Vaccines lead charge in cervical cancer


Inovio Pharmaceuticals’ collaboration with AstraZeneca on INO-3112, announced today, demonstrates that cervical cancer is one space where vaccines are on equal footing with other types of immunotherapies.

A therapeutic human papillomavirus (HPV) vaccine, INO-3112 is in early phase II studies, and Inovio is preparing to put one component of that vaccine, VGX-3100, into phase III next year. Given that chemoradiation therapy is the typical treatment for advanced HPV, targeted options would be welcome (see table below).


Astra paid $27.5m up front to Pennsylvania-based Inovio for access to INO-3112 plus two additional DNA-based cancer vaccines. The UK group said it plans to test the Inovio candidate in combination with its own immunotherapy agents; it did not specify which ones, although its anti-PD-L1 antibody durvalumab (MEDI4736) is the only immunotherapy it has in advanced development in cervical cancer.

INO-3112 is currently in an open-label phase I/IIa trial in patients with inoperable HPV 16 or 18 cervical cancer. This trial combines chemoradiation with the vaccine administered intramuscularly, followed by electroporation; results should be available next year. The European Organisation for Research and Treatment of Cancer is also initating a trial testing it as an adjuvant as well as combination therapy with chemoradiation.

The vaccine is composed of VGX-3100, a DNA vaccine from predecessor company VGX Pharmaceuticals, and a DNA-based IL-12 immune activator.

VGX-3100 is more or less the most advanced candidate in this space in the west, and Inovio is preparing to put the agent into a phase III trial in cervical dysplasia in early 2016. As it will treat only the precancerous cell abnormality, it does not for now conflict with the combined agent that Astra just licensed – Inovio no doubt will want to keep it that way to maximise its commercial potential.

HPV vaccine candidates for cancer treatment
Product Company Trial ID
Phase III
HPV-positive gynaecological tumours Cervical Cancer Vaccine Xiamen Innovax Biotech NCT01735006
Phase II 
Cervical cancer ADXS-HPV Advaxis/Biocon NCT01266460
INO-3112 Inovio Pharmaceuticals
ISA101 ISA Pharmaceuticals NCT02128126
Cervical dysplasia VGX-3100 Inovio Pharmaceuticals NCT01304524
BLS_ILS_E710c BioLeaders NCT01826045

To fund itself through to the end of 2018, including financing the VGX-3100 trial, Inovio sold $87.4m-worth of shares in May; the group now has $155m in cash and short-term investments. The Astra fee and any milestones emerging from that collaboration will help Inovio meet that funding guidance.

Not alone

A review of the phase II HPV vaccine pipeline in cervical cancer shows that with two candidates Inovio is in a leading position. However, it does not have the space all to itself.

For example, Xiamen Innovax Biotech is well into a 6,000-patient phase III trial in an array of gynaecological cancers, a 6,000-patient study scheduled to conclude in 2018. Advaxis, as with Inovio, has benefited from support from an academic collaboration, with the Gynecologic Oncology Group having put it into a phase II trial; Astra has also tested the vaccine with durvalumab in phase I/II.

Private Netherlands-based group ISA Pharma looks to be nearing the end of its trial in collaboration with the Dutch Cancer Society. As with many of these vaccines, it is being tested in HPV-positive tumours in other locations than the cervix; Bristol-Myers Squibb has one such trial ongoing in combination with Opdivo.

Cancer vaccines have had a rough ride, but with immunotherapies all the rage in oncology they are getting a second look as an assist to such approaches as checkpoint inhibitors. In diseases with an HPV origin there appears to be a firmer rationale for their use, so it is not surprising to see companies like Inovio and Advaxis getting a long look.

To contact the writer of this story email Jonathan Gardner in London at or  follow @ByJonGardner on Twitter

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