ASCO 2024 ran from May 31-June 4 in Chicago, IL, bringing together physicians, academics, and industry to share data and discuss cutting edge treatments in oncology.
Below, Adelphi’s Oncology Task Force breaks down key news from some of the biggest players in oncology, including Merck, BMS, Roche/Genentech, Johnson & Johnson, AstraZeneca, Pfizer, Novartis, Amgen, Lilly and GSK. In our analysis, we cover a wide array of tumour types and multiple hot topics including the exciting showdown in multiple myeloma (with Johnson & Johnson, BMS, and potentially GSK ready to grow in the space), the race for novel KRASG12C inhibitors, continued interest in radioligands, and growth of established brands like Keytruda and Opdivo.
MERCK’S 3-PRONGED ONCOLOGY APPROACH: DATA ON KEYTRUDA, MODERNA V940 COMBINATION and TROP2-ADC
Oncology powerhouse Merck presented several Keytruda abstracts at ASCO 2024, including:
- KEYNOTE-966 (biliary tract cancer)
- KEYNOTE-859 (HER-2negative gastric or GEJ cancer)
- KEYNOTE-A39/EV-302 PROs (mUC)
- KEYNOTE-671 (Stage II, IIIA or IIIb NSCLC)
- KEYNOTE-224 (HCC)
- KEYNOTE-629 (cSCC)
Merck particularly highlighted results for mRNA-4157 (V940, Moderna) in combination with Keytruda in high-risk Stage III/IV melanoma. The Ph2b KEYNOTE-942/mRNA-4157-P201 results, presented during a rapid oral abstract session, showed a benefit in recurrence-free survival and reduced the risk of recurrence or death by 49% compared to Keytruda alone.
Beyond the blockbuster flagship brand Keytruda, Merck also shared results of sacituzumab tirumotecan (sac-TMT), an investigational TROP2-directed ADC, in previously treated locally recurrent or metastatic TNBC.
In other interesting news, ivonescimab, a bispecific antibody from China, out-licensed to Summit Therapeutics, beat Keytruda in a H2H trial in NSCLC, setting the stage for the potential game-changing paradigm to gain approval.
BMS PROVIDES ADDITIONAL OPDIVO DATA, BUT FUTURE UNCERTAIN FOR KRAZATI
Much of the data at ASCO 2024 from oncology powerhouse BMS was focused on Opdivo and its combination regimens. Notably, BMS shared data on:
- Opdivo + Yervoy vs. Lenvima or Nexavar in CheckMate-9DW (unresectable hepatocellular carcinoma) (HCC)
- Three-year follow-up data of Opdualog (nivolumab + relatlimab) in previously untreated metastatic or unresectable melanoma
- Five-year survival data from the Ph3 CheckMate-9LA trial of Opdivo + Yervoy with chemotherapy vs. chemotherapy in NSCLC
- Four-year follow-up data from the Ph3 CheckMate-816 trial of neoadjuvant Opdivo plus chemotherapy in resectable NSCLC
- Exploratory analysis from the Ph3 CheckMate-77T trial of Opdivo in perioperative resectable NSCLC
The company also shared multiple subgroup analyses of the Ph1/2 TRANSCEND CLL 04, Ph1 TRANSCEND NHL 001 (MCL cohort) and Ph2 TRANSCEND FL studies showing durable responses for Breyanzi in CLL, MCL and FL.
BMS also lauded results of the Ph3 KRYSTAL-12 study of Krazati as a monotherapy in patients with KRASG12C-positive NSCLC. However, analysts and members of the scientific community were less impressed by the PFS data, which only offered 1.65 months of additional PFS.
GENETECH SEES POSITIVE ENERGY SURROUNDING TIRAGOLUMAB, DESPITE MIXED NEWS
Roche/Genentech shared positive data for TIGIT tiragolumab in esophageal squamous cell carcinoma (ESCC), improving both PFS and OS when combined with Tecentriq in the SKYSCRAPER-08 trial. However, some criticized the trial, which utilized chemotherapy (no longer the SOC) as the comparator. A checkpoint inhibitor such as Merck’s Keytruda or BMS’s Opdivo was not included in the control arm.
