At ESMO 2024, the oncology field is witnessing the emergence of several new therapeutic classes, with numerous companies unveiling data from cutting-edge abstracts. We all are well aware about the novel immunotherapies, next-generation bispecific antibodies & ADCs, along with innovative immune checkpoint inhibitors. Now various pharma companies, including Pfizer, Bicycle Therapeutics, 23andMe, Sanofi, Biotheus, Amgen, Regeneron, Innovent Biologics, and others are testing some new classes. Brief highlights are mentioned below:

• The emergence of a never heard of a new class, Bicycle Therapeutics’ Bicycle Toxin Conjugates (BTC), BT8009 in PADCEV naive metastatic urothelial carcinoma. The company is also coming up with Nectin-4/CD137 Bicycle Tumor-Targeted Immune Cell Agonist (Bicycle TICA), BT7480 in solid tumors.

• EGFR inhibitors, FOLFOX/FOLFIRI, and anti-angiogenesis therapies are the gold standard of care in metastatic colorectal cancer, with Keytruda, Opdivo, and Jemperli being the PD-1 inhibitors approved, we look forward to the innovent's PD-1/1L-2 bispecific antibody fusion protein’s data readout

• Is Pfizer’s first-in-class CDK4 inhibitor expected to compete or work along with the well-established CDK4/6 inhibitors in HR+/HER2- Breast Cancer?

• The renal cell carcinoma treatment space is mainly dominated by immune checkpoint inhibitors (ICIs) and VEGF inhibitors, whereas the upcoming ones include 23andMe’s first-in-class anti-CD200R1 antibody (23ME-00610), Biotheus/BioNTech’s bispecific antibody (PD-L1/VEGF) (PM8002/ BNT327), and others.

• Several novel targets are emerging in ovarian cancers: Immunocore’s PRAME × CD3 ImmTAC T cell engager (brenetafusp), EZH2/EZH1 inhibitor (tulmimetostat), and Dual CHK1/2 inhibitor (ACR-368) among others.

• Sanofi is presenting updated Phase II results of its CEACAM5 inhibitor in 1st line NSCLC after it failed in a separate trial in 2nd line NSCLC.

• Metastatic Prostate Cancer patients heavily rely on androgen-deprivation therapies. With the recent strong uptake of Novartis’ radioligand therapy, we look forward to the data of a new class, Epizyme’s EZH2 inhibitor and Amgen’s STEAP1 x CD3 XmAb 2+1 Immune Therapy in patients with mCRPC.

Unveiling the latest in new emerging therapeutic classes

• Abstract Number – 652P
• Abstract Type – Poster session
• Indication - Metastatic urothelial carcinoma
• Class and target – Nectin-4 targeted Bicycle Toxin Conjugate (BTC)

Title: Excitement around the new class of Bicycle Toxin Conjugate (BTC) in metastatic urothelial carcinoma? Insights from the BT8009 Phase I/II Duravelo-1 trial  

Executive Summary- : Bicycle Therapeutics’s novel Bicycle Toxin Conjugate (BTC), BT8009 positioning as a viable first-line monotherapy for PADCEV-naive patients with metastatic urothelial carcinoma.

Visit our detailed report on Metastatic Urothelial Carcinoma Market and get a glimpse of the market is growing in the upcoming years.

Main Content –  

BT8009, a Nectin-4 targeted BTC, developed by Bicycle Therapeutics, represents a novel class of anti-cancer agents that combine the high specificity of small peptides with potent cytotoxic payloads. The Duravelo-1 trial evaluating BT8009 as monotherapy in enfortumab vedotin-naive patients with metastatic urothelial carcinoma (mUC) offers significant insights into the emerging role of Bicycle Toxin Conjugates in oncology. Urothelial carcinoma is the most common form of bladder cancer, accounting for approximately 90% of cases, with approximately 86,000 incident cases in the US, in 2023, as per DelveInsight.

