Ampligen Combo Safe, Effective in Treating Recurrent Ovarian Cancer, Phase 1 Study Shows

A combination of Hemispherx Biopharma‘s investigational treatment Ampligen (rintatolimod) with chemo-immunotherapy is safe and effective in treating women with recurrent ovarian cancer, according to the final report of a Phase 1 study.

While chemotherapy and immunotherapies have shown promise in fighting ovarian cancers, their activity may be boosted by increasing the number of immune cells infiltrating the tumors, researchers say.

Ampligen — approved in Argentina for severe cases of chronic fatigue syndrome — is an immune modulator that activates specific immune cells. It is expected to facilitate immune cell infiltration within the tumor.

Preclinical studies showed that Ampligen selectively reprogrammed the tumor’s microenvironment by promoting the accumulation of killer T-cells — immune cells that attack cancer cells — without attracting regulatory T-cells (Tregs). Tregs are potent immunosuppressive cells that contain immune responses, namely those against tumors.

These findings suggest that adding Ampligen to chemo-immunotherapy could give the immune system an additional advantage in the fight against ovarian cancer.

The Phase 1/2 study (NCT02432378), conducted at the University of Pittsburgh Medical Center, evaluated the safety and effectiveness of adding Ampligen and Intron A (interpheron alpha-2b) to Platinol (cisplatin) chemotherapy, the anti-inflammatory celecoxib, and an experimental dendritic cell-based vaccine (DC vaccine) in patients with recurrent ovarian cancer. The Ampligen is given by intraperitoneal administration — into the abdomen, where the tumor is located.

Interferon (IFN) alpha-2b, a molecule involved in the regulation of the immune system, is an approved immunotherapy for several types of cancer, and is thought to limit toxicity and boost the effectiveness of standard chemotherapies. It is being studied as an adjuvant therapy for ovarian cancer, meaning it’s applied after the initial treatment to lower the risk that the cancer will come back.

DC vaccines are personalized vaccines that rely on dendritic cells, immune cells that take up foreign material, including infectious agents or tumors, re-exposing pieces of it — called antigens — to immune cells, triggering immune responses against the foreign cells. Vaccination with dendritic cells that have taken up ovarian cancer antigens is a form of immunotherapy.

The study involved 40 women who had responded to platinum-based chemotherapy for six months or longer. Participants received Platinol and DC vaccine either alone or in combination with Ampligen and INF-alpha 2b.

The trial’s preliminary results showed that Ampligen had a similar effect to that observed in preclinical studies, inducing the infiltration of killer T-cells within the tumor without intensifying immunosuppressive responses.

Now, the final report of the recently completed Phase 1 portion of the study supported the safety of administering Ampligen intraperitoneally in combination with chemo-immunotherapy.

In the report, Brian Orr, one of the study’s lead investigators, said there was no evidence of additional toxicity when adding Ampligen to Platinol chemotherapy, since most of the severe adverse events reported with the combo therapy were commonly reported with Platinol single therapy.

“The Phase 1 study, in addition to generating excellent safety data, has also produced positive survival data with regard to the stage 4 ovarian cancer patients,” Robert Edwards, the trial’s principal investigator and chair of gynecologic services at Magee-Womens Hospital at the University of Pittsburgh School of Medicine, said in a press release.

These positive results are consistent with those obtained from clinical trials evaluating Ampligen in other types of cancer, said Thomas K. Equels, Hemispherx’s CEO.

“The results … support the impact Ampligen has in making the tumor more susceptible to host immunosurveillance and more susceptible to destruction by a host immune response in the presence or absence of additional immune or chemotherapeutic agents,” Equels said.

Based on the Phase 1 study results, a Phase 2 trial (NCT03734692) evaluating the safety and effectiveness of a combination therapy of Ampligen, Keytruda (pembrolizumab), and Platinol in women with recurrent ovarian cancer has already begun.

The trial, which is still recruiting participants at the University of Pittsburgh School of Medicine in Pennsylvania, is expected to enroll 45 ovarian cancer patients who responded to platinum-based chemotherapy for at least six months. Its primary goal is to determine the number of patients achieving at least a 30% reduction in tumor size.

Keytruda, marketed by Merck, is an immunotherapy used to treat various types of cancer. It works by preventing cancer cells from silencing immune cells produced to attack them, thus boosting anti-cancer responses.

Hemispherx expects that the Ampligen-Keytruda combo therapy will boost the anti-cancer response by promoting even further the recruitment to the tumor of immune cells ready to fight the cancer.