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With renewed focus and commitment in creating a platform for innovative scientific insights and transformative experiences, 13th World ADC in London, held March 13 – 16, 2023, is expected to present exciting clinical progress of antibody-drug conjugates as monotherapy and in combination therapies. In addition, expect updated presentations covering next-generation novel formats, and tools designed to optimizing both early and late-stage manufacturing processes.

Organized by Hanson Wade, World ADC London will clearly demonstrate that the development and utilization of ADC is rapidly changing.  This change, notable in the record breaking 211 new ADCs entering clinical trials in 2022, shows that antibody-drug conjugates are surpassing all imaginable and preceived imitations.

Today, there are total of 337 antibody-drug conjugates in the development pipeline.  Sixty-two percent (62%) of these ADC are in preclinical development. Nineteen percent (19%) of ADCs in development are phase 1, 12% in phase 2, 3% in phase 3 and 4% of all ADC are approved by the U.S. Food and Drug Administration and commercially available. [1]

In addition to traditional ‘real’ antibody-drug conjugates are more than 250 bioconjugates modalities, including, but including bioconjugates with non-cytotoxic payloads (oligonucleotides, chelators, polymers, oligosaccharides) and ‘novel format conjugates’ with alternative target-binding formats (scFv fragments, nanobodies, cyclic peptides).

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So, what can attendees expect?

This year, World ADC 2023 in London offers a one-stop shop for antibody-drug conjugate content, uniting all leading players in the field of under one roof, to discuss advances the development of ADCs. Without a doubt, this year World ADC in London is set to be the best version of the event yet, with a packed agenda offering valuable insights into the status of ADC discovery, development, manufacturing and testing, as well as workshops that showcases the development of novel format conjugates outside of the traditional antibody targeting proteins. And, there will be major highlights from the key antibody-drug conjugate developers including Daiichi Sankyo, Immunogen and Seagen, as well presentations discussing Pharmacokinetics in preclinical and clinical development and manufacturing.

In this overview, our editors review just a few exciting details.

Folate receptor alpha
On November 14, 2022, the FDA granted accelerated approval to mirvetuximab soravtansine-gynx (Elahere®; ImmunoGen), a folate receptor alpha (FRα) directed antibody and microtubule inhibitor conjugate, for adult patients with folate receptor alpha positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received one to three prior systemic treatment regimens.[2]

“With an indication for use regardless of prior treatment with bevacizumab (Avastin®; Genentech/Roche), we believe mirvetuximab soravtansine-gynx is positioned to become the new standard of care for patients with FRα-positive platinum-resistant ovarian cancer,” noted Mark Enyedy, ImmunoGen’s President and Chief Executive Officer. “The accelerated approval of mirvetuximab soravtansine-gynx is a testament to the decades of work dedicated to developing the next generation of ADCs,” he added.

The approval of mirvetuximab soravtansine-gynx is significant for patients with FRα-positive platinum-resistant ovarian cancer, which is generally characterized by limited treatment options and poor outcomes. The impressive anti-tumor activity, durability of response, and overall tolerability observed in the SORAYA study have demonstrated the benefit of this new therapeutic option.

Patients are selected for therapy based on the results from Roche’s VENTANA FOLR1 (FOLR1-2.1) RxDx assay, the first FDA-approved immunohistochemistry (IHC) companion diagnostic test to help identify patients with epithelial ovarian cancer who are eligible for treatment with mirvetuximab soravtansine-gynx.[3]

During World ADC, 2023, Olga Ab, Director, Product Team Lead at ImmunoGen will discuss the “Next Big Step: Perfecting ADC Design to Improve Clinical Outcome.”  In her presentation, Ab will present how scientists and researchers can learn from the mirvetuximab soravtansine-gynx clinical experience to design a next generation FR targeting ADC with improved activity against a broader patient population.

