Hollings enrolls first patient in new bifunctional antibody cancer trial

A patient at MUSC Hollings Cancer Center is the first to undergo treatment in a worldwide clinical trial focused on finding more effective treatment for people with HPV-negative head and neck squamous cell carcinoma that has returned or metastasized.

FORTIFI-NH01 is a randomized phase 2/3 trial of a first-in-class bifunctional antibody, ficerafusp alfa. This study is investigating if combining ficerafusp alfa with pembrolizumab, an immunotherapy that is already used in recurrent and metastatic head and neck squamous cell carcinoma (HNSCC), improves patient outcomes.

John Kaczmar, M.D., the trial’s site principal investigator at Hollings, is optimistic about the new combination. Hollings was a high enrolling center in the phase 1 study of ficerafusp alfa.

Although phase 1 studies focus on safety, Kaczmar was nonetheless able to see encouraging outcomes for many of his patients receiving the novel combination. Now, the new drug combination has moved on to a phase 2/3 study, with the hope of setting a new standard of care for patients with recurrent and metastatic HNSCC.

The first patient, Amy Suggs, decided to enroll in the trial after undergoing a grueling regimen of treatments over the past three years.

“I’ve already had multiple surgeries. I’ve had chemotherapy. I’ve had radiation. And this cancer still keeps coming back,” she said. “So we decided to try a different route.”

"Clinical trials like this give us the chance to potentially augment standard immunotherapy with novel immune approaches that might expand the universe of patients who are able to achieve the profound benefit that immunotherapy can provide."

John Kaczmar, M.D.

Clinical trials like this are critical for improving treatment options for challenging-to-treat cancers, like head and neck cancer, Kaczmar explained. For individual patients who need treatment now, they also offer the possibility of early access to the most promising therapies.

“For patients with recurrent or metastatic head neck cancer, pembrolizumab, or Keytruda, is the standard of care, either by itself or with chemotherapy. And for some people it is hugely beneficial – life-changing,” Kaczmar said.

“But for too many people, it isn't,” he continued. “Clinical trials like this give us the chance to potentially augment standard immunotherapy with novel immune approaches that might expand the universe of patients who are able to achieve the profound benefit that immunotherapy can provide.”

Suggs knows there’s a chance that she’s receiving pembrolizumab only instead of pembrolizumab with ficerafusp alfa. Comparing groups receiving and not receiving the study drug is how researchers determine whether the new combination is more effective than standard treatment. “To me, taking that chance is worth it if there’s even a small chance that I would actually get the (study) drug,” she said.

The study drug, ficerafusp alfa, is a bifunctional antibody. Typical antibodies recognize one foreign molecule. A bifunctional antibody has been created with two arms to engage two targets.

Ficerafusp alfa targets epidermal growth factor receptor (EGFR), a protein on the surface of many types of cancer, and human transforming growth factor beta, a signaling molecule that promotes tumor growth in the presence of EGFR.

The idea behind immunotherapy is to harness the body’s own immune system, and preclinical research indicated that ficerafusp alfa “remodels” the environment around the tumor, giving the body’s immune cells easier access to the tumor. And with two simultaneous targets, cancer cells are less likely to develop resistance. The combination is delivered via a weekly infusion.

Risk factors for head and neck squamous cell carcinoma include heavy alcohol or tobacco use and human papillomavirus (HPV) infection, although this cancer can affect anyone. Kaczmar noted that doctors have started to see an increase in unexplained HPV-negative HNSCC among younger women.

In addition, cancers caused by HPV tend to respond better to treatment, leading researchers to believe that different treatments are needed for HPV-positive and HPV-negative head and neck squamous cell carcinoma. This trial is testing a drug combination for people with the HPV-negative version.

Suggs knows firsthand how devastating this cancer is. The past three years have been painful and humbling. Throughout, she’s relied on her faith and the support of her employer, her husband, her parents and her brother. She hopes that her participation in this trial plays a part in improving care.

“I want to contribute in some way,” she said. “If they find something that will cure cancer, that would be awesome.”

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