This year, the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting will feature a breadth of new data on emerging antibody-drug conjugates (ADCs) and T-cell engagers (TCEs), particularly across solid tumors and hematologic malignancies. This article synthesizes pivotal findings from AbbVie’s next-generation ADC and TCE platforms—including SEZ6-, PSMA/STEAP1-, c-Met-, and FRα-targeted ADCs—alongside immune checkpoint inhibitor combinations and real-world evidence.
Cancer’s biological complexity requires innovative therapies targeting both tumor cell-intrinsic and microenvironmental drivers. ADCs and TCEs exemplify this approach, bridging potent cytotoxic agents or immunomodulation with tumor-specific targeting.
Recent clinical trials and real-world data signal expanding roles for these modalities, particularly in traditionally hard-to-treat malignancies.
c-Met–Targeted ADCs – Telisotuzumab Adizutecan (Temab-A, ABBV-400)
Non-Small Cell Lung Cancer (NSCLC):
First-Line Combination (Temab-A + Osimertinib): Telisotuzumab adizutecan, a c-Met–targeted ADC conjugated to a topoisomerase I inhibitor payload, is being studied in combination with osimertinib (Tagrisso®; AstraZeneca) for previously untreated, EGFR-mutated, unresectable/metastatic NSCLC. The phase 2/3 trial (NCT05029882) randomizes patients to combination therapy or osimertinib alone, stratified by c-Met expression and CNS involvement. Primary phase 2 endpoints are safety, tolerability, and objective response rate (ORR). The phase 3 part of the study will compare the combination to the standard of care, with details to be finalized after phase 2 completion. This approach aims to address resistance and improve outcomes beyond osimertinib monotherapy. (Abstract TPS8663)[1]
Second-Line and Beyond (AndroMETa-Lung-713): AndroMETa-Lung-713 (NCT07155187) is a phase 2/3 study of telisotuzumab adizutecan versus investigator ’s-choice standard of care (SOC) in EGFR-mutated NSCLC after progression on EGFR-TKIs. In a prior first-in-human (FIH) trial, telisotuzumab adizutecan monotherapy yielded a 63% ORR, a median response duration of 9.8 months, and a median progression-free survival (PFS) of 10.9 months, supporting further investigation in this setting and in biomarker-defined populations. (Abstract TPS8661) [2]
Platinum-Resistant Ovarian Cancer (PROC) & Head and Neck Squamous Cell Carcinoma (HNSCC):
- Phase 1 basket studies (NCT06084481) demonstrated antitumor activity as monotherapy in PROC and HNSCC, including 21% ORR and a median PFS of 4.3 months in HNSCC, with a manageable safety profile. These new data support the potential of telisotuzumab adizutecan across an expanding range of solid tumors and patient populations, including previously presented data in lung, colorectal, and gastric cancers, as well as in patients with MET amplification and increased c-Met expression. (Abstracts 5514, 6027)[3]
MET-Amplified Solid Tumors:
- A phase 2 study (NCT07196644) is evaluating telisotuzumab adizutecan in advanced solid tumors with MET amplification, a poor-prognosis subgroup for which no approved targeted therapies exist. In contrast to c-MET tyrosine kinase inhibitors, telisotuzumab adituzumab does not inhibit c-MET signaling; instead, it targets the receptor, enabling direct delivery of the payload to the target cell while sparing healthy or normal tissues.
Telisotuzumab Vedotin (Teliso-V; ABBV-399; Emrelis®):
NSCLC (LUMINOSITY Study):
- Telisotuzumab Vedotin is an ADC and microtubule inhibitor conjugate, for adult patients with locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC) with high c-Met protein overexpression [≥50% of tumor cells with strong (3+) staining], as determined by a US Food and Drug Administration (FDA)-approved test (VENTANA MET (SP44) RxDx Assay (Roche Diagnostics) who have received a prior systemic therapy. In May 2025, the US Food and Drug Administration granted accelerated approval. Exploratory analysis from the phase 2 LUMINOSITY trial (NCT03539536) showed that MET amplification (amp) is more common in high c-Met overexpression (45%) versus intermediate overexpression (22%). Telisotuzumab vedotin demonstrated clinical activity regardless of MET amp status. In patients with MET amplification and high c-Met overexpression, the overall response rate (ORR) ranged from 31–57%, with a median PFS of up to 8 months. No new safety signals were observed. Ongoing phase 3 trials will further define predictive biomarkers for response. [4]
SEZ6–Targeted ADCs: ABBV-706
Small Cell Lung Cancer (SCLC):
