FOLR1 positive Ovarian Cancer

PICCOLO trial met its primary endpoint of objective response rate (ORR) Data from the study will be presented at a future medical meeting NORTH CHICAGO, Ill., June 6, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) announced today positive topline results from the Phase 2 PICCOLO trial evaluating investigational mirvetuximab soravtansine (ELAHERE®) monotherapy in heavily pre-treated patients with folate receptor-alpha (FRα) positive, platinum-sensitive ovarian cancer (PSOC). The study met its primary endpoint with an objective response rate (ORR) of 51.9% (95%CI 40.4 – 63.3%). In addition, the median duration of response (DOR), a key secondary endpoint, was 8.25 months. The safety profile of mirvetuximab soravtansine was consistent with findings from previous studies, and no new safety concerns were identified. Full data from the PICCOLO study will be presented at a future medical meeting. "Significant unmet needs remain for patients with platinum sensitive disease, as each subsequent line of therapy in this setting is associated with decreased efficacy and tolerability, which reinforces the need for treatment alternatives for these patients," said Angeles Alvarez Secord, M.D., M.H.Sc., from the Duke Cancer Institute. "The PICCOLO data further support the potential of mirvetuximab soravtansine for platinum-sensitive ovarian cancer patients." About PICCOLO PICCOLO is a single arm Phase 2 trial evaluating the efficacy and safety of mirvetuximab soravtansine monotherapy in patients with FR-alpha high platinum-sensitive ovarian cancer who have received at least two prior lines of platinum containing therapy or have a documented platinum allergy. The primary end point is objective response rate (ORR), and the key secondary endpoint is duration of response (DOR). The PICCOLO study was designed to statistically rule out an objective response rate of 28% or lower, as excluded by the lower bound of the confidence interval, a response rate which has been observed with non-platinum, single-agent chemotherapy in platinum-sensitive disease. Patients with PSOC with multiple prior lines of platinum-based therapy or who are ineligible for platinum-based therapy, as in the population in PICCOLO, have no established benchmark standard of care, particularly after disease progression on a PARP inhibitor. Mirvetuximab soravtansine is also being studied in PSOC in the Phase 3 GLORIOSA trial, in combination with bevacizumab versus bevacizumab alone in maintenance after second-line platinum-doublet therapy. About Ovarian Cancer Ovarian cancer is the leading cause of death from gynecological cancers in the United States. Each year, approximately 20,000 patients are diagnosed. Most patients present with late-stage disease and will typically undergo surgery followed by platinum-based chemotherapy. Unfortunately, the majority of patients will experience recurrence of their disease and require multiple subsequent lines of therapy, with decreasing efficacy and tolerability. Patients who initially respond to platinum-based chemotherapy and relapse 6 months or longer after the initial treatment were classified as platinum sensitive, while patients who relapse within under 6 months after platinum-based chemotherapy were considered platinum resistant. Platinum-based chemotherapy remains the most active treatment for earlier lines of ovarian cancer. The benefit of retreatment with platinum is generally less with each subsequent line of therapy. While platinum-based doublets predominate treatment for front- and second-line patients based on results from randomized trials, there is no generally accepted standard of care with a clear efficacy benchmark based on prospective trials in third-line or later patients, particularly those whose cancers have progressed on PARP inhibitors. About Mirvetuximab Soravtansine Mirvetuximab soravtansine is a first-in-class ADC comprising a folate receptor alpha-binding antibody, cleavable linker, and the maytansinoid payload DM4, a potent tubulin inhibitor designed to kill the targeted cancer cells. Mirvetuximab soravtansine approved under the brand name ELAHERE® in the United States has received regulatory approval in adults with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens. Select patients for therapy based on an FDA-approved test. The Marketing Authorization Application (MAA) for ELAHERE in Europe has been accepted by the European Medicines Agency (EMA). Regulatory submissions for ELAHERE are also under review in multiple other countries. The safety and efficacy of mirvetuximab soravtansine has not been established for platinum-sensitive ovarian cancer. ELAHERE® (mirvetuximab soravtansine-gynx) U.S. USE and IMPORTANT SAFETY INFORMATION What is ELAHERE? ELAHERE is a prescription medicine used to treat adults with folate receptor-alpha positive ovarian cancer, fallopian tube cancer, or primary peritoneal cancer who: • have not responded to or are no longer responding to treatment with platinum-based chemotherapy and • have received 1 to 3 prior types of chemotherapy. Your healthcare provider will perform a test to make sure that ELAHERE is right for you. It is not known if ELAHERE is safe and effective in children. IMPORTANT SAFETY INFORMATION What is the most important information I should know about ELAHERE? ELAHERE can cause serious side effects, including: Eye problems. Eye problems are common with ELAHERE and can also be severe. Tell your healthcare provider right away if you develop any eye problems during treatment with ELAHERE, including blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes. • Your healthcare provider will send you to see an eye care professional to check your eyes before you start treatment with ELAHERE, during treatment with ELAHERE, and as needed for any worsening signs and symptoms of eye problems. • Your healthcare provider will prescribe steroid eye drops and lubricating eye drops before you start and during your treatment with ELAHERE. You should use eye drops as directed by your healthcare provider. • Do not wear contact lenses throughout your treatment with ELAHERE unless you are told to use them by your healthcare provider. What should I tell my healthcare provider before receiving ELAHERE? Tell your healthcare provider about all of your medical conditions, including if you: • have vision or eye problems. • have numbness or tingling in your hands or feet. • have liver problems. • are pregnant or plan to become pregnant. ELAHERE can harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think you may be pregnant during treatment with ELAHERE. Patients who are able to become pregnant: • Your healthcare provider should do a pregnancy test before you start treatment with ELAHERE. • You should use an effective birth control (contraception) during treatment and for 7 months after your last dose of ELAHERE. • are breastfeeding or plan to breastfeed. It is not known if ELAHERE passes into your breast milk. Do not breastfeed during treatment and for 1 month after your last dose of ELAHERE. Tell your healthcare provider about all the medicines you take, including prescription and over the-counter medicines, vitamins, and herbal supplements. Taking certain other medicines during treatment with ELAHERE may cause side effects. What are the possible side effects of ELAHERE? ELAHERE can cause serious side effects, including: • Eye problems. Eye problems are common with ELAHERE and can also be severe. Tell your healthcare provider right away if you develop any eye problems during treatment with ELAHERE, including blurred vision, dry eyes, sensitivity to light, eye pain, eye redness, or new or worsening vision changes. • Lung problems (pneumonitis). ELAHERE can cause severe or life-threatening inflammation of the lungs that may lead to death. Tell your healthcare provider right away if you get new or worsening symptoms, including trouble breathing, shortness of breath, cough, or chest pain. • Peripheral neuropathy. Nerve problems called peripheral neuropathy are common during treatment with ELAHERE and can also be severe. Your healthcare provider will monitor you for signs and symptoms of nerve problems. Tell your healthcare provider if you get new or worsening numbness, tingling, burning sensation or pain in your hands or feet or muscle weakness. The most common side effects and abnormal labs of ELAHERE include: • increased liver enzymes in the blood • feeling tired • blurred vision • nausea • diarrhea • stomach-area (abdominal) pain • changes in the cornea (part of the eye) • peripheral neuropathy • muscle, bone, or joint pain • decreased red or white blood cell counts • decreased platelets • decreased magnesium level in the blood • dry eye • constipation • vomiting • decreased albumin level in the blood • decreased appetite Your healthcare provider may change your dose of ELAHERE, delay treatment, or completely stop treatment if you have certain side effects. These are not all of the possible side effects of ELAHERE. Call your doctor for medical advice about side effects. You are encouraged to report side effects of prescription drugs to the FDA. Visit or call 1‑800‑FDA‑1088. Please see Full Prescribing Information , including Boxed WARNING and Medication Guide About AbbVie in Oncology At AbbVie, we are committed to transforming standards of care for patients living with difficult-to-treat cancers. We are advancing a dynamic pipeline of investigational therapies across a range of cancer types in both blood cancers and solid tumors. We are focusing on creating targeted medicines that either impede the reproduction of cancer cells or enable their elimination. We achieve this through various, targeted treatment modalities including Antibody Drug Conjugates (ADCs), Immuno-Oncology, bi-specific antibody and CAR-T platforms. Our dedicated and experienced team joins forces with innovative partners to accelerate the delivery of potential breakthrough medicines. Today, our expansive oncology portfolio comprises of approved and investigational treatments for a wide range of blood and solid tumors. 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Additional information about the economic, competitive, governmental, technological and other factors that may affect AbbVie's operations is set forth in Item 1A, "Risk Factors," of AbbVie's 2022 Annual Report on Form 10-K, which has been filed with the Securities and Exchange Commission, as updated by its subsequent Quarterly Reports on Form 10-Q. AbbVie undertakes no obligation, and specifically declines, to release publicly any revisions to forward-looking statements as a result of subsequent events or developments, except as required by law. SOURCE AbbVie