Sam Lawn, Senior Scientist & Group Lead, In Vivo Biology & PK at Zymeworks, will updated the meeting attendees about ZW191, a folate Receptor-⍺ Targeted Topoisomerase 1 Inhibitor ADC being developed by the company. ZW191, currently in pre-clinical development, integrates a highly effective FRa-targeting antibody with Zymework’s novel camptothecin-based TOPO1 inhibitor platform. Lawn will share preclinical studies have demonstrated that the novel agent favorable activity and tolerability profiles.  Lawn will also discuss the potential for a differentiated ADC to deepen and expand responses in patients with tumors expressing a range of FRa levels

‘HER2-low’ cancers
In addition, positive results from DESTINY-Breast04 involving patients with HER2-low metastatic breast cancer, demonstrated that trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo and AstraZeneca) resulted in significantly longer progression-free and overall survival than the physician’s choice of chemotherapy. [3]

This is good news for patients diagnosed with breast cancers without human epidermal growth factor receptor 2 (HER2) amplification, overexpression, or both. The results of this study show that a large proportion – in approximately 60% of patients – these breast cancers express low levels of HER2 that may be targetable. However, currently available HER2-directed therapies have been ineffective in the treatment of patients with these ‘HER2-low’ cancers.[3]. Prior the approval of trastuzumab deruxtecan, HER2-low patients received endocrine therapy or chemotherapy.

During World ADC, 2023, London, Gerold Meinhardt, Vice President, Global Team Leader, Asset & Portfolio Management Daiichi Sankyo, will discuss lessons learnt, optimizing the success and the Case History of the ADC ‘Poster Child’ trastuzumab deruxtecan.  In his presentation Meinhardt will exploring the significant opportunities of trastuzumab deruxtecan following its unprecedented success in HER-2 negative breast cancer; discuss the unique qualities of trastuzumab deruxtecan that have contributed to it success, including the low potency payload, the cleavability of the linker and the bystander effect, and outlining which of these qualities specifically can be taken forward in future ADCs. Meinhardt will also outline what the success of trastuzumab deruxtecan means for the future of ADC design and adapting approved ADCs for novel indications.

‘Her2-positive’ cancers
Antibody-drug conjugates have shown impressive results in the treatment of metastatic breast cancer (mBC). Treatment options in the later-line HER2- positive setting include ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche). In addition, Ujvira® a trastuzumab emtansine biosimilar (previously known as ZRC- 3256) developed by Zydus Cadila, is approved in India [4]

Results from a phase 3, randomized, open-label, active-controlled study conducted at 31 sites across India and a total of 168 enrolled patients randomized to receive either the bio similar or the reference drug, demonstrated biosimilarity between the two ADCs in terms of efficacy, safety, pharmacokinetics, and immunogenicity. Based on this outcome, it is believed that the trastuzumab emtansine biosimilar could potentially prove to be a cost-effective treatment alternative for HER2-positive metastatic breast cancer patients.

Next-generations HER2-positive ADC therapies may also including disitamab vedotin (爱地希® | Aidixi®; RemeGen/Seagen). Previously known as RC48. the drug is conditionally approved in China for locally advanced metastatic HER2- positive gastric cancer.

Disitamab vedotin combines the drug-linker technology originally developed by Seagen with RemeGen’s novel HER2 antibody exhibiting higher affinity and an increased internalization rate as compared to trastuzumab in preclinical models.[5] As monotherapy, disitamab vedotin demonstrated antitumor activity in clinical trials in several solid tumor types, including urothelial, gastric and breast cancer, as well as across a spectrum of HER2 expression levels. In addition, promising combination activity was demonstrated with a PD-1 inhibitor in urothelial cancer. It is believed that vedotin-based immunogenic cell death (ICD) may differentiate this class of ADC’s when combined with checkpoint inhibitors.

Trastuzumab duocarmazine
This year may also turn out to be record-breaking, with high hopes for the approval of Byondis‘ [vic-] trastuzumab duocarmazine (SYD985) in patients with HER2-positive unresectable locally advanced or metastatic breast cancer (MBC). The ADC comprises of trastuzumab covalently bound to a linker drug containing duocarmycin, a payload/drug which was superior versus chemotherapy in pretreated HER2-positive metastatic breast cancer in the phase 3 TULIP® multi-center, open-label, randomized clinical trial. The company has been given a Prescription Drug User Fee Act (PDUFA) action date of May 12, 2023.

Triple negative breast cancer
Sacituzumab govitecan-hziy (Trodelvy®; Gilead), a humanized Trop-2 IgG1 kappa antibody coupled to the topoisomerase inhibitor SN-38 through a proprietary hydrolysable linker. Sacituzumab govitecan-hziy, a first-in-class ADC which was granted accelerated approval in April 2021 is expected to transform the treatment of metastatic triple negative breast cancer (mTNBC).  In addition to TNBC, sacituzumab govitecan-hziy is also in development in non-small cell lung cancer.