- Small cell lung cancer (SCLC) is characterized by aggressive and rapid growth with poor prognosis, limited treatment options, and a tendency to develop early spread to distant sites, including mediastinal lymph nodes, liver, bones, adrenal glands, and brain. The SEZanne phase 2 global, open-label, randomized study (NCT07155174) is evaluating ABBV-706, a seizure-related homolog 6 (SEZ6)-directed ADC with a topoisomerase 1 inhibitor payload, plus atezolizumab (PD-L1 inhibitor), versus SOC (platinum/etoposide/atezo) as first-line therapy for extensive-stage SCLC. SEZ6 is a neuroendocrine marker highly expressed in SCLC. The study includes a safety lead-in and dose optimization, with primary endpoints of safety, tolerability, and PFS. Efficacy, duration of response, and OS are secondary endpoints. This trial addresses the need for more durable responses beyond platinum-based regimens. The study is enrolling, with dose-optimization and safety as primary goals. (Abstract TPS8135) [5]
- Relapsed/Refractory SCLC (Phase 1 and Combination with Budigalimab; ABBV-181): In a phase 1 study (NCT05599984), ABBV-706 monotherapy showed a 52% ORR overall, with 82% ORR at the phase 3 dose (1.8 mg/kg) as second-line therapy. Median response duration was up to 6.7 months, and median OS ranged from 11.3 to 14.3 months depending on the line of therapy. Combination with budigalimab (anti-PD-1) was feasible, offering a promising OS benefit in a heavily pretreated population of patients with R/R SCLC, with a 55% ORR, a median PFS of 8.1 months, and no new safety signals. (Abstract 8008)[6]
Central Nervous System (CNS) Tumors:
- In a phase 1, first-in-human study (NCT05599984), ABBV-706 was evaluated in high-grade CNS tumors (advanced relapsed/refractory glioblastoma; IDH-wildtype, Grade 4) or astrocytoma; IDH-mutant, G 3/4). Among 41 patients with GBM treated at 2.5 mg/kg, confirmed ORR was 10%, with two complete responses. Median PFS was 2.7 months, and median OS was 6.4 months. The safety profile was consistent with other tumor types. (Abstract 2041)[7]
PSMA/STEAP1–Targeted ADCs: ABBV-969: Metastatic Castration-Resistant Prostate Cancer (mCRPC):
- Prostate cancer has the second-highest incidence rate and is the fifth leading cause of cancer-related deaths among men worldwide. A phase 1, first-in-human dose escalation study (NCT06318273) of ABBV-969—a dual Prostate-specific membrane antigen (PSMA) and six-transmembrane epithelial antigen of prostate 1 (STEAP1)-targeting ADC with a topoisomerase 1 inhibitor payload—in 49 heavily pretreated mCRPC patients showed a confirmed ORR of 45% (n=29 RECIST-evaluable). PSA50 and PSA90 responses (≥3 mg/kg) were 67% and 28%, respectively. Grade ≥3 adverse events occurred in 63% of patients, primarily anemia. ABBV-969 demonstrated promising antitumor activity. Dose optimization is ongoing, and the safety profile was considered manageable. (Abstract 5014)[8]
Folate Receptor-Alpha (FRα)–Targeted ADCs
Mirvetuximab Soravtansine (IMGN-853; Elahere®): Platinum-Resistant Ovarian Cancer (PROC):
- Real-world (RW) outcomes from a retrospective US cohort of 129 mirvetuximab soravtansine-treated and 342 single-agent chemotherapy (CTx)–treated Platinum-Resistant Ovarian Cancer (PROC-) patients showed that mirvetuximab soravtansine provided a median PFS of 5.65 months versus 3.38 months for CTx, consistent with the phase 3 MIRASOL trial (NCT04209855; completed). Real World mOS for CTx was 7.59 months; data for mirvetuximab soravtansine were not yet mature. Safety findings were consistent with prior reports, supporting the generalizability of mirvetuximab soravtansine’s efficacy and tolerability to broader clinical practice. The study outcome confirmed that, in a real-world setting, mirvetuximab soravtansine monotherapy in platinum-resistant ovarian cancer was comparable to the progression-free survival (PFS) data observed in the MIRASOL study. (Abstract e17606) [9]
T-cell Engagers
Etentamig (BCMAxCD3 Bispecific Antibody; ABBV-383): Relapsed/Refractory Multiple Myeloma:
- Etentamig (ABBV-383; a bivalently BCMA-binding, low-affinity CD3 TCE) is an investigational, second-generation differentiated bispecific antibody designed to treat relapsed or refractory multiple myeloma and AL amyloidosis (immunoglobulin light chain amyloidosis), a rare disease in which abnormal bone marrow plasma cells produce misfolded protein ‘light chains.’ These misfolded proteins clump into amyloid deposits and build up in tissues and vital organs—including the heart, kidneys, and liver—resulting in progressive organ failure and life-threatening complications. Etentamig targets B-cell maturation antigen (BCMA) on cancer cells and CD3 on T cells, harnessing your immune system to destroy the tumor. In a phase 1b study, etentamig achieved a 64% ORR in BCMA-exposed R/R MM, with 67% MRD negativity and a median response duration of 13 months. Only low-grade cytokine release syndrome (CRS) was observed, and the safety profile was favorable even without step-up dosing. (Abstract 7508) [10][11][12]