In the Nectin-4 targeting space, BT7480 faces competition from PADCEV (enfortumab vedotin), the first antibody-drug conjugate (ADC) approved in Nectin-4-expressing bladder cancer. PADCEV has been a key player for patients who had previously been treated with immune checkpoint inhibitors. However, BT8009 offers enhanced tumor specificity. Unlike PADCEV, BT8009’s structure enables it to bind more precisely to tumor cells expressing Nectin-4, while sparing healthy tissues. Its ability to deliver a cytotoxic payload directly to cancer cells makes it a promising candidate for improving efficacy while maintaining a favorable toxicity profile. In preclinical head-to-head comparison with an ADC targeting Nectin-4, the drug appeared to demonstrate superior anti-tumor activity, including complete regressions in both very large and small tumor models. 

The Duravelo-1 trial continues to generate interest, with forthcoming data expected at the ESMO 2024, to clarify the potential impact of this BTC as monotherapy in PADCEV-naive patients with metastatic urothelial carcinoma. ​If successful, it could play a significant role as a first-line therapy in mUC, especially for cisplatin-ineligible patients. With no clear treatment options in this space, BT8009 may fill a critical gap.

In addition to this Phase I/II Duravelo-1 trial, the company is also conducting a Phase II/III Duravelo-2 trial, evaluating BT8009 as a treatment for metastatic urothelial cancer. BT8009 could achieve early regulatory approvals as a novel treatment option.

• Abstract Number – 750P
• Abstract Type – Poster session
• Indication - Platinum resistant ovarian cancer
• Class and target – PRAME × CD3 ImmTAC Bispecific T-cell engager

Title:  Immunocore is gearing up to unveil data for its Bispecific T-cell engager, Brenetafusp, in patients with platinum-resistant ovarian cancer

Executive Summary: Brenetafusp represents an exciting and innovative approach to treating platinum-resistant ovarian cancer. While ImmTACs are still emerging technologies, successful results could pave the way for expanded development of PRAME-targeted therapies across various cancers.

Read more about our newly launched report on Ovarian Cancer Market 2034.

Main Content –  

Brenetafusp, an ImmTAC (Immune-mobilizing monoclonal T-cell receptors against cancer) developed by Immunocore, is a first-in-class bispecific T cell engager designed to target PRAME and CD3 on T cells. PRAME is an intracellular cancer testis antigen overexpressed in various cancers, including ovarian, melanoma, and lung cancers, making it an attractive target for cancer immunotherapy. Brenetafusp binds to PRAME-presenting cancer cells and recruits cytotoxic T cells by engaging CD3, thereby enhancing T-cell-mediated killing of cancer cells.

Ovarian cancer is observed to be the eighth most common cancer in women with nearly 19,700 incident cases in the US, in 2023, as per DelveInsight. Platinum-resistant ovarian cancer remains a tough landscape, and despite multiple attempts, no highly effective treatments have emerged. Current treatment options include chemotherapy (such as pegylated liposomal doxorubicin and topotecan), PARP inhibitors (e.g., rucaparib, olaparib), and angiogenesis inhibitors (such as bevacizumab). However, these therapies offer only modest improvements in progression-free survival (PFS) and are often associated with significant toxicity.

The field of immunotherapy, especially T-cell engagers like brenetafusp, is beginning to gain traction, offering a novel mechanism of action. Competitors in the immunotherapy space include checkpoint inhibitors (such as pembrolizumab) and the recently approved ADC, such as FR-alpha targeting ELAHERE.

Immunocore is set to present the Phase I clinical data of brenetafusp as monotherapy and chemotherapy combinations in heavily pre-treated platinum-resistant high grade serous ovarian cancer as a poster at ESMO 2024. As per the company, the next step is to further evaluate brenetafusp in combination with non-platinum chemotherapies in platinum-resistant disease and to test the combination with platinum chemotherapy and with bevacizumab in platinum sensitive disease.