Due to its high expression on the surface of malignant cells relative to normal cells and its internalization upon ligand binding, Trop2 is an attractive therapeutic target for antibody-drug conjugates ADCs

Because effective treatment options are extremely limited for mTNBC, the strong data in this setting suggest that sacituzumab govitecan-hziy will, most likely, be quickly integrated into standard of care and, as a result, transform the treatment of this disease.

However, only 12 – 15% of patients diagnosed with breast cancer are ‘triple negative,’ and with up to 40% of TNBC patients being PDL1-positive new treatment options early in the treatment paradigm, including atezolizumab (Tecentriq®; Genentech/Roche), a programmed cell death ligand 1 (PD-L1)-blocking checkpoint inhibitor approved for first-line triple negative breast cancer in March 2019, and pembrolizumab (Keytruda®; Merck & Co) approved for TNBC in November 2020, the potential market share of sacituzumab govitecan-hziy for the labelled indication may be limited.

In addition, potentially directly competing with sacituzumab govitecan-hziy following regulatory approval are investigational agents currently in clinical development, including datopotamab deruxtecan (Dato-DXd; Daiichi Sankyo), which also targets Trop2 and has shown impressive clinical data in TNBC with a 43% response rate according to early-stage data from the TROPION-Breast02 study, and ladiratuzumab vedotin (SGN-LIV1A; Seagen), an antibody-drug conjugate targeting the zinc transporter transmembrane protein LIV1A which harbors protease activity and which has shown encouraging data in an ongoing phase I study in metastatic breast cancer including triple negative breast cancer.

Unrelated to TNBC, the MORPHEUS trial is investigating sacituzumab govitecan-hziy, in combination with atezolizumab, for the treatment of patients diagnosed with metastatic urothelial cancer (mUC) and metastatic non-small cell lung cancer (mNSCLC).

Pharmacokinetics in preclinical and clinical development
In the preclinical and clinical development of novel drugs, one of the key elements to study is pharmacokinetics.  Pharmacokinetics is generally defined  as the study of the time course of drug absorption, distribution, metabolism, and excretion.

For complex drug molecules, especially for ADC’s, this can be very challenging as many different forms of the drug can exist: specifically the Drug-Antibody-Ratio (DAR) can change in time; the payload can be released in circulation; the ADC can bind to soluble antigen; metabolism in the Cell Danger Response (CDR) can occur, all of which can impact the efficacy of the ADC. This, in turn, results in a challenge for the bioanalytical scientist as they need to develop robust assays for these different forms.

On Wednesday, March 15, Benno Ingelse, Ph.D., Director Bioanalysis & Protein Interaction will present “Bioanalytical challenges in quantifying “Total” and “Free” Antibody-Drug-Conjugates.”*

In his presentation, Ingelse will discuss some of these challenges and zoom in on the preclinical and clinical bioanalytical assays that Byondis has developed in support of Byondis’ BYON3521, an investigational ADC comprised of the humanized IgG1 monoclonal antibody SYD2884, targeting c-MET, and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA or SYD980). BYON3521 employs site-specific conjugation to an engineered cysteine residue located on heavy chain position 41 of the antibody.

Based on cynomolgus monkey data, generated with the company’s bioanalytical tools, Ingelse will present human PK predictions. A First-in-Human dose escalation study with BYON3521 is currently ongoing to determine the maximum tolerated dose and recommended dose for expansion (NCT05323045). The study is enrolling patients in leading oncology centers in Belgium, Italy, the Netherlands and the United Kingdom. The quality of the human PK predictions and thus the quality of the bioanalytical tools, will be illustrated by also presenting early stage clinical PK data from this study.

Novel formats conjugates
This years, novel formats conjugates continue to break new ground in the targeted delivery of cytotoxic payloads. Compared to traditional ADCs, these ‘novel formats conjugates’ are expected to further improve the therapeutic index. The novel format conjugates are expected to make further inroads in the treatment of solid tumors as a therapeutic alternative to traditional antibody delivery of cytotoxin payloads.

Among the variety of technologies being developed are Bicycles, fully synthetic short peptides constrained to form two loops which stabilize their structural geometry. This constraint is designed to confer high affinity and selectivity, and the relatively large surface area presented by the molecule allows targets to be engaged that have historically been intractable to non-biological approaches.