Ovarian cancer patients whose disease develops resistance to platinum-based chemotherapies have few treatment alternatives. A new ovarian cancer drug that won a speedy FDA nod last fall now has data from a confirmatory study that clinicians say should support the drug’s full approval. They also say the new therapy, Elahere, will change the care of ovarian cancer. In Phase 3 results presented Sunday during the annual meeting of the American Society of Clinical Oncology in Chicago, Elahere shrunk tumors and helped ovarian cancer patients live longer compared to chemotherapies. But this drug, developed by Waltham, Massachusetts-based ImmunoGen, treats only patients whose tumors exhibit a particular biological marker. Elahere, known in development as mirvetuximab soravtansine, targets folate receptor alpha, a protein abundant on the surface of ovarian cancer cells. The drug is approved for treating patients whose expression of this protein is classified as high. The FDA approved a companion diagnostic from Roche Diagnostics that tests protein levels to determine a patient’s suitability for the ImmunoGen drug, an antibody drug conjugate comprised of a toxic payload directed to destination by a tumor-targeting antibody. The FDA’s accelerated approval for Elahere last November made it the first ADC approved for ovarian cancer. The last time the FDA approved a therapy for platinum-resistant ovarian cancer was in 2014, a decision that went to Roche’s Avastin. The main goal of the confirmatory Phase 3 test of Elahere was to measure progression-free survival, which is how long patients live without their disease worsening. Overall survival, measured from when patients were randomized in the study until death, was a secondary goal. The median follow-up with patients in this study 13.1 months. In 281 women who previously received Avastin, results showed progression-free survival with the ImmunoGen drug was 36% better and overall survival was 26% better in the Elahere arm compared to the physician’s choice of chemotherapy. In a group of 172 women who had not previously received Avastin, progression-free survival was 34% better and overall survival was 49% better in the study drug arm compared with the physician’s choice of chemo. Dr. Kathleen Moore, a University of Oklahoma professor of gynecologic oncology and the principal investigator of Elahere’s Phase 3 study, presented the results at the ASCO meeting. “These data are practice changing and position mirvetuximab as a new standard of care for patients with folate receptor alpha-positive platinum-resistant ovarian cancer,” she said. Elahere has already changed practice at City of Hope, said Dr. Thanh Dellinger, a gynecologic oncologist at the Duarte, California-based comprehensive cancer center. Since the drug’s accelerated approval, Dellinger used the drug in the treatment of patients who are folate receptor alpha positive high, she told MedCity News. Avastin and chemotherapies are “one-size fits all” treatments, but that approach doesn’t work for platinum-resistant ovarian cancer patients. While Elahere is the first ADC for ovarian cancer, it’s the second biomarker-driven therapy for the disease. Patients are tested for BRCA mutations to determine whether they are eligible for another type of targeted drug called a PARP inhibitor. Now they’ll also need to be tested for folate receptor alpha. “It’s another biomarker that we can use,” Dellinger said. “So ovarian cancer [treatment] has become much more biomarker driven.” Standard of care chemotherapies cause systemic toxic effects. The targeting ability of an ADC is intended to keep the therapy’s toxic effects concentrated on the tumors, sparing healthy tissue. On measures of safety, the adverse events in the Elahere Phase 3 study included low-grade eye and gastrointestinal problems, which is consistent with earlier studies. The drug’s label has a black box warning that alerts physicians and patients about the risk of eye problems including visual impairment; corneal damage; dry eye; sensitivity to light; pain; and uveitis, a type if inflammation inside the eye. Dellinger does not see the eye toxicity as a major problem, explaining that it can be managed with treatments such as steroid eye drops. She added that overall, the data reported at ASCO provide more information that she can use to counsel ovarian cancer patients. Dr. Merry Jennifer Markum, a chief of the division of hematology and oncology at the University of Florida College of Medicine and an ASCO expert, said that Elahere is “very promising” for becoming a first-line treatment for ovarian cancer. Patients and their physicians want to postpone toxic chemotherapies until they’re really needed. “Using a drug like this, that is better tolerated, allows us to perhaps go to this drug first and delay the toxic chemotherapy,” she said. In a note sent to investors Monday, William Blair analyst Andy Hsieh said that on the heels of Elahere’s positive Phase 3 data, the short-term focus now shifts to the drug’s commercialization. ImmunoGen reported $29.5 million in first quarter 2023 sales for Elahere, which far exceeded William Blair estimates. The Phase 3 data could catalyze a collaboration agreement in Europe, bringing the company more capital to extend its cash runway. Looking longer term, Hsieh noted that ImmunoGen is conducting additional clinical research that could support broadening the use of Elahere to more ovarian cancer patients and as part of combination therapies. The biotech is also developing a next-generation version of its drug that could address the spectrum of folate receptor alpha levels from low to high. Given the expression of this biomarker on other types of tumors, the drug may enable ImmunoGen to expand beyond ovarian cancer. ImmunoGen said it plans to file an application seeking full FDA approval of Elahere in the second half of this year. A submission seeking approval in Europe is expected in the same time frame.