AbbVie ABBV

• Full data from the primary analysis of the positive, single-arm Phase 2 PICCOLO trial, evaluating mirvetuximab soravtansine (ELAHERE®), for high folate receptor-alpha (FRα) expressing platinum-sensitive ovarian cancer (PSOC) (mini-oral presentation).
• Exploratory patient reported outcomes (PROs) from the Phase 2 LUMINOSITY trial, evaluating telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed antibody-drug conjugate (ADC), in advanced non-small cell lung cancer (NSCLC).
• New safety and efficacy data in pre-treated patients with advanced NSCLC (mini-oral presentation) and gastroesophageal cancer (GEA), from a Phase 1 study of telisotuzumab adizutecan (ABBV-400), a next-generation, potential best-in-class c-Met directed ADC.

NORTH CHICAGO, Ill., Sept. 9, 2024 /PRNewswire/ -- AbbVie (NYSE: ABBV) today announced that new data from its innovative antibody-drug conjugate (ADC) platform will be showcased at the upcoming European Society for Medical Oncology (ESMO) Congress 2024 (September 13-17, 2024). Presentations include data on mirvetuximab soravtansine (ELAHERE®) and c-Met targeting ADCs, telisotuzumab vedotin (Teliso-V) and telisotuzumab adizutecan (ABBV-400). AbbVie's ADCs are designed to target protein biomarkers such as folate receptor-alpha (FRα) and c-Met (MET protein) which are over expressed across various tumor types and are associated with poor prognoses.^1-9 The ADCs are designed to deliver potent cancer cell-death inducing agents called 'payloads' specifically to the tumor, by utilizing these biomarkers as targets.

Data from the primary analysis of the Phase 2 PICCOLO trial evaluating investigational mirvetuximab soravtansine monotherapy in heavily pre-treated patients with FRα positive, platinum-sensitive ovarian cancer (PSOC) showed that the trial met its primary endpoint with an objective response rate (ORR) of 51.9% (95% CI 40.4, 63.3), including 6 complete and 35 partial responses. Among the 79 enrolled patients, 81% had prior poly (ADP-ribose) polymerase inhibitors (PARPi) treatment; 74.7% of whom progressed while on PARPi. The median duration of response (DOR), a key secondary endpoint, was 8.3 months (95% CI 5.5, 10.8) and median progression-free survival (PFS), an additional secondary endpoint, was 6.9 months (95% CI 5.9, 9.6). The safety profile of mirvetuximab soravtansine was consistent with findings from previous studies, and no new safety concerns were identified. The most common treatment-emergent adverse events (TEAEs) (grade ≥ 3) were blurred vision (10%), dry eye (3%), nausea (1%), keratopathy (4%), and diarrhea (3%). Additional data will be presented at the meeting.

"There is an urgent patient-driven unmet need to identify novel, effective and tolerable therapies for patients with platinum-sensitive ovarian cancer, including the PARPi pre-treated setting where diminished response to subsequent platinum-based chemotherapy has been reported," said Angeles Alvarez Secord, M.D., M.H.Sc., from the Duke Cancer Institute. "The response rate seen with mirvetuximab soravtansine in PICCOLO highlights the potential of mirvetuximab soravtansine for platinum-sensitive ovarian cancer patients."

Mirvetuximab soravtansine is also being studied in PSOC in the Phase 3 GLORIOSA trial (NCT05445778), in combination with bevacizumab versus bevacizumab alone, in maintenance after second-line platinum-doublet therapy. Additionally, a Phase 2 study IMGN853-0420 (NCT05456685), is investigating the combination of mirvetuximab soravtansine with carboplatin as second-line treatment of PSOC with a wider range of FRα expression.

Patient reported outcome (PRO) data from the Phase 2 LUMINOSITY trial of Teliso-V, in c-Met protein overexpressing, epidermal growth factor receptor (EGFR) wild type, advanced/metastatic non-squamous non-small cell lung cancer (NSCLC) patients, will be presented at the meeting. Trends in PROs observed in LUMINOSITY will be further evaluated in the ongoing Phase 3 TeliMET NSCLC-01 trial (NCT04928846).