The technology, which arose from research by Sir. Greg Winter, CBE FRS FMedSci, winner of the Nobel Prize in Chemistry in 2018 for his pioneering work in phage display, has led to major therapeutic advances in antibody based therapeutics; and bicyclic peptide (Bicycle) drug discovery and development.

Among the ‘novel format conjugates’ are investigational agents being developed by Bicycle Therapeutics clinical candidates, including BT8009. This investigationalsynthetic Bicycle Toxin Conjugate targets Nectin-4, a cell adhesion molecule from the Nectin and Nectin-like family, which has been shown to be over-expressed in tumor cells and is believed to play a role in tumor cell growth and proliferation. High in normal embryonic and fetal tissue, Nectin-4, which is a validated target for cytotoxin delivery, declines in adulthood, showing a limited distribution in healthy tissues. BT8009 is composed of a Nectin-4 targeting Bicycle®, a valine-citrulline, or val-cit, cleavable linker, and an MMAE cytotoxin payload.

In preclinical models, BT8009 has demonstrated promising target-dependent activity, including both cell- and patient-derived xenografts resistant to current standard of care treatments. In addition, in preclinical head-to-head comparisons with enfortumab vedotin (Padcev®; Astellas Pharma and Seagen), an ADC targeting Nectin-4 which received US FDA approval in December 2019 for use in advanced urothelial cancer, BT8009 appeared to demonstrate superior anti-tumor activity, including complete regressions in both very large and small tumor models.  Preclinical toxicity studies with BT8009 further showed only a subset of the toxicities typically associated with the MMAE cytotoxin payload, avoiding liver, GI and renal toxicity.

Another Bicycle Toxin Conjugate, BT5528, is designed to targets EphA2, a member of the Ephrin superfamily of receptor tyrosine kinases, which regulates cell migration, adhesion, proliferation and differentiation during development.  This investigational ‘novel format conjugate’ comprises composed B EphA2 targeting Bicycle®, a valine-citrulline (val-cit) cleavable linker and a monomethyl auristatin E (MMAE) cytotoxin payload.  The investigational drug is being evaluated in a phase I/II clinical trial as a potential monotherapy and in combination with nivolumab (Opdivo®; Bristol-Myers Squibb).

During World ADC 2023, London, Mark Frigerio, Vice President, Chemistry at Bicycle Therapeutics will present the latest data discussing the Bicyclic Peptide (Bicycle) Toxin Conjugates and what kind of advancements these novel format conjugate may offer over traditional ADCs. In his presentation Frigerio will discuss:

  • Bicycles are a unique therapeutic modality combining the pharmacology usually associated with a biologic with the manufacturing and PK properties of a small molecule
  • Bicycles are fully synthetic constrained peptides that bind with high affinity and selectivity that have a short systemic exposure with tumour retention
  • Bicycles can be used to deliver key pharmacological activity for solid tumours using cytotoxic payloads and are currently being explored in the clinic as Bicycle toxin conjugates® (BTCs)

Antibody Oligonucleotide Conjugates – Process and Analytical Challenges
Oligonucleotide therapies, with indications ranging from age-related macular degeneration, homozygous familial hypercholesterolemia to spinal muscular atrophy in infants, have been in clinical development for the past 30 years. To deliver GMP quality clinical supplies, process and analytical development of AOCs has posed new challenges.

Process chemistry operations must ensure specific distribution of oligonucleotide to antibody is achieved, process operations must deliver pure, formulated drug substance at kilogram scale, and robust analytical testing is essential to define key quality attributes and determine product stability.

During World ADC in London, a team from Merck Life Science Services, an industry leader supplying early and late-phase AOC clinical supplies, will present specific examples of process and analytical development challenges and highlight the company’s robust development offerings and expertise.

Manufacturing & Supply Chain
To mitigate the challenges associated with ADC development and manufacturing, between 70-80% of the drug developers outsource their operations to contract development and manufacturing organizations (CDMO), who have the required expertise and experience to leverage their capabilities and yield cost savings opportunities. But how can  a successful working relation be developed?

During World ADC 2023, London, Robert Herbst, Vice President, Technical Operations at ImmunoGen will discuss the successful integration with CDMOs to successfully validate all components of antibody-drug conjugates and discuss and share his experiences regarding the utilization of a fully outsourced model to develop/manufacture early-stage ADCs as well as the continued optimization of integration between client and external vendor will be discussed.(Tuesday, March 14, 9:00 am)

On Tuesday, March 14, During World ADC 2023, London, Lisa McDermott, Director of Process and Analytical Development, Merck Life Sciences, will chair the program stream Minimising ADC Manufacturing Timelines.