Real-World and Biomarker Studies
Colorectal Cancer (mCRC)
- A US-based retrospective study of 1,817 patients diagnosed between 2013 and 2024 with unresectable metastatic colorectal cancer (mCRC) who had evaluable longitudinal data captured in the first-line (1L)+ treatment setting, showed that, although guidelines recommend comprehensive biomarker testing for all patients with mCRC, evidence on its adoption, especially across lines of therapy (LoT), remains limited. The analysis demonstrated that biomarker testing rates were 77% at first-line, but fell to 47% at second-line (2L) and 30% at third-line (3L). Tissue samples were the primary source for testing, but repeat biopsies declined in later lines (2L and 3L). While testing rates improved over time, they remain suboptimal, highlighting the need for standardized protocols to optimize biomarker-driven therapy. (Abstract e15526).[13]
Ovarian Cancer
- In a retrospective study of 1,685 adult patients diagnosed with ovarian cancer between 2022 and 2025, early biomarker testing (BRCA, homologous recombination deficiency (HRD), and folate receptor α (FRα)) within 3 months of diagnosis, which is not a current clinical standard, was associated with a 32–38% reduction in risk of death and improved progression-free survival (PFS), underscoring the importance of prompt biomarker assessment. (Abstract e17574)
Discussion
The 2026 ASCO data reinforce the growing impact of next-generation ADCs and TCEs in addressing critical gaps in treatment for solid tumors and hematologic malignancies. c-Met–, SEZ6–, PSMA/STEAP1–, and FRα–targeted ADCs show promising efficacy, often in biomarker-selected populations or combination regimens. The integration of immune checkpoint inhibitors further augments these advances, as seen in SCLC and NSCLC trials. Real-world and retrospective biomarker studies emphasize the necessity of standardized, timely testing to fully realize the benefits of precision oncology. T-cell engagers, such as etentamig, are also advancing the therapeutic horizon in heavily pretreated hematologic malignancies.
Antibody-drug conjugates (ADCs) and T-cell engagers (TCEs) are rapidly reshaping the therapeutic landscape across oncology, offering hope in settings where conventional therapies have limited efficacy. Ongoing and future trials will clarify optimal sequencing, biomarker selection, and combination strategies, thereby further individualizing and improving cancer care.
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Note: Unless otherwise specified, agents discussed are investigational. Safety and efficacy continue to be evaluated in ongoing clinical trials.
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
A Study to Assess Adverse Events and Change in Disease Activity of Intravenous (IV) Telisotuzumab Adizutecan Compared to Standard of Care in Adult Participants With Locally Advanced or Metastatic EGFR-Mutated Non-Squamous Non-Small Cell Lung Cancer – ClinicalTrials.gov ID NCT07155187
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
A Study to Assess Adverse Events and Change in Disease Activity in Participants 12 Years of Age or Older With Locally Advanced or Metastatic Solid Tumors That Harbor MET Amplification Receiving Intravenously Infused Telisotuzumab Adizutecan – ClinicalTrials.gov ID NCT07196644
Study of Telisotuzumab Vedotin (ABBV-399) in Participants With Previously Treated c-Met+ Non-Small Cell Lung Cancer – ClinicalTrials.gov ID NCT03539536
A Study to Evaluate the Optimal Dose, Adverse Events, and Change in Disease Activity of Intravenous ABBV-706 in Combination With Atezolizumab Versus Standard of Care as First-Line Treatment in Adult Participants With Previously Untreated Extensive Stage Small Cell Lung Cancer (SEZanne) – ClinicalTrials.gov ID NCT07155174
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
A Study to Assess Adverse Events, and How Intravenously (IV) Infused ABBV-969 Moves Through the Bodies of Adult Participants With Metastatic Castration-Resistant Prostate Cancer – ClinicalTrials.gov ID NCT06318273
A Study of Mirvetuximab Soravtansine vs. Investigator’s Choice (IC) of Chemotherapy in Platinum-Resistant, Advanced High-Grade Epithelial Ovarian, Primary Peritoneal, or Fallopian Tube Cancers With High Folate Receptor-Alpha (FRα) Expression (MIRASOL) – ClinicalTrials.gov ID NCT04209855
Highlights of Prescribing Information
Osimertinib (Tagrisso®; AstraZeneca)[Prescribing Information]
Telisotuzumab Vedotin (Teliso-V; ABBV-399; Emrelis®; AbbVie) [Prescribing Information]
Mirvetuximab Soravtansine (IMGN-853; Elahere®; AbbVie) [Prescribing Information]
Reference
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Featured image courtesy of © 2022 – 2026 ASCO/Scott Morgan. Used with permission.
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