ASCO: AbbVie revamps ADC assets after Rova-T failure

At this year’s American Society of Clinical Oncology (ASCO) conference, a significant trend has emerged: the potential for replacing long-standing chemotherapy treatments with innovative therapies. AbbVie is keen to be part of this transformation. AbbVie’s vice president of solid tumor pipeline strategy and execution, Pedro Valencia, Ph.D., stated, “This is the ASCO where we show the most antibody-drug conjugate (ADC) data in history for AbbVie.”

Daejin Abidoye, M.D., head of solid tumors, oncology development, emphasized the growing importance of ADCs in treating solid tumors. “You look back five years ago, ADCs were primarily in the hematology space. Now you're seeing ADCs playing a significant role in solid tumors. If there is one takeaway, it’s that we expect that over time there will be therapies available for patients that do not include chemotherapy," Abidoye said.

AbbVie presented key results from a phase 2 study called Luminosity, which evaluated their next-generation ADC, telisotuzumab vedotin (Teliso-V), for non-small cell lung cancer (NSCLC). This ADC is a combination of the monoclonal antibody telisotuzumab and the microtubule polymerization inhibitor monomethyl auristatin E. Among 161 patients with previously treated c-Met–overexpressing non-squamous EGFR wildtype advanced NSCLC, the overall response rate (ORR) was 28.6%.

Abidoye remarked, “We're pretty encouraged by what we've seen thus far in terms of response rate, durability of those responses, and the overall safety profile.” Historically, the ORR for chemotherapy docetaxel is about 15% to 20%, or slightly higher when combined with monoclonal antibody ramucirumab. In the phase 2 ADC trial, patients with high c-Met expression had a higher ORR of 34.6%, compared to 22.9% for those with intermediate c-Met expression.

However, the data also showed a decrease in response rates compared to previous updates. In 2022, the study linked Teliso-V to response rates of 53.8% for c-Met high patients and 25% for c-Met intermediate patients. Additionally, there were two treatment-related deaths in the trial—one from interstitial lung disease (ILD) and another from respiratory failure. Abidoye noted the concern regarding ILD, particularly in ADCs evaluated for non-small cell lung cancer. AbbVie has established an ILD adjudication team to better understand these cases.

AbbVie will continue exploring the ADC’s safety profile in an ongoing phase 3 trial involving 700 patients with c-Met overexpressing, previously treated NSCLC. This study will compare Teliso-V to docetaxel, with primary results expected in mid-2025. AbbVie plans to seek accelerated FDA approval for Teliso-V, although further comments are currently unavailable.

Beyond Teliso-V, AbbVie shared early data from other ADC programs. This includes a phase 1 trial investigating ABBV-706, a SEZ6-directed ADC, for advanced solid tumors. Additionally, AbbVie presented early findings from a phase 1 dose-escalation and colorectal cancer dose-expansion cohort of ABBV-400, another investigational c-Met directed ADC.

AbbVie’s current ADC efforts follow the failure of Rova-T, an ADC acquired in a $5.8 billion buyout of Stemcentrx eight years ago. The discontinuation of Rova-T, due to poor efficacy in lung cancer trials, provided valuable lessons for AbbVie. Valencia highlighted that the Stemcentrx platform used different payloads and antibodies. He noted, “We've spent a lot of time trying to find a combination of target linkers, payloads, that maximizes the therapeutic interface. You have to hit the right dose before it gets too toxic.”

The new generation of ADCs from AbbVie aims to be more refined, with stable linkers and optimized drug-antibody ratios to enhance efficiency. These advancements underscore AbbVie’s commitment to developing innovative treatments that may one day replace traditional chemotherapy.