During this program, Steffen Woell, Principal Scientist at Merk KGaA, Germany, discusses, outline and provide insights in a new state of the art pilot manufacturing unit for ADCs:

  • How internal capabilities can reduce interfaces and transfer times in CMC timelines, and thus help to shorten development timelines
  • How the development of high potency APIs, located between the lab scale and GMP manufacturing, poses special challenges in terms of safety, quality and representativeness
  • How the build-up of an ADC process development, and preclinical manufacturing unit for liquid and lyophilized ADC DP

Applications of PAT for Bioconjugation Processes
During the Plenary Speaking Engagement, Day 1 Tuesday 14th March at 16:45, Jake Spies, Senior Scientist Group Lead Process & Analytical Development, Merck Life Science and Haowei Song, Principal Scientist in Novel Modalities R&D, Merck Life Science covering

  • Pros and cons of in(on)line testing for bioconjugation process
  • PATs at different steps of bioconjugation process
  • Case studies for real-time monitoring the reduction and conjugation process by online HPLC

Ross Bemowski, Associate Director, API R&D, Merck Life Sciences, will discuss innovative chitooligosaccharide-based solubility enhancer for linker/payloads, leading to improved efficacy and ‘new life’ for challenging payloads (Poster Session, Day 1, 5:45 PM).  In the presentation, Bemowski will introduce, discuss and present the company’s:

  • Chetosensar® technology, a new chitooligosaccharide-based solubility enhancer that can be used with a wide range of linker-payload chemistries and conjugation methods.
  • Invitro studies demonstrating increased efficacy and previously unattainable high DAR species
  • How Chetosensar® technology works with our CDMO services and ADCore™ intermediates to deliver rapid access to new linker-payloads

Early ADC development
Abderrahman Laadem, Vice President, Head, Early Oncology Development at Daiichi Sankyo reviews Daiichi Sankyo’s Early ADC development pipeline and clinical program, Including I-DXd (DS-7300) and DS- 6000.

  • Ifinatamab deruxtecan (I-DXd; also known as DS-7300) is a novel enzymatically cleavable, B7-H3–directed ADC that leverages the clinically validated deruxtecan (DXd) technology, currently in Phase 1/2 trials.  B7-H3 is a type I transmembrane protein belonging to the B7 family which includes immune checkpoint molecules CTLA-4 ligands and PD-L1. B7-H3 is highly expressed in various types of solid tumors with low expression in normal (healthy) tissues. Several studies have reported that B7-H3 over-expression is associated with poor prognosis in several types of cancers.  A clinical trial which includes the investigational drug in the treatment of Extensive-stage Small-cell Lung Cancer, is ongoing.
  • DS-6000 is a cadherin 6 (CDH6) directed DXd antibody drug conjugate currently in Phase 1 trial. The investigational drug is designed using Daiichi Sankyo’s proprietary DXd ADC technology and comprises a humanized anti-CDH6 IgG1 antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers. The drug’s target, the CDH6 protein is significantly overexpressed in ovarian cancer and renal cell carcinoma and has been identified as a promising therapeutic target. Overexpression of CDH6 is associated with tumor growth and proliferation and is correlated with poor prognosis in patients with renal cell carcinoma. Today, no CDH6 directed cancer therapies are currently approved for treatment of any cancer. Initial results from the first-in-human phase 1 study of DS-6000 suggest early clinical activity in patients with advanced ovarian cancer or renal cell carcinoma with disease progression following standard of care treatment. The data were presented today in an oral session (Abstract #3002) at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO) [5][6][7]

ifinatamab deruxtecan and DS-6000 are being developed through a strategic early-stage research collaboration with Sarah Cannon Research Institute.

Meeting the challenge in early ADC Development
The early development of antibody-drug conjugates can be challenging. Addressing the challenge, Nicolas Camper, Senior Director, Bioconjugation Chemistry, Abzena will present how to leveraging linker design and drug developability assessment to develop successful ADCs.

Camper will discuss how linker chemistry represent more than a bridge between the antibody and payload and plays a role in modulating ADCs biological activity. He will further discuss how to identifying the best combination of antibody, linker and payload and how to ‘meet the challenge’ by applying stage-specific evaluation criteria to de-risk ADC candidate selection with the best chance of clinical success, and, finally, Camper will discuss cases studies on how to construct and evaluate appropriate ADC candidate matrices varying payloads and linker elements for lead candidate selection.