While the current trial is focused on PROC, PRAME is also overexpressed in other cancer types, such as melanoma, lung, and breast cancers. Success in ovarian cancer could open the door for multi-indication applications of brenetafusp, making it a valuable asset in Immunocore’s pipeline.

• Abstract Number – 618MO
• Abstract Type - Mini oral session
• Indication - HR+ HER2- metastatic breast cancer
• Class and target – Next generation CDK4 and CDK2-selective inhibitor

Title: Pfizer’s Next-Gen CDK Inhibitors, PF-07220060 in combination with PF-07104091, are poised to redefine HR+/HER2− metastatic breast cancer treatment 

Executive Summary –-The groundbreaking results from the Phase I/IIa study of PF-07220060, a first-in-class, next-generation CDK4-selective inhibitor, in combination with endocrine therapy (ET) for patients with HR+/HER2− mBC, will be a highlight at ESMO 2024. 

Main Content –  

HR+/HER2- breast cancer accounts for approximately 70% of cases, making it the most common subtype, with approximately 208,400 incident cases of HR+/HER2– Breast Cancer in the US, in 2023. Endocrine therapy has been the cornerstone of managing HR+/HER2− mBC, even in patients with visceral disease, offering targeted and effective treatment options, over the past decade. The Phase I/II trial evaluating the combination of two next-generation inhibitors—PF-07220060, a CDK4-selective inhibitor, and PF-07104091, a CDK2-selective inhibitor, represents an innovative approach to treating HR+ HER2- metastatic breast cancer (MBC) and advanced solid tumors. This trial seeks to build upon the success of CDK4/6 inhibitors, which have revolutionized the treatment landscape for HR+ MBC but face challenges as patients progress on current therapies.

The novel CDK4 inhibitor, PF-07220060, when combined with endocrine therapy, has demonstrated a favorable safety profile and strong response rates in heavily pretreated patients with HR+/HER2- metastatic breast cancer who had progressed on prior CDK4/6 inhibitors, regardless of mutation status. These promising findings from a Phase I/IIa trial (NCT04557449) were already presented at the 2024 ESMO Breast Cancer Congress.

As the first next-generation CDK2/4 inhibitors enter the clinical arena, competition is intensifying. The CDK4/6 inhibitor market is currently dominated by IBRANCE, KISQALI and VERZENIO. In first line setting, both VERZENIO and IBRANCE did not meet statistical significance during final overall survival analysis, giving way to KISQALI, whereas in relapsed/refractory setting, both VERZENIO and KISQALI achieved overall survival endpoint, however IBRANCE failed in this segment too, which gives us a reason to believe why Pfizer is looking forward to a new class. Additionally, IBRANCE is also expected to lose patent by 2027. 

• Abstract Number – 1706P
• Abstract Type – Poster session
• Indication - Advanced or metastatic clear-cell renal cell carcinoma (ccRCC)
• Class and target – Monoclonal antibody targeting CD200R1

Title:  The Next Wave of Immunotherapies: 23andMe's is showcasing its promising updated results from its first-in-class anti-CD200R1 antibody, 23ME-00610 in metastatic ccRCC setting. 

Executive Summary: 23andMe's novel anti-CD200R1 monoclonal antibody, 23ME-00610, offers a unique immunotherapy approach for advanced clear-cell renal cell carcinoma (ccRCC) by targeting immune suppression in the tumor microenvironment. Preliminary data from its Phase I/II trial shows promise with early signs of efficacy and a manageable safety profile, with additional efficacy data expected at ESMO 2024. 

Main Content –  

The ccRCC treatment landscape is highly competitive with established standard treatments dominating the market, including immune checkpoint inhibitors targeting PD-1/PD-L1, such as OPDIVO and KEYTRUDA, in combination with VEGF inhibitors (e.g., axitinib, cabozantinib). However, despite these options, a significant portion of patients do not achieve long-term responses, creating a niche for next-generation immunotherapies like 23ME-00610.

