The antibody-drug conjugate (ADC) field continues to evolve at an unprecedented pace. During the past week alone, regulatory decisions, pivotal clinical trial expansions, and strategic platform investments underscored two major trends that are reshaping oncology drug development: the continued movement of ADCs into earlier lines of therapy and the rapid emergence of B7-H3 (CD276) as one of the most competitive targets in solid tumors.
While established targets such as HER2 and TROP2 continue to expand into frontline treatment settings, a growing number of companies are investing heavily in B7-H3-directed ADCs, bispecific ADCs, and dual-payload technologies designed to improve efficacy while overcoming resistance mechanisms.
Frontline Treatment Paradigms Continue to Shift
Two positive opinions from the Committee for Medicinal Products for Human Use (CHMP) illustrate how ADCs are increasingly challenging long-established standards of care.
HER2-positive metastatic breast cancer
The CHMP recommended approval of trastuzumab deruxtecan (Enhertu®) combined with pertuzumab as first-line treatment for HER2-positive metastatic breast cancer after results demonstrated a 44% reduction in the risk of disease progression or death compared with the long-standing regimen of trastuzumab, pertuzumab and chemotherapy (THP).
The recommendation reflects a broader transition in oncology, where ADCs are no longer reserved for patients with refractory disease but are increasingly becoming components of initial treatment strategies.
Triple-negative breast cancer
Similarly, the CHMP supported sacituzumab govitecan (Trodelvy®) in combination with pembrolizumab for patients with PD-L1-positive first-line metastatic triple-negative breast cancer (mTNBC). Clinical data demonstrated approximately a 35% reduction in the risk of progression or death, further expanding the role of TROP2-directed therapy in earlier treatment settings.
Together, these regulatory milestones reinforce the growing clinical confidence in ADC-based combinations as frontline therapy across multiple tumor types.
B7-H3: A Fast-Growing Target
Among recent developments, the most notable trend was the continued acceleration of B7-H3-directed therapeutics. B7-H3 (CD276), a member of the B7 family of immune regulatory proteins, is highly expressed across numerous solid malignancies—including prostate, lung, breast, head and neck, ovarian, neuroblastoma, glioblastoma, and other tumors—while exhibiting relatively limited expression in normal tissues. These characteristics have made B7-H3 an increasingly attractive target for antibody-drug conjugates.
As previously reviewed in ADC Review | Journal of Antibody-drug Conjugates, numerous clinical programs are now competing within the rapidly expanding B7-H3 landscape, utilizing diverse linker technologies, payloads, and antibody engineering approaches.[1][2]
The Commercial Race Intensifies
Several recent announcements further illustrate how quickly the field is moving toward commercialization. Duality Biologics and BioNTech announced that DB-1311 (BNT324) has been proposed for Breakthrough Therapy Designation in China for metastatic castration-resistant prostate cancer following androgen receptor pathway inhibitors and taxane therapy. Meanwhile, MediLink Therapeutics reported that China’s National Medical Products Administration (NMPA) accepted the New Drug Application (NDA) for YL201, potentially positioning it as one of the first commercially available B7-H3 ADCs for nasopharyngeal carcinoma. Both developments suggest that China continues to play a leading role in the clinical development of next-generation ADCs.
Expanding Clinical Pipeline
Clinical development also advanced across multiple B7-H3 programs. MacroGenics announced that its B7-H3 ADC, MGC026, met the enrollment threshold to advance to Stage 2 of its Phase 1 study in head and neck squamous cell carcinoma (HNSCC), adding further momentum to an increasingly crowded competitive landscape. Beyond conventional ADCs, several developers are pursuing differentiated strategies:
- Novel payload chemistries;
- Optimized linker technologies;
- Bispecific antibody-drug conjugates;
- Dual-payload ADCs designed to address tumor heterogeneity;
- Combination strategies incorporating immune checkpoint inhibitors or bispecific antibodies.
These approaches reflect broader efforts to improve therapeutic index while delaying or overcoming acquired resistance.
Platform Innovation Becomes a Key Differentiator
The week’s developments also highlighted how ADC innovation increasingly extends beyond target selection.
Bispecific ADCs
Sichuan Baili Pharmaceutical expanded pivotal Phase 3 evaluation of Iza-bren, an EGFR×HER3 bispecific ADC, across both breast and biliary cancers, illustrating growing confidence in bispecific targeting strategies.
Bispecific ADCs seek to improve tumor selectivity by recognizing two independent antigens, potentially increasing internalization and reducing off-target toxicity.
Dual-Payload ADCs
Qurient reported encouraging preclinical results for QP101, a dual-payload HER2-targeting ADC that demonstrated superior activity compared with trastuzumab deruxtecan in experimental models.