Meeting the challenges of life cycle management in ADC Manufacturing
Addressing the complexity in the development and manufacturing of ADCs, Charlotte Sornay, MSAT Associate Principal Scientist in Bioconjugates at Lonza in Visp, Switzerland, will present an overview of the  is “MSAT: Your Lifecycle Partner for Clinical to Commercial Manufacturing.” In her presentation, Sornay will outline the next challenges in the manufacture of ADCs and bioconjugates, introducing the role of MSAT Bioconjugates for the support of clinical re-supplies and commercial manufacturing and defining MSAT’s specific activities: process changes and improvements, batch scale optimization, process validation and IND/BLA filing.

Other noteworthy presentations
During World ADC, London, do miss the presentations from:

  • William Grossman, Vice President, Oncology Clinical Development, Therapeutic Area Head at Gilead Sciences.  In his presentation “The Race to the Next Approval: Outlining the Exciting Clinical Progress in the ADC Field,” Grossman will discuss exciting new clinical data in the ADC field, outlining the best path of progression to approval and providing a late-stage clinical development overview of the most exciting clinical therapeutics
  • Yutaka Matsuda, ADC Project Manager at Aji Bio-Pharma Services will discuss the company’s propriatary AJICAP® Conjugation. In the presentation Matsuda examines how site-specific technologies are being employed in many of the next-generation ADCs due to the enhancement of clinically relevant biological properties observed in various preclinical studies.  He also shares updated information about the company’s AJICAP® Linker, a novel hydrophilic linker technology, enables the versatile synthesis of homogenous DAR = 1, 2, 4, 8, and higher
  • Gordon Rigg, Principal Consultant, Apex Biologics Consulting will address the developability assessment for ADCs and novel formats.  In his presentation, Rigg will Outline how to integrate developability assessment at the interface between research and CMC; how to take a novel format conjugate or ADC from research into technical development; outlining developability assessment study design for protein and conjugate selection, and discuss analytical approaches in developability assessment.

In this overview, we’ve only addressed some of the highlights of what attendees can expect during the 13th World ADC, in London, Europe’s Definitive Antibody-Drug Conjugate meeting!

_

Note: * During the ‘Process & Analytical Development Stream’ on Wednesday 15 March, 2023

Clinical trials
Trastuzumab Deruxtecan (DS-8201a) Versus Investigator’s Choice for HER2-low Breast Cancer That Has Spread or Cannot be Surgically Removed [DESTINY-Breast04] – NCT03734029
Disitamab Vedotin Combined With PD-1 and Neoadjuvant Chemotherapy for Locally Advanced Gastric Cancer(RC48-C018)- NCT05113459
A Clinical Study of Disitamab Vedotin for Injection Combined With Penpulimab Injection in Neoadjuvant Therapy for Patients With HER2-expressing Cisplatin-intolerant cT2-T4aNxM0 Bladder Urothelial Carcinoma – NCT05488353
Disitamab Vedotin Combined With Tislelizumab for Her2 Overexpressing High-Risk Non-Muscle-Invasive Urothelial Bladder Carcinoma Which is Not Completely Resectable – NCT05495724
SYD985 vs. Physician’s Choice in Participants With HER2-positive Locally Advanced or Metastatic Breast Cancer (TULIP) – NCT03262935
A First-in-human Dose-escalation and Expansion Study With the Antibody-drug Conjugate BYON3521 – NCT05323045
Datopotamab Deruxtecan (Dato-DXd) in Combination With Pembrolizumab With or Without Platinum Chemotherapy in Subjects With Advanced or Metastatic Non-Small Cell Lung Cancer (TROPION-Lung02) – NCT04526691
A Study of Dato-DXd Versus Investigator’s Choice Chemotherapy in Patients With Locally Recurrent Inoperable or Metastatic Triple-negative Breast Cancer, Who Are Not Candidates for PD-1/PD-L1 Inhibitor Therapy (TROPION-Breast02) – NCT05374512
Safety and Efficacy of SGN-LIV1A Plus Pembrolizumab for Patients With Locally-Advanced or Metastatic Triple-Negative Breast Cancer – NCT03310957
A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer (Morpheus-TNBC) – NCT03424005
Ifinatamab Deruxtecan (I-DXd) in Subjects With Pretreated Extensive-Stage Small Cell Lung Cancer (ES-SCLC) – NCT05280470

