ImmunoGen, Inc., a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, today announced initial safety and preliminary anti-tumor activity from the FORWARD II expansion cohort assessing mirvetuximab soravtansine in combination with Merck's anti-PD-1 therapy, KEYTRUDA® (pembrolizumab). The data are being presented at the European Society for Medical Oncology (ESMO) 2018 Congress, which is being held October 19-23, in Munich, Germany.
"A high unmet need exists in patients with platinum-resistant ovarian cancer, particularly for heavily pretreated patients, and the goal of this study is to assess whether the addition of a checkpoint inhibitor prolongs the clinical benefit of mirvetuximab soravtansine in later-line patients through concomitant activation of the immune system," said Ursula Matulonis, M.D., Chief, Division of Gynecologic Oncology, Dana-Farber Cancer Institute. "Preliminary activity seen with the mirvetuximab soravtansine and pembrolizumab combination is encouraging, especially when considering other combinations involving pembrolizumab used in this patient population, where recent clinical trials have reported overall response rates below 20 percent."
The data presented at ESMO were for 56 patients with platinum-resistant ovarian cancer, of whom 40 have medium or high folate receptor alpha (FRα) expression. Patients had received a median of 3 prior therapies (range 2-7).
The combination of mirvetuximab soravtansine (6 mg/kg adjusted ideal body weight) and pembrolizumab (200 mg, supplied by Merck) demonstrates favorable tolerability and encouraging activity. Adverse events were predominantly mild to moderate (≤ Grade 2), consistent with the known safety profiles of each agent.
Preliminary findings related to activity include:
- 83% of patients (45/54 with at least one post-baseline scan) experienced tumor shrinkage of target lesions in response to treatment with mirvetuximab soravtansine and pembrolizumab, with more robust reductions observed in patients with tumors expressing FRα at medium or high levels.
- Confirmed partial responses (PRs) were observed in 16 patients, with another 9 patients having unconfirmed PRs at the time of data analysis.
- In the subset of patients with medium or high FRα expression levels, the confirmed overall response rate (ORR) was 31 percent (95% CI, 17, 48), with a median progression-free survival (PFS) of 5.5 months (95% CI 2.8, 6.3) and a median duration (DOR) of 8.1 months (95% CI 4.2, upper bound not yet reached).
- At the time of analysis, the data were immature with 16 patients still on study (all with medium or high FRα expression) and a median follow-up of 8.3 months.
- For all patients evaluable for activity, the confirmed ORR was 30 percent (95% CI 18, 44), with a median PFS of 4.2 months (95% CI 2.8, 5.9). The median DOR data of 6.9 months (95% CI 4.2, 8.3) suggest a trend towards improvement over mirvetuximab soravtansine monotherapy.
"The combination of mirvetuximab soravtansine with pembrolizumab continues to demonstrate a favorable tolerability profile in women with platinum-resistant ovarian cancer, with preliminary activity consistent with mirvetuximab monotherapy in heavily pretreated patients," said Anna Berkenblit, M.D., Vice President and Chief Medical Officer of ImmunoGen. "The early duration of response data from the expansion cohort suggest a trend towards improvement over mirvetuximab monotherapy. As the data from this cohort continue to mature, we will use it to guide the further development of this novel combination, as part of our broader strategy to establish mirvetuximab soravtansine as the preferred combination therapy in ovarian cancer."