Ongoing research on cancer vaccine candidate BNT111 at the Atlantic Health System


Over the past decades, research into immunotherapeutic agents for cancer has resulted in more and more treatment regimens for patients with solid tumors as well as hematological malignancies who receive treatment in advanced or metastatic settings. .

At the forefront of this cutting-edge research are clinical trials evaluating different immunotherapy strategies in melanoma, which has been a stronghold for cancer research into the immune mechanisms of the antitumor response.

“I have specialized in melanoma for several years now, since the beginning of my career. Of all the cancers we treated, melanoma seemed to have the strongest connection to our immune system,” said Eric D. Whitman, MD, medical director of Atlantic Health System’s Oncology Service Line in Morristown, New Jersey, in an interview. with CancerNetwork®. “Melanoma was the first cancer to show a response to immune therapy, and that really intrigued me as a clinician.”

Whitman said his interest in research was a big part of why he wanted to specialize in the treatment of melanoma. He was one of the first researchers in the first wave of immunotherapies and continues to investigate new agents in different treatment settings. In this era of modern research, one strategy in space is to fight disease in patients who initially show resistance to traditional immune checkpoint inhibitors.

“There are now several FDA-approved drugs that use the immune system to fight cancer, but they are not always effective. In the case of melanoma, about half of patients – for reasons we really don’t understand – will still need treatment for their metastatic cancer, after traditional treatment has failed.

At Atlantic Health System, innovative cancer therapies are available through a strong offering of open-label clinical trials that are recruiting participants in all disease settings. One such trial for which Whitman is the site principal investigator for BioNTech SE’s Phase 2 BNT111-01 (NCT04526899) ​​trial of the use of a proprietary cancer vaccine with or without an endpoint inhibitor. anti-PD-1 control.

BNT111 emerges for advanced melanoma

Therapeutic cancer vaccines can work by training the patient’s immune system to recognize malignant cells and can be coupled with traditional immunotherapy to enhance the native anti-tumor response. And because approved treatments for patients with advanced melanoma who don’t respond to traditional immunotherapies are lacking, the combination of the 2 modalities has garnered interest and shown promise in early trials.

One such agent is BioNTech’s FixVac program candidate BNT111, which is an intravenous immunotherapy encoding 4 cancer-specific antigens delivered as an RNA-lipoplex formulation.

“Each of these drugs tries to teach the immune system a common protein [in melanoma] this should be recognized. Each component is similar in concept to a messenger RNA vaccine, so it’s a fragment of the RNA that makes up a melanoma-associated antigen or protein that our immune system should recognize,” Whitman said. “You give all four together, to increase the chance that at least 1 or 2 of them will help fight that person’s melanoma.”

The Lipo-MERIT Phase 1 clinical trial (NCT02410733) evaluating BNT111 in melanoma patients following exposure to an immune checkpoint inhibitor indicated that the agent has the potential to induce responses, either either as a single agent or in combination with immunotherapy, while strongly increasing immunity against vaccine antigens.1

“The main takeaways from the Phase 1 study are that it’s safe and we now know the dose,” Whitman said. “The second thing is that there have been responses. It’s preliminary, but looking at these results, it gives you hope that this new drug will benefit patients, either on its own or in combination with more standard immunotherapy.

In November 2021, BNT111 was granted accelerated designation for the potential treatment of advanced melanoma, which is granted to promising agents in serious conditions for which there is an unmet need.2

“I believe this designation will help to obtain [BNT111] to patients more quickly. Half of our patients with advanced melanoma fail standard treatment and no longer have an FDA-approved treatment option. By granting this expedited designation, [the FDA] says this drug has a great chance of helping these patients and addressing this unmet need,” Whitman said.

Research in progress with BNT111

Currently, BNT111 is in a phase 2 trial – with arms for single-agent treatment, in combination with cemiplimab (Libtayo) or cemiplimab alone – as a treatment for patients with refractory Stage III/ in relapse to anti-PD-1 or IV melanoma. Recruitment is estimated at 180 patients and the primary endpoint is the objective response rate (ORR) in patients treated with BNT111 plus cemiplimab. Secondary endpoints include ORR in either monotherapy arm, duration of response, disease control rate, and progression-free survival.

Patients are eligible for the trial if they are over the age of 18 and have histologically confirmed unresectable Stage III or IV metastatic cutaneous melanoma that is measurable by RECIST 1.1 criteria. They must have had prior exposure to an approved regimen containing anti-PD-1 treatment for 12 consecutive weeks, radiological progression confirmed by 2 scans, and confirmed disease progression within 6 months of this treatment, regardless of the intermediate processing.

“The ideal candidate for this trial is someone with advanced melanoma who has not responded to standard therapy,” Whitman said. “They no longer have FDA-approved options. One of the important things for this trial is that they couldn’t have had such serious adverse effects with FDA-approved immunotherapies.

Another big feature of the trial that Whitman highlighted was the ability for patients who are randomized to a single-agent arm to cross over to receive the combination therapy. “[Patients] always worry about being randomized. The interesting part of this trial is that if they are randomized to BNC111 alone or cemiplimab alone, and the cancer grows through that, then you can be crossed over to get the combination.

The references

  1. Sahin U, Oehm P, Derhovanessian E, et al. An RNA vaccine boosts immunity in melanoma treated with a checkpoint inhibitor. Nature. 2020;585(7823):107-112. doi:10.1038/s41586-020-2537-9
  2. BioNTech Receives Fast-Track Designation from the FDA for its FixVac BNT111 Candidate in Advanced Melanoma. Press release. BioNTech. November 19, 2021. Accessed February 11, 2022.


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