Highlights of prescribing information
Mirvetuximab soravtansine-gynx (Elahere®; ImmunoGen)[Prescription information]
Atezolizumab (Tecentriq®; Genentech/Roche) [Prescription information]
Enfortumab vedotin (Padcev®; Astellas Pharma and Seagen[Prescription information]
Bevacizumab (Avastin®; Genentech/Roche) [Prescription information]
Ado-trastuzumab emtansine (Kadcyla®; Genentech/Roche) [Prescription information]
Sacituzumab govitecan-hziy (Trodelvy®; Gilead)[Prescription information]
Trastuzumab deruxtecan (Enhertu®; Daiichi Sankyo and AstraZeneca)[Prescription information]

References
[1] Data on file – ADC Review | J. Antibody-drug Conjugates
[2] FDA Approves Mirvetuximab Soravtansine-gynx for FRα+ Platinum-resistant Ovarian Cancer; ADC Review | Editorial Team – November 14, 2022 [Article]
[3] Modi S, Jacot W, Yamashita T, Sohn J, Vidal M, Tokunaga E, Tsurutani J, Ueno NT, Prat A, Chae YS, Lee KS, Niikura N, Park YH, Xu B, Wang X, Gil-Gil M, Li W, Pierga JY, Im SA, Moore HCF, Rugo HS, Yerushalmi R, Zagouri F, Gombos A, Kim SB, Liu Q, Luo T, Saura C, Schmid P, Sun T, Gambhire D, Yung L, Wang Y, Singh J, Vitazka P, Meinhardt G, Harbeck N, Cameron DA; DESTINY-Breast04 Trial Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer. N Engl J Med. 2022 Jul 7;387(1):9-20. doi: 10.1056/NEJMoa2203690. Epub 2022 Jun 5. PMID: 35665782.
[4] Chiradoni Thungappa S, Maksud T, Raut N, Nagarkar R, Batra U, Kumar S, Parmar D; Study Investigator Group. Comparison of the Efficacy, Safety, Pharmacokinetic and Immunogenicity of UJVIRA (ZRC-3256, Trastuzumab Emtansine) With the Kadcyla (Trastuzumab Emtansine) in the Treatment of HER2-Positive Metastatic Breast Cancer: A Randomized, Open-Label, Multicenter Study in India. Clin Breast Cancer. 2022 Jun;22(4):300-307. doi: 10.1016/j.clbc.2021.11.006. Epub 2021 Nov 27. PMID: 34955432.
[5] Yao X, Jiang J, Wang X, Huang C, Li D, Xie K, Xu Q, Li H, Li Z, Lou L, Fang J. A novel humanized anti-HER2 antibody conjugated with MMAE exerts potent anti-tumor activity. Breast Cancer Res Treat. 2015 Aug;153(1):123-33. doi: 10.1007/s10549-015-3503-3. Epub 2015 Aug 8. PMID: 26253944.
[6] Bartolomé RA, Robles J, Martin-Regalado Á, Pintado-Berninches L, Burdiel M, Jaén M, Aizpurúa C, Imbaud JI, Casal JI. CDH6-activated αIIbβ3 crosstalks with α2β1 to trigger cellular adhesion and invasion in metastatic ovarian and renal cancers. Mol Oncol. 2021 Jul;15(7):1849-1865. doi: 10.1002/1878-0261.12947. Epub 2021 May 2. PMID: 33715292; PMCID: PMC8253092.
[7] Bialucha CU, Collins SD, Li X, Saxena P, Zhang X, Dürr C, Lafont B, Prieur P, Shim Y, Mosher R, ey al. Discovery and Optimization of HKT288, a Cadherin-6-Targeting ADC for the Treatment of Ovarian and Renal Cancers. Cancer Discov. 2017 Sep;7(9):1030-1045. doi: 10.1158/2159-8290.CD-16-1414. Epub 2017 May 19. PMID: 28526733.
[8] Tenold M, Ravi P, Kumar M, Bowman A, Hammers H, Choueiri TK, et al. Current Approaches to the Treatment of Advanced or Metastatic Renal Cell Carcinoma. DOI: 10.1200/EDBK_279881 American Society of Clinical Oncology Educational Book 40 (April 2, 2020) 187-196.

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