ASCO 2023: A Quick Preview on Antibody-drug Conjugate Abstracts

ENHERTU (trastuzumab deruxtecan) is an engineered HER2-directed antibody-drug conjugate (ADC) jointly developed and commercialized by AstraZeneca and Japanese drugmaker Daiichi Sankyo.

The DESTINY-PanTumor02 Phase II trial investigates the effectiveness of ENHERTU in patients with advanced, inoperable, or metastatic HER2-positive solid tumors, encompassing a wide range of cancer types such as biliary tract, bladder, cervical, endometrial, ovarian, pancreatic, and rare tumors. These individuals, who are ineligible for curative interventions, represent a critical population for this study.

ENHERTU has already showcased its ability to enhance patient outcomes in breast, gastric, and lung cancers by targeting the HER2 receptor. The company has expressed optimism regarding these promising initial findings, which highlight the potential of ENHERTU to address critical gaps in treatment for other tumor types with urgent unmet needs.

According to AstraZeneca, the safety profile of ENHERTU observed in the Phase II trial aligns with previous studies, with no new safety concerns identified. The companies mentioned their intention to share the data with regulatory agencies worldwide and present it at an upcoming ASCO annual meeting.

In September of last year, the FDA granted clearance for Eli Lilly's RETEVMO to be used in adult patients with locally advanced or metastatic solid tumors that have a specific genetic alteration called RET fusion. Additionally, the FDA approved Novartis' combination therapy of TAFINLAR and MEKINIST for both adult and pediatric patients with unresectable or metastatic solid tumors harboring a specific genetic mutation known as BRAF V600E.

ENHERTU achieves its effect by specifically targeting tumors that express HER2 and delivering a potent treatment. This antibody-drug conjugate, designed to target HER2, has shown remarkable effectiveness, leading to FDA approvals for HER2-positive breast cancer, non-small cell lung cancer, and gastric cancer.

Conclusion: The significant and meaningful responses observed in the DESTINY-PanTumor02 trial will strengthen the confidence in ENHERTU's potential for treating various types of cancers that express HER2. The promising results obtained across multiple groups within the trial will guide the future plans of AstraZeneca and Daiichi Sankyo in their comprehensive development program, aiming to make ENHERTU available to a wide range of patients expeditiously.

Abstract Number – LBA5507

Title: Will MIRASOL data favor - ImmunoGen’s plan to submit a Marketing Authorization Application in Europe and a supplemental Biologics License Application in the US for the conversion to a regular approval of ELAHERE in FRα-positive platinum-resistant ovarian cancer?

Commentary- Results from the late-stage study, dubbed MIRASOL, evaluating ELAHERE versus investigator's choice (IC) of single-agent chemotherapy (weekly paclitaxel, pegylated liposomal doxorubicin or topotecan) to treat patients with platinum-resistant ovarian cancer whose tumors express high levels of FRα, and who have received up to three prior regimens will be presented at the ASCO annual meeting.

Executive Summary – Results from the Phase III confirmatory MIRASOL trial (GOG 3045/ENGOT OV-55) evaluating the safety and efficacy of ELAHERE (mirvetuximab soravtansine-gynx) compared to chemotherapy in patients with folate receptor alpha (FRα)-positive platinum-resistant ovarian cancer, have been selected for a late-breaking oral presentation at the 2023  ASCO Annual Meeting.

Main Content – The MIRASOL trial, a Phase III confirmatory study, aims to assess the safety and effectiveness of ELAHERE (mirvetuximab soravtansine-gynx) in comparison to chemotherapy for patients with platinum-resistant ovarian cancer who have received one to three prior treatment regimens. The study specifically targets patients with folate receptor alpha (FRα)-positive tumors.

The outcomes of the MIRASOL trial carry great importance beyond mere statistical data. For patients, these results hold the potential for extended periods of disease control, enhanced well-being, and potentially increased survival rates. Considering that these patients have already undergone up to three previous treatment regimens, including platinum-based therapies, the demand for innovative treatments like ELAHERE is pressing and imperative.

Drawing from the trial data, the company intends to submit applications for marketing authorization in Europe and a supplemental biologics license in the US to transition ELAHERE from its current status to regular approval in the latter half of 2023. These data will serve as the basis for strengthening ImmunoGen's commitment to the clinical development program and expanding the use of this therapy in broader patient populations, including those with platinum-sensitive diseases.

As major pharmaceutical companies like Mersana Therapeutics, Eisai, and Sutro BioPharma are also developing clinical-stage ADCs to target platinum-resistant ovarian cancer, ImmunoGen's ELAHERE might face tough competition and potentially be overshadowed.

Conclusion: The latest findings from the MIRASOL trial have the potential to revolutionize ImmunoGen's ELAHERE, establishing it as a groundbreaking therapy for platinum-resistant ovarian cancer. These results will not only validate the previously observed clinical advantages seen in the SORAYA trial, resulting in accelerated approval but also set the stage for obtaining full FDA approval.

Abstract Number – 3024, 3082, and 3002

Title: First in human data of ITGB6, CLDN6, and SEZ6 targeting ADCs

Commentary- At the ASCO annual meeting data from first-in-human studies of antibody-drug conjugates targeting ITGB6, CLDN6, and SEZ6 will be presented.

Executive Summary – Key players such as Seagen, AbbVie, and TORL BioTherapeutics are poised to unveil the outcomes of their respective ADCs at the upcoming ASCO conference.

Main Content – Starting with SGN-B6A, a fully owned ADC developed to target integrin beta-6 (ITGB6). ITGB6, a receptor involved in tumor development and invasiveness, is often overexpressed in cancers associated with poor outcomes, including non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and esophageal cancer (EC). SGN-B6A exhibits potent antitumor effects through mechanisms such as MMAE-mediated cytotoxicity, bystander effect, and immunogenic cell death. Updated findings from a Phase I study (SGNB6A-001) evaluating SGN-B6A in patients with advanced solid tumors, with a specific focus on NSCLC, HNSCC, and EC, will be presented at the upcoming annual meeting. Seagen previously disclosed Phase I clinical data in November last year at the Society for Immunotherapy of Cancer’s (SITC) Annual Meeting. The initial results demonstrated a manageable safety profile at the explored dosage regimens, along with promising antitumor activity in heavily treated patients with advanced solid tumors, leading to the expansion of patient cohorts in NSCLC, HNSCC, and EC.

AbbVie is also set to present initial findings from the dose escalation and expansion cohorts of the groundbreaking ABBV-011 study during the upcoming meeting. ABBV-011, an ADC, is designed to specifically target SEZ6 using a calicheamicin payload. Promising antitumor activity has been observed in preclinical models of small-cell lung cancer (SCLC). Given the poor prognosis associated with SCLC and the pressing need for new treatments, SEZ6, a transmembrane protein expressed in SCLC tumors, emerges as a potential therapeutic target.

In addition, TORL BioTherapeutics, a recently established US company dedicated to developing innovative antibody-based treatments for cancer patients, will be unveiling the preliminary findings from the dose-finding phase of their groundbreaking Phase I study. The study focuses on a novel ADC called TORL-1-23, which specifically targets Claudin 6 (CLDN6), and its effects on patients with advanced solid tumors. These exciting results will be presented at the upcoming meeting.

Conclusion: The field of ADCs is entering a transformative phase, with increasing novel targets and applications. This emerging form of targeted cancer therapy holds great promise and is anticipated to replace traditional chemotherapy in the future.