Although these findings remain preclinical, dual-payload technology represents an important area of investigation aimed at addressing tumor heterogeneity and resistance mechanisms. Clinical validation, however, remains essential before these approaches can be considered therapeutic advances.
Beyond B7-H3
Several additional programs demonstrated continued diversification of ADC development.
- Bio-Thera initiated Phase 1 evaluation of BAT8013, targeting CD25-positive regulatory T cells in solid tumors;
- Multitude Therapeutics advanced AMT-116, targeting CD44v9, into global Phase 2/3 development for EGFR wild-type non-small cell lung cancer.
- AstraZeneca also expanded investigation of datopotamab deruxtecan (Dato-DXd) combined with the PD-1/TIGIT bispecific antibody rilvegostomig into adjuvant treatment of muscle-invasive urothelial carcinoma through the Phase 3 TU-04 study, illustrating continued exploration of ADC–immunotherapy combinations in curative-intent settings.
Meanwhile, Telix Pharmaceuticals reported encouraging progress from the ProstACT SELECT study, which supports PSMA-PET imaging for patient selection in the ongoing global Phase 3 development of TLX591-Tx.
Commercial Strategy + Clinical Development
Beyond clinical progress, several commercial developments reflect broader strategic shifts within the ADC industry. Samsung Bioepis acquired exclusive rights to SBE303, representing another step beyond its traditional biosimilar portfolio toward innovative oncology therapeutics through its collaboration with IntoCell. Merck & Co (MSD) and GUARD initiated the Phase 2 RINGQUEST study evaluating sacituzumab tirumotecan in rare genitourinary tumors, extending TROP2-directed therapy into additional malignancies.
Conversely, reimbursement delays for the combination of enfortumab vedotin (Padcev®) and pembrolizumab in South Korea highlight an increasingly important challenge for high-cost combination regimens developed through collaborations among multiple pharmaceutical companies. As ADC combinations become more common, pricing, reimbursement, and health technology assessment are likely to become increasingly important determinants of commercial success.
Strong Biological Rationale
The rapid expansion of clinical programs targeting B7-H3 is supported by a growing body of translational research. Among recent studies, Mao and colleagues described the development of a homogeneous MMAE-based B7-H3 ADC utilizing a humanized monoclonal antibody and a divinylsulfonamide-mediated disulfide re-bridging conjugation strategy. The resulting construct demonstrated selective cytotoxicity against B7-H3-expressing glioblastoma models, tumor-specific accumulation in vivo, and dose-dependent antitumor activity in xenograft studies. [3] Although still preclinical, these findings further support B7-H3 as an attractive target for ADC development, particularly given its broad expression across solid tumors and relatively restricted expression in normal tissues.
Competition Clinical Candidates
The competitive landscape continues to broaden rapidly. Among the more advanced investigational agents are:
- Ifinatamab deruxtecan (I-DXd), currently under investigation in small-cell lung cancer and multiple solid tumors;
- Vobramitamab duocarmazine (MGC018), utilizing a duocarmycin payload in prostate cancer, neuroblastoma, and advanced solid tumors;
- SYS6043, an emerging B7-H3 ADC showing encouraging early clinical activity;
- GSK5764227 (also known as HS-20093), another next-generation B7-H3-targeting ADC currently undergoing early clinical evaluation.
Together, these programs illustrate the diversity of engineering approaches now being explored within the B7-H3 space.
What’s next
These developments reinforce several themes that are increasingly defining the ADC field.
- First, ADCs continue to be used earlier in the therapy sequence, supported by robust randomized clinical evidence.
- Second, B7-H3 has emerged as one of the most active areas of innovation in oncology drug development, with multiple clinical-stage programs pursuing differentiated antibodies, linker technologies, and payloads.
- Finally, platform innovation—including bispecific antibodies, dual-payload constructs, optimized conjugation chemistries, and biomarker-guided patient selection—is becoming as important as target selection itself.
Whether these technological advances ultimately translate into improved patient outcomes will depend on carefully conducted clinical trials. Nevertheless, the breadth of current investment suggests that the next several years may significantly reshape the competitive landscape for antibody-drug conjugates.
References
[1] Hofland P. B7-H3 (CD276) Antibody-Drug Conjugates: Emerging Therapeutic Opportunities in Solid Tumors. ADC Review | Journal of Antibody-drug Conjugates. Online.
[2] Hofland P. Rapid Advances in the Development of Novel ADCs Targeting B7-H3 and TROP2. ADC Review | Journal of Antibody-drug Conjugates. Online. Last accessed on August 14, 2026
[3] Mao Y, Wei D, Fu F, et al. Development of a MMAE-based antibody-drug conjugate targeting B7-H3 for glioblastoma. Eur J Med Chem. 2023;257:115489. doi:10.1016/j.ejmech.2023.115489. PMID:37235999.
Featured image © 2026 CH/JCO Used with permission.