"The data at ESMO showcase the depth of our ADC pipeline and highlights the significant progress we are making across key programs in various stages of development, as we strive to deliver new and innovative medicines for patients in need," said Daejin Abidoye, M.D., vice president, head of solid tumors, oncology development, AbbVie. "A testament to these efforts is our plan to submit Teliso-V for accelerated approval as a monotherapy in patients with previously treated c-Met overexpressing, epidermal growth factor receptor (EGFR) wild-type non-squamous non-small cell lung cancer in Q3 2024."

The accelerated approval submission for Teliso-V will be reviewed under FDA's real-time oncology review program with an approval decision anticipated in 2025. AbbVie announced FDA breakthrough therapy designation for Teliso-V in 2022.

New safety and efficacy data from a Phase 1 study (NCT05029882) of ABBV-400, a next-generation, potential best-in-class c-Met directed ADC, highlights the potential of ABBV-400 in previously-treated NSCLC and gastroesophageal cancer (GEA) patients, and are supportive of further exploration of this novel ADC in these tumor types and other solid tumors:

• Preliminary data show that among 48 previously treated EGFR wild type non-squamous NSCLC patients, antitumor activity was observed with ABBV-400 when dosed at 2.4 and 3.0 mg/kg administered once every 3 weeks (n=39 and 9, respectively), with a confirmed ORR of 43.8% and clinical benefit rate of 85.4%. The most common (≥10%) TEAEs (grade ≥ 3) were anemia (25%) and neutropenia (15%). Additional endpoints (such as progression free survival), association between c-Met protein expression and treatment response, and detailed safety data will be presented at the meeting.
• In GEA patients, the preliminary data show that among 42 patients, antitumor activity was observed at a dose of ABBV-400 of 3.0 mg/kg administered once every 3 weeks, with confirmed ORR of 28.6%. The clinical benefit rate was 71.4%. The most common (≥20%) TEAEs (any grade) were gastrointestinal (76.2%), anemia (66.7%), nausea (47.6%), thrombocytopenia and constipation (26.2% each) and neutropenia (23.8%). Additional safety and efficacy data will be presented at the meeting.

ABBV-400 is also being evaluated in a Phase 1b basket study (NCT06084481) in advanced solid tumors as a monotherapy and a Phase 2 study (NCT06107413) in second line metastatic colorectal cancer (CRC) in combination with fluorouracil, folinic acid, and bevacizumab.

Teliso-V and ABBV-400 both target c-Met with the same parental antibody but have different designs and mechanisms of action.^10,11 Teliso-V, AbbVie's most advanced c-Met targeted ADC in development, utilizes a microtubule polymerization inhibitor (MMAE) payload.¹⁰ ABBV-400, a next-generation c-Met targeted ADC utilizes a novel, proprietary topoisomerase 1 inhibitor (Top1i) payload.¹¹ 

AbbVie will also present real-world data on the prevalence, stability, and prognostic value of c-Met protein overexpression in NSCLC from the METPRO and METEXPRESS studies at the meeting.

Further information on AbbVie clinical trials is available at https://www.clinicaltrials.gov/. 

Additional details on key presentations at ESMO are available below:

About the PICCOLO trial
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.

AbbVie previously announced positive topline results from the study in June 2024.

About the LUMINOSITY trial
The LUMINOSITY trial (M14-239), is an ongoing single-arm Phase 2 study designed to identify the target NSCLC populations that overexpress c-Met best suited for Teliso-V monotherapy in the second line or third line setting, and then to expand the groups to further evaluate efficacy in the selected populations. The endpoints include overall response rate (ORR), duration of response (DoR), disease control rate (DCR) and progression-free survival (PFS) per independent central review (ICR) as well as overall survival (OS). AbbVie previously announced positive topline results from the LUMINOSITY study in November 2023.

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.

The Marketing Authorization Application (MAA) for mirvetuximab soravtansine in Europe has been accepted by the European Medicines Agency (EMA) and regulatory submissions 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. INDICATION and IMPORTANT SAFETY INFORMATION
ELAHERE® is indicated for the treatment of adult patients 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.

IMPORTANT SAFETY INFORMATION

WARNING: OCULAR TOXICITY

• ELAHERE can cause severe ocular toxicities, including visual impairment, keratopathy, dry eye, photophobia, eye pain, and uveitis.
• Conduct an ophthalmic exam including visual acuity and slit lamp exam prior to initiation of ELAHERE, every other cycle for the first 8 cycles, and as clinically indicated.
• Administer prophylactic artificial tears and ophthalmic topical steroids.
• Withhold ELAHERE for ocular toxicities until improvement and resume at the same or reduced dose.
• Discontinue ELAHERE for Grade 4 ocular toxicities.

