New data from AbbVie’s innovative antibody-drug conjugate (ADC) platform will be showcased across three oral presentations at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting (May 31 – June 4, 2024).

AbbVie’s ADCs are designed to target unique protein biomarkers such as c-Met (MET protein) and SEZ6 (seizure-related homolog 6 protein), which are over-expressed across various tumor types. By utilizing these biomarkers as targets, ADCs are designed to deliver potent cancer cell death-inducing agents called ‘payloads’ to the tumor.

“Building upon our strong commitment to patients and existing leadership in hematological malignancies, we are rapidly advancing a differentiated pipeline in solid tumors,” said Daejin Abidoye, M.D., vice president, head of solid tumors, oncology development, AbbVie.

“Our ADC platform allows us to utilize selected biomarkers such as c-Met and SEZ6 to induce targeted cancer cell death by delivering potent anti-cancer agents. The data we are presenting at ASCO demonstrate the clinical potential of this approach across a wide range of difficult-to-treat tumors,” Abidoye further noted,

Clinical trials
Data from the dose-escalation and colorectal cancer (CRC) dose-expansion cohort of an ongoing first-in-human Phase 1 study (NCT05029882) of ABBV-400, a potential best-in-class c-Met directed ADC, will be presented in an oral presentation. The preliminary data show that among 122 heavily pre-treated advanced CRC patients, promising antitumor activity was observed at 2.4 and 3.0 mg/kg doses administered once every 3 weeks, with confirmed objective response rate (ORR) of 18% (n=40) and 24% (n=41) respectively in those groups. In patients with higher c-Met expression, ORR was enriched to >35% at doses ≥2.4 mg/kg. The most common Gr≥3 treatment-emergent adverse events (TEAEs) were anemia (35%), neutropenia (7%) and febrile neutropenia (6%). TEAEs leading to discontinuation occurred in 25 (20.5%) patients. Additional data will be presented at the meeting.

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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 CRC in combination with fluorouracil, folinic acid, and bevacizumab.

“c-Met overexpression, found in the majority of patients with metastatic CRC, has been reported to be associated with poor prognosis. However, there are no approved therapies specific for c-Met–overexpressing CRCs, making it an attractive cancer biomarker to target,” said Manish Sharma, M.D., Co-Director of Clinical Research at START Midwest (Grand Rapids, MI) and Principal Investigator on the ABBV-400 trial.

“Results from this Phase 1 study show preliminary evidence of efficacy for ABBV-400 in patients with heavily pre-treated colorectal cancer and are supportive of further exploration of this novel ADC in CRC and other solid tumors,” Sharma said.

In addition, early data from the monotherapy dose escalation part of a first-in-human study of ABBV-706, a potential best-in-class SEZ6 directed ADC, will be presented at an oral presentation. The data demonstrate that among a total of 48 efficacy-evaluable patients (23 SCLC and 25 NEN), the overall confirmed objective response rate was 43.8%. Within the SCLC group, the confirmed objective response rate was 60.9%. Among all the 53 enrolled patients at the time of data cut-off, the most common ≥3 TEAEs were neutropenia (42%), anemia (42%), and leukopenia (28%).

The ongoing study (NCT05599984) is evaluating ABBV-706 as monotherapy or in combination with budigalimab (a programmed cell death 1 inhibitor), carboplatin, or cisplatin, in patients with advanced solid tumors, including SCLC and other NENs. Additional data will be presented at the meeting.

Topoisomerase 1 inhibitor
Both ABBV-400 and ABBV-706 utilize a novel, AbbVie proprietary topoisomerase 1 inhibitor (Top1i) payload. Top1i is an anticancer agent that induces cell death by interrupting DNA replication. ABBV-400 and ABBV-706 are designed to specifically deliver Top1i to cells expressing c-Met and SEZ6 respectively.

AbbVie will also present data from the primary analysis of the Phase 2 LUMINOSITY non-small cell lung cancer (NSCLC) trial evaluating telisotuzumab vedotin (Teliso-V), a potential first-in-class c-Met directed ADC utilizing a microtubule polymerization inhibitor, monomethyl auristatin E (MMAE) payload, in patients with previously treated c-Met-overexpressing, non-squamous, epidermal growth factor receptor (EGFR) wild type, advanced NSCLC.

AbbVie previously announced positive topline results from the study in November 2023.

Other presentations from AbbVie’s ADC platform include safety and efficacy data in an older population (≥ 65) from the Phase 3 MIRASOL trial of mirvetuximab soravtansine (Elahere®; AbbVie) (MIRV) vs investigator’s choice chemotherapy in patients with platinum-resistant ovarian cancer (PROC) and high folate receptor-alpha (FRα) expression, and a retrospective, exploratory pooled analysis characterizing long-term survivors from four clinical trials examining patients with folate receptor alpha-positive recurrent ovarian cancer treated with MIRV monotherapy.

Oral presentations at ASCO are available below:

Title

Date/Time

Session

Abstract number

First-in-human study of ABBV-706, a
seizure-related homolog protein 6
(SEZ6)–targeting antibody-drug
conjugate (ADC), in patients (pts) with
advanced solid tumors.

1 June,
3:12 PM
CDT

Developmental
Therapeutics—
Molecularly Targeted
Agents and Tumor
Biology

Oral Abstract Session

Abstract:
3001

Telisotuzumab vedotin monotherapy in
patients with previously treated c-Met–
overexpressing non-
squamous EGFR wildtype advanced
NSCLC: Primary analysis of the
LUMINOSITY trial.

2 June,
10:01 AM CDT

Next-Generation
Antibody–Drug
Conjugates: The
Revolution Continues

Clinical Science
Symposium

Abstract: 103

First-in-human study of ABBV-400, a
novel c-Met–targeting antibody-drug
conjugate, in advanced solid tumors:
Results in colorectal cancer.

3 June,
2:15 PM
CDT

Gastrointestinal
Cancer—Colorectal and
Anal

Rapid Oral Abstract
Session

Abstract:
3515

 

Clinical trials
Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Advanced Solid Tumors Receiving Intravenous (IV) ABBV-400 as Monotherapy and in Combination With IV Bevacizumab – ClinicalTrials.gov ID NCT05029882;
Study to Assess Adverse Events and Change in Disease Activity in Adult Participants With Select Advanced Solid Tumor Indications Receiving Intravenous (IV) ABBV-400 – ClinicalTrials.gov ID – NCT06084481
Study to Assess Adverse Events and Change in Disease Activity in Previously Treated Adult Participants Receiving Intravenous (IV) ABBV-400 With Unresectable Metastatic Colorectal Cancer in Combination With IV Fluorouracil, Folinic Acid, and Bevacizumab – ClinicalTrials.gov ID – NCT06107413
Study to Evaluate Adverse Events, Change in Disease Activity, and How ABBV-706 Moves Through the Body When Intravenously (IV) Infused Alone or in Combination With IV Infused Budigalimab, Cisplatin, or Carboplatin in Adult Participants With Advanced Solid Tumors – ClinicalTrials.gov ID – NCT05599984

Highlights of prescribing information
mirvetuximab soravtansine (Elahere®; AbbVie) [Prescribing Information]

Featured image: AbbVie booth at the 2019 annual meeting of the American Society of Clinical Oncology (ASCO) held June 1 – 4, 2019 in Chicago, Ill.

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