after treatment. In addition, his disease did not progress for 6.7 months.

The tumor of a patient who had PD-L1-negative ovarian cancer shrank by 49 percent. She ended up having to discontinue treatment due to a toxic reaction to Opdivo, however.

Overall, the combo therapy was well tolerated, with no significant toxicity associated with varlilumab.

The results indicated that the dual therapy can significantly benefit patients without being toxic, researchers said.

“Further elucidating the role of intermittent versus chronic T-cell activation through the comparison of alternate varlilumab dosing regimens is an essential component of the ongoing Phase 2 study and could be important in optimizing the potential of this combination,” Sanborn said.

Researchers are expected to complete patient enrollment in the Phase 2 portion of the trial in the first quarter of 2018. It will also include patients with renal cell carcinoma and glioblastoma.

Its primary measure of effectiveness in all cancers except glioblastoma will be the percentage of patients who respond to the combo. The yardstick for glioblastoma will be patients’ 12-month overall survival rate.

Celldex and Bristol-Myers Squibb expect to present the Phase 2 study data at a future medical meeting.