WARNINGS and PRECAUTIONS
Ocular Disorders

ELAHERE can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.

Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with ELAHERE. Eleven percent (11%) of patients experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract). The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%). 

The median time to onset for first ocular adverse reaction was 5.1 weeks (range: 0.1 to 68.6). Of the patients who experienced ocular events, 53% had complete resolution; 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to permanent discontinuation of ELAHERE in 1% of patients. 

Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with ELAHERE are recommended. Advise patients to avoid use of contact lenses during treatment with ELAHERE unless directed by a healthcare provider. 

Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated. Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.

Monitor for ocular toxicity and withhold, reduce, or permanently discontinue ELAHERE based on severity and persistence of ocular adverse reactions.

Pneumonitis

Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with ELAHERE.

Pneumonitis occurred in 10% of patients treated with ELAHERE, including 1% with Grade 3 events and 1 patient (0.1%) with a Grade 4 event. One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases. One patient (0.1%) died due to respiratory failure of unknown etiology. Pneumonitis led to permanent discontinuation of ELAHERE in 3% of patients.

Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Withhold ELAHERE for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤ Grade 1 and consider dose reduction. Permanently discontinue ELAHERE in all patients with Grade 3 or 4 pneumonitis. Patients who are asymptomatic may continue dosing of ELAHERE with close monitoring.

Peripheral Neuropathy (PN)

Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with ELAHERE across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy. Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%). Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia. For patients experiencing new or worsening PN, withhold dosage, dose reduce, or permanently discontinue ELAHERE based on the severity of PN.

Embryo-Fetal Toxicity

Based on its mechanism of action, ELAHERE can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with ELAHERE and for 7 months after the last dose.

ADVERSE REACTIONS

The most common (≥20 %) adverse reactions, including lab abnormalities, were increased aspartate aminotransferase, fatigue, increased alanine aminotransferase, blurred vision, nausea, increased alkaline phosphatase, diarrhea, abdominal pain, keratopathy, peripheral neuropathy, musculoskeletal pain, decreased lymphocytes, decreased platelets, decreased magnesium, decreased hemoglobin, dry eye, constipation, decreased leukocytes, vomiting, decreased albumin, decreased appetite, and decreased neutrophils.

DRUG INTERACTIONS

DM4 is a CYP3A4 substrate. Closely monitor patients for adverse reactions with ELAHERE when used concomitantly with strong CYP3A4 inhibitors. 

USE IN SPECIAL POPULATIONS

Lactation
Advise women not to breastfeed during treatment with ELAHERE and for 1 month after the last dose.

Hepatic Impairment
Avoid use of ELAHERE in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).

Please see full Prescribing Information, including BOXED WARNING

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. We are evaluating more than 20 investigational medicines in multiple clinical trials across some of the world's most widespread and debilitating cancers. As we work to have a remarkable impact on people's lives, we are committed to exploring solutions to help patients obtain access to our cancer medicines. For more information, please visit http://www.abbvie.com/oncology.

About AbbVie
AbbVie's mission is to discover and deliver innovative medicines and solutions that solve serious health issues today and address the medical challenges of tomorrow. We strive to have a remarkable impact on people's lives across several key therapeutic areas – immunology, oncology, neuroscience, and eye care – and products and services in our Allergan Aesthetics portfolio. For more information about AbbVie, please visit us at www.abbvie.com. Follow @abbvie on LinkedIn, Facebook, Instagram, X (formerly Twitter), and YouTube.

Forward-Looking Statements
Some statements in this news release are, or may be considered, forward-looking statements for purposes of the Private Securities Litigation Reform Act of 1995. The words "believe," "expect," "anticipate," "project" and similar expressions and uses of future or conditional verbs, generally identify forward-looking statements. AbbVie cautions that these forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those expressed or implied in the forward-looking statements. Such risks and uncertainties include, but are not limited to, challenges to intellectual property, competition from other products, difficulties inherent in the research and development process, adverse litigation or government action, and changes to laws and regulations applicable to our industry. 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 2023 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.  

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