Another trial of tiragolumab did not show any benefit to PFS in patients with non-small cell lung cancer (NSCLC). Last year, after an accidental data drop, the company announced tiragolumab also failed to improve overall survival for locally advanced or metastatic NSCLC.
In other news, Genentech recently announced FDA has accepted the company’s NDA for inavolisib and granted Priority Review. Inavolisib in combination with Ibrance and fulvestrant was evaluated in adult patients with PIK3CA-mutated, HR+/HER2-, locally advanced or metastatic breast cancer, following recurrence on or within 12 months of completing adjuvant endocrine treatment.
The Priority Review is based on the positive Phase III INAVO120 results, which showed the inavolisib-based regimen more than doubled progression-free survival, reducing the risk of disease worsening or death by 57% compared to palbociclib and fulvestrant alone (15.0 months vs. 7.3 months in the first-line setting). Overall survival (OS) data were immature at the time of primary analysis, but a clear, positive trend was observed.
The agent could ultimately join Piqray and Truqap as an option for PIK3CA-mutated breast cancer patients.
JOHNSON & JOHNSON PRESENTS DIVERSE DATA ACROSS TUMOR TYPES
J&J presented a total of 19 abstracts at ASCO 2024, primarily focusing on lung, prostate, bladder and multiple myeloma.
In multiple myeloma, where J&J placed the most focus, the company is setting the stage to gain market dominance over incumbent BMS by 2030. At ASCO 2024, J&J presented multiple myeloma data from:
- The Ph3 PERSEUS trial assessing DARZALEX FASPRO
- The Ph3 CARTITUDE-4 study of Carvkyti as 2L therapy
- The Ph2 CARTITUDE-2 study of Carvykti with lenalidomide maintenance
- Updated analysis with longer-term follow-up from the Ph1/2 MajesTEC-1 study of Tecvayli in R/R MM patients receiving prophylactic tocilizumab, plus long-term follow-up data
- Initial data from the safety run in from the Ph3 MajesTEC-7 study of Tecvayli
- First data from the Ph2 OPTec study looking at outpatient step-up administration of Tecvayli
Beyond MM, Johnson & Johnson also presented data for amivantamab in NSCLC, Rybrevant and Lazertinib in NSCLC, JNJ-69086420 in mCRPC, and data on Balversa in relation to FGFR alterations in bladder cancer.
ASTRAZENECA’S AMBITIOUS GOAL IN LUNG, AND A NEW STRATEGY FOR ENHERTU
Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca said: “Our plenary data at ASCO show the pioneering role of our medicines in curative-intent lung cancer treatment and highlight progress toward our continued ambition to have a medicine for more than half of all patients treated for lung cancer by 2030.”
AZ isn’t new to setting big goals. Recall, just last month the company announced ambitions to generate $80 billion in annual revenue by 2030, up from $45 billion in 2023.
In line with their lung ambitions, AZ presented positive data on Tagrisso in unresectable stage III NSCLC (with a standing ovation for their impressive PFS benefit), as well as Imfimzi in limited-stage SCLC.
The company also showed interesting data for Enhertu in metastatic breast cancer, demonstrating positive PFS benefit in HER2-low patients. This data, which could expand the eligible patient population, creates an interesting discussion regarding current diagnostics for HER2 and how HCPs classify different patient types. An understanding of this classification will be essential in predicting the future success of Enhertu.
PFIZER TALKS ADCETRIS, IMPRESSIVE ALK+ NSCLC DATA
Along with partner Takeda, Pfizer shared data on their ADC Adcetris in both Hodkin’s Lymphoma (HL) and Diffuse large B cell lymphoma (DLBCL). In HL, the companies shared that Adcetris, in combination with several other cancer treatments such as etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD) vs. SOC, showed superior PFS (at 48 months) and significantly improved safety as assessed by treatment-related morbidity (TRMB). In DLBCL, the Adcetris regimen reduced the risk of death by 37%, compared to chemotherapy alone. The OS benefit was consistent across levels of CD30 expression.
