FORWARD II Triplet Combination Demonstrates Encouraging Anti-tumor Activity

General images of ESMO 2019 Congress being held in Barcelona, Spain, September 27 - October 1, 2019. Courtesy European Society for Medical Oncology (ESMO). Used with Permission.
General images of ESMO 2019 Congress being held in Barcelona, Spain, September 27 - October 1, 2019. Courtesy European Society for Medical Oncology (ESMO). Used with Permission.

Safety and overall response data from the Phase Ib FORWARD II triplet cohort evaluating mirvetuximab soravtansine in combination with carboplatin and bevacizumab (Avastin®; Genentech/Roche) in patients with recurrent, platinum-sensitive ovarian cancer were presented at the European Society for Medical Oncology (ESMO) 2019 Congress being held September 27 – October 1, 2019 in Barcelona, Spain.

Mirvetuximab soravtansine, also known as IMGN853, is the first folate receptor alpha (FRα)-targeting antibody-drug conjugate or ADC. It uses a humanized FRα-binding antibody to target the ADC specifically to FRα-expressing cancer cells and a potent anti-tumor agent, the maytansinoid DM4, chemical derivative of maytansine, to kill the targeted cancer cells.

Anticancer properties of maytansinoids have been attributed to their ability to disrupt microtubule function.

MabPlex
ADC Bio
Lonza
 

Mirvetuximab soravtansine has shown single agent clinical activity and favorable safety in a phase I trial.

Based on the preliminary data, the FORWARD II triplet combination demonstrates encouraging anti-tumor activity and which support an ongoing study in platinum-sensitive patients.

David O’Malley, MD, Professor, Director of Gynecologic Oncology and Co-Director, Gynecologic Oncology Phase I Program at The Ohio State University and the James Cancer Center, and FORWARD II Principal Investigator.

Trial design
The FORWARD II study is an open-label, non-randomized phase Ib/II clinical trial which studies mirvetuximab soravtansine in combination with bevacizumab, carboplatin, or pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer that express medium or high levels of FRα as well as a triplet combination of mirvetuximab soravtansine plus carboplatin and bevacizumab in patients with platinum-sensitive ovarian cancer that express medium or high levels of FRα.

“The initial results from the triplet combining mirvetuximab soravtansine with both bevacizumab and carboplatin build nicely off of the encouraging data previously generated when mirvetuximab was paired individually with each of these agents,” noted David O’Malley, MD, Professor, Director of Gynecologic Oncology and Co-Director, Gynecologic Oncology Phase I Program at The Ohio State University and the James Cancer Center, and FORWARD II Principal Investigator.

“The anti-tumor responses observed with this combination compare favorably to those of other triplets and I look forward to reporting longer-term efficacy data, as we seek to provide new treatment options for patients with recurrent, FRα-positive platinum-sensitive ovarian cancer.”

Key Findings

  • In 41 patients with recurrent platinum-sensitive disease with medium or high folate receptor alpha (FRα) expression levels who have received up to two prior lines of therapy, the confirmed overall response rate (ORR) for the triplet was 83%, with a complete response (CR) rate of 17%.
  • In a subset of 31 patients with only 1 prior line, the confirmed ORR was 90%, with a CR rate of 19%.
  • These efficacy outcomes are encouraging relative to those reported in similar patient populations for other carboplatin and bevacizumab-based triplets.
  • With a median follow up of 9.3 months, progression-free survival (PFS) data are maturing.
  • The combination of full dose mirvetuximab soravtansine, carboplatin and bevacizumab is well tolerated.
  • No new safety signals were seen; adverse events observed with the triplet were as expected based on the side effect profiles of each agent, with thrombocytopenia as the most common cause of drug-related discontinuations.
  • Post-carboplatin (median 6 cycles), mirvetuximab soravtansine and bevacizumab continuation/maintenance is well tolerated.

“We are encouraged by the initial safety and overall response data from our triplet cohort, demonstrating that full-dose mirvetuximab soravtansine can be combined safely with the standard dosing for both bevacizumab and carboplatin,” said Anna Berkenblit, M.D., Vice President and Chief Medical Officer of ImmunoGen.

“We are continuing to follow patients for progression-free survival and look forward to initiating the next set of studies to support a path to registration in platinum-sensitive ovarian cancer,” Berkenblit concluded.

Clinical trials
First-in-Human Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Mirvetuximab Soravtansine in Adults With Ovarian Cancer and Other FOLR1-Positive Solid Tumors (IMGN-0401) – NCT01609556
Study of Mirvetuximab Soravtansine in Comb. With Bevacizumab, Carboplatin, PLD, Pembrolizumab, or Bevacizumab + Carboplatin in Adults With FRa + Adv. EOC, Primary Peritoneal or Fallopian Tube Cancer – NCT02606305

Reference
[1] David M. O’Malley M.D., James Comprehensive Cancer Center, The Ohio State University, Columbus, OH. Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with carboplatin and bevacizumab: Initial results from a Phase 1b study in patients with ovarian cancer. Abstract #1028P. Date: Sunday, September 29, 2019 | Time: 12:00 p.m. CEST/6:00 a.m. ET