There are mainly five types of cancer that affects a woman’s reproductive organs including cervical, ovarian, uterine, vaginal, and vulvar. A sixth type of gynecological cancer that is very rare is the fallopian tube cancer.
Major Pharma giants such as, Clovis Oncology and Seagen are looking at this opportunity to present their data readouts for different promising assets in Ovarian Cancer.
Efficacy and safety of Rucaparib maintenance treatment in patients with platinum-sensitive, recurrent ovarian carcinoma
In September 2017, Clovis Oncology published the positive results from the confirmatory Phase III (ARIEL3) trial of rucaparib. Based on the data from this result, in April 2018, rucaparib got its approval by the FDA for the maintenance treatment of recurrent epithelial ovarian cancer having homologous recombination deficiency (HRD) positive status. The drug was being tested as a switch maintenance therapy after platinum-based chemotherapy in platinum-sensitive patients, which achieved primary endpoint of progression-free survival (PFS). The median progression-free survival in patients with a BRCA-mutant carcinoma was 16.6 months in the rucaparib group versus 5.4 months in the placebo group.
The company is going to publish the results from Phase III (ARIEL3) trial as maintenance treatment in patients with platinum-sensitive, recurrent ovarian carcinoma who are not associated with homologous recombination deficiency (HRD). Till date, there are only 3 FDA approved PARP inhibitors which are used as a switch maintenance therapy (i.e., olaparib, niraparib, and rucaparib). These 3 PARP inhibitors are approved as switch maintenance therapy in HRD+ patients whereas HRD- patients face significant unmet need as they have to go for switch maintenance with bevacizumab, but switch maintenance with a PARP inhibitor has a greater impact compared with bevacizumab in platinum-sensitive recurrent ovarian cancer.
ATHENA–MONO: A Phase III trial evaluating rucaparib monotherapy as maintenance treatment following response to first-line platinum-based chemotherapy in ovarian cancer
In March 2022, Clovis oncology published results from Phase III ATHENA-MONO trial in patients suffering with advanced ovarian cancer as a first-line maintenance monotherapy compared with placebo after treatment with platinum-based chemotherapy regardless of the biomarker status. The median PFS (mPFS) was 20.2 months in the rucaparib arm and 9.2 months in the placebo arm. The patients in the HRD+ subgroup had mPFS of 28.7 months versus 11.3 months in the placebo group.
Clovis oncology also revealed that the data from this trial will support for supplemental new drug application (sNDA) filing, the label expansion for which will be submitted to the FDA in Q2 2022. Company also recently announced the late breaking abstract (LBA) of the ATHENA-MONO trial to be presented at the ASCO 2022 conference where the company will be presenting the additional Phase III data from this trial which will complement the previously announced topline data.
Abstract Number - 5507
Seagen to present Tisotumab vedotin (TV) + Pembrolizumab interim results from ENGOT Cx8/GOG 3024/innovaTV 205 trial in patients with first-line recurrent or metastatic cervical cancer
Seagen is all set to present interim results from the dose-expansion cohorts of the innovaTV 205 trial of Tivdak (tisotumab vedotin-tftv) in combination with other anticancer agents in patients with recurrent metastatic cervical cancer
Tisotumab vedotin is being co-developed by Genmab and Seagen. It has already been approved for adult patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy (2L/3L). Now the company has shifted its focus towards the first-/second-line treatment of patients with recurrent or metastatic cervical cancer and is planning to present interim results from the dose-expansion cohorts of the innovaTV 205 trial.
TV monotherapy has received the US accelerated approval for previously treated r/mCC with based on clinically meaningful tumor response rate and duration of response (DoR) reported from the GOG-3023/ENGOT-cx6/innovaTV 204 study. innovaTV 205, a Phase I/II trial is evaluating tisotumab vedotin, as monotherapy and in combination with certain other anti-cancer agents for first- and second-line treatment of patients with recurrent or advanced cervical cancer. In September 2021, interim results were presented at the European Society for Medical Oncology Annual Congress from two cohorts of the Phase Ib/II innovaTV 205 trial. Both combinations showed encouraging, durable anti-tumor activity and demonstrated a manageable and acceptable safety profile. The company is planning to present interim results from a third dose-expansion cohort evaluating 1L TV + pembro in patients with r/mCC.
Ovarian cancer is associated with the highest mortality and most diseases are diagnosed at an advanced stage, which impaires the chances of prolonged complete remission. The current SoC in the first-line management of advanced stage includes surgery in an expert center with platinum-based chemotherapy. Previously anti-angiogenic agents were used in the maintenance setting has improved PFS rate over chemo alone and these days PARP inhibitors are increasingly used which have demonstrated substantial efficacy, mainly in patients with germinal or somatic BRCA mutations. But, the current approvals of PARP inhibitors in patients with recurrent diseases exclude those who previously treated with PARPi, whether they have progressed during maintenance on PARPi or if they relapsed after the end of the maintenance. It is unclear whether the mechanisms of biological resistance are similar in the two cases and therefore whether there is an interest in re-challenging these patients pre-treated with PARPi.
Clovis oncology is mostly involved in the label expansion of Rucaparib for newer patient segments. For first-line maintenance therapy of ovarian cancer Rucaparib is going to give tough competition to Niraparib as it has the median PFS of 21.9 months in HRD+ patients while Rucaparib has already shown mPFS of 28.7 months which can have a significant edge over the already approved therapies. Also, the company is trying this drug in recurrent patients not associated with HRD status where exists an unmet need. Therefore, Rucaparib might get the benefits of first-mover advantage in this patient population.
Also, the initial interim results of tisotumab vedotin had encouraging response rates in combination with carboplatin and also in combination with pembrolizumab (as per interim data published), it can be weighed down by a major side effect. Since Tivdak has been associated with ocular toxicity. However, considering Tivdak is the first and only FDA-approved ADC for patients with recurrent or metastatic cervical cancer with disease progression on or after chemotherapy we look forward to the encouraging data from the combination.