23andMe’s first-in-class anti-CD200R1 monoclonal antibody, 23ME-00610, by targeting CD200R1, offers a complementary approach to PD-1/PD-L1 blockade, potentially reversing immune suppression in the TME and enhancing T cell responses. The drug is currently being evaluated in a Phase I/II trial for its efficacy and safety in patients with advanced or metastatic clear-cell renal cell carcinoma

In Phase II data presented at the ASCO in June 2024, monotherapy 23ME-00610 demonstrated a continued acceptable safety and tolerability profile and preliminary evidence of clinical benefit in neuroendocrine and ovarian cohorts, including one confirmed partial response in a patient with well-differentiated pancreatic neuroendocrine cancer. Additionally, data showed early evidence pointing to CD200 as a potential tissue-based biomarker. The company will now present additional preliminary clinical data, including efficacy data, for the clear-cell renal-cell carcinoma in the Phase IIa portion of its ongoing Phase I/IIa clinical trial evaluating 23ME-00610 at the ESMO 2024. 

As patients with ccRCC develop resistance to both ICIs and VEGF inhibitors, 23ME-00610 could be positioned as a second-line or later-line therapy, filling an unmet need in this space. Moving forward, further trials will help clarify its optimal use, and define its place in the market amid growing competition. Other companies developing novel immunotherapies for ccRCC include AstraZeneca, Bristol-Myers Squibb, and Roche, which are all exploring next-generation ICIs, bispecific antibodies, and other immunomodulatory approaches. 

• Abstract Number – 574P
• Abstract Type – Poster 
• Indication - Advanced colorectal cancer (CRC)
• Class and target – PD-1/IL-2 bispecific antibody 

Title: A new hope for advanced CRC patients with failed immunotherapies – Innovent’s Breakthrough PD-1/IL-2 bispecific molecule, IBI363, set for ESMO 2024 Reveal

Executive Summary- : Innovent Biologics is preparing to unveil Phase I clinical data for IBI363, a first-in-class bispecific antibody fusion protein that targets PD-1 and IL-2α (CD25) positive T cells in advanced CRC.

Main Content –  

CRC is the third most commonly diagnosed cancer and the second leading cause of cancer death, with approximately 153,700 incident cases in the US, in 2023, as per DelveInsight’s estimates. Nearly 60% of patients diagnosed with CRC develop distant metastases during their disease course, and the prognosis of metastatic CRC is poor, with a 5-year survival rate of less than 20%. 

IL-2 is one of the earliest immunotherapies approved for cancer treatment; however, the safety and efficacy of IL-2 therapy have not been satisfactory. Innovent Biologics’s IBI363, a novel PD-1/IL-2 bispecific molecule, designed to selectively activates PD-1 and CD25 positive T cells by cis-activating IL-2, with the potential to significantly decrease toxicity related to IL-2 and potentially overcome immunotherapy resistance. IBI363 has shown promising anti-tumor activity in various tumor-bearing models, including PD-1-resistant and metastatic models, with a good safety profile in preclinical studies. Clinical trials are ongoing in China, the United States, and Australia to assess its safety, tolerability, and preliminary efficacy in advanced malignancies. 

For subjects with advanced CRC who have failed standard chemotherapy, the ORR for existing treatments is only 1% ~ 4.7%, and the median overall survival is only 6 ~ 9 months. So far, IBI363 has shown acceptable tolerability and manageable safety profiles in IO failed melanoma, non-small cell lung cancer, cold tumors such as colorectal cancer and several other tumor types. These results already presented at the ASCO 2024 suggest the broad-spectrum anti-tumor effect of IBI363. 

Further studies investigating IBI363 in combination with standard treatments in advanced CRC have been initiated. With the US FDA IND approval, Innovent Biologics plans to initiate a Phase II study in the US in 2024. 

Top 10 most awaited first-in-class abstracts have been summarized below: