Discussion of Phase-II Proof Of Concept Study
Study QPT-ORE-002 (NCT01616303) was a phase 2, randomized, multi-center study, assessing first-line chemotherapy (carboplatin-paclitaxel) versus combination chemoimmunotherapy (oregovomab + carboplatin-paclitaxel) in 97 patients with advanced epithelial ovarian, adnexal or peritoneal carcinoma following optimal debulking surgery.
In the above study, Subjects treated with oregovomab + paclitaxel/carboplatin had a clinically significant improved PFS (median 41.8 months) compared to paclitaxel/carboplatin alone (median 12.2 months) by the K-M method (p=0.0027) and a HR=0.44 by multivariate Cox PH method (p=0.0029).
The subjects treated with oregovomab + paclitaxel/carboplatin also had a clinically significant improved OS (median NE) compared to paclitaxel/carboplatin alone (median 43.2 months) by the K-M method (p=0.0042) and a HR=0.34 by the multivariate Cox PH method (p=0.0077), as well as a clinically significant improved time to clinical progression (TTCP) (median 43.1 months) compared to paclitaxel/carboplatin (median 13.6 months) by the K-M method (p=0.0014) and a HR=0.40 by the multivariate Cox PH method (p=0.0019).
Subjects treated with oregovomab + paclitaxel/carboplatin had minimal and low grade additonal adverse event issues as compared to paclitaxel/carboplatin chemotherapy.
Sensitivity analyses using worst-case scenarios and follow-up quality supported the clinical outcome results and demonstrated a lack of systemic bias.
A potential for clinical benefit from the addition of oregovomab treatment to standard-of-care paclitaxel/carboplatin chemotherapy in front-line treatment of patients with Stage III/IV cancer of epithelial ovarian, tubal, or peritoneal origin after optimal debulking surgery, is supported by the magnitude of improvement evidenced by the clinical outcome endpoints in this multicenter study. Oregovomab has a novel immunotherapeutic mechanism of action that in combination with the immunomodulating effects of the standard-of-care chemotherapy has generated evidence that it has the potential to trigger immune response which may substantially improve standard-of-care chemotherapy, with an improved safety profile. It represents a potential advancement in the front-line management of ovarian cancer.
Publications of Results:
Brewer M, Angioli R, Scambia G, Lorusso D, Terranova C, Panici PB, Raspagliesi F, Scollo P, Plotti F, Ferrandina G, Salutari V, Ricci C, Braly P, Holloway R, Method M, Madiyalakan M, Bayever E, Nicodemus C. Front-line chemo-immunotherapy with carboplatin-paclitaxel using oregovomab indirect immunization in advanced ovarian cancer: A randomized phase II study. Gynecol Oncol. 2020 Mar;156(3):523-529. doi: 10.1016/j.ygyno.2019.12.024. Epub 2020 Jan 6.
Battaglia A, Buzzonetti A, Fossati M, Scambia G, Fattorossi A, Madiyalakan MR, Mahnke YD, Nicodemus C. Translational immune correlates of indirect antibody immunization in a randomized phase II study using scheduled combination therapy with carboplatin/paclitaxel plus oregovomab in ovarian cancer patients. Cancer Immunol Immunother. 2020 Mar;69(3):383-397. doi: 10.1007/s00262-019-02456-z. Epub 2020 Jan 3. Erratum in: Cancer Immunol Immunother. 2020 Jul;69(7):1389.