Perhaps most notable was the news of Lorbrena in ALK+ NSCLC. The data showed an 81% reduction in the rate of disease progression or death, compared to XALKORI; 60% of patients treated with Lorbrena were alive without disease progression after five years, compared to 8% on the XALKORI treatment arm. Lorbrena also showed a 94% reduction in the risk of developing intracranial (IC) progression.
Finally, Pfizer shared some early Ph1 data on their KAT6 inhibitor (PF-07248144), showing a 38% ORR in ER+/HER2- breast cancer patients who had progressed on a CDK4/6 inhibitor.
NOVARTIS AIMS TO DISPLACE TKIs IN CML, PUSH KISQALI INTO eBC
Much of Novartis’ focus at ASCO 2024 centred on Scemblix and Kisqali.
Novartis presented potentially paradigm-shifting Scemblix data in frontline CML, creating the potential to displace TKIs from their decades-long SoC position. The Ph3 data shared showed clinically meaningful and statistically superior benefit vs. TKIs in efficacy (MMR 67.7 vs. 49.0%) with a more favorable tolerability profile. Notably, the CML study used a unique endpoint – molecular response rate (MMR) – which, for chronic diseases CML, may paint a better picture of disease progression than OS, PFS or rPFS.
There was also significant buzz regarding Kisqali, which has an anticipated US PDUFA date this summer in early breast cancer. Data from the NATALEE trial showed a 28% risk reduction in invasive disease-free survival (iDFS) in a subgroup of patients with node-negative (N0) disease at high risk of occurrence. GlobalData forecasts are projecting a near 50% increase in Kisqali breast cancer revenue in the next year, partially driven by the expanded indication into early breast cancer.
The radioligand therapy leader also shared data for Pluvicto in mCRPC and Lutathera data in GEP-NETs.
AMGEN FOCUSES ON NEW BISPECIFIC T-CELL ENGAGER IMDELLTRA
Amgen presented a total of 17 abstracts at ASCO 2024, covering assets including the newly FDA-approved bispecific t-cell engager Imdelltra in SCLC and NEPC, as well as OS data for Lumakras plus Vectibix in metastatic colorectal cancer.
Of interest, BMS presented design details regarding their KRASG12C inhibitor in NSCLC. Recall, Amgen’s KRAS confirmatory results were rejected by the FDA as uninterpretable. It remains to be seen if the BMS agent will ultimately gain a positive response from FDA.
LILLY TARGETING KRAS IN NSCLC, PLUS VERZENIO DATA AND MORE
Lilly presented a number of abstracts on CDK4/6i Verzenio, including data in HR+/HER2- aBC, HER+/ER2- eBC and mCRPC. The data from the CYCLONE trial in mCRPC was disappointing, failing to reach statistical significance when combined with Zytiga. Lilly has therefore announced that they will not continue to develop Verzenio for mCRPC, but has set their sights on radioligand development in this space with PNT2002, acquired with Point Biopharma.
Along with BMS and Amgen, Lilly is also developing a KRASG12C inhibitor. Results from a Ph1/2 study of olomorasib showed a positive ORR of 35% in patients with non-CRC solid tumors, while results of Keytruda + olomorasib showed an ORR of 77% in NSCLC patients.
Lilly also shared positive data of their RET inhibitor, Retevmo, in pediatric solid tumor patients, NSCLC and MTC and their oral SERD, Imlunestrant, in ER+/HER2- aBC.
GSK GETS POTENTIAL SECOND WIND FOR BLENREP
GSK continued to rebuild the case for ADC Blenrep in multiple myeloma, sharing positive data from the DREAMM-7 and DREAMM-8 Ph3 studies. In DREAMM-7, Blenrep beat J&J’s Darzalex by 59% in PFS, while, in the DREAMM-8 trial, Blenrep cut the risk of progression by 48% when compared with Takeda’s Velcade in their respective combinations with Pomalyst and dexamethasone.
Investigators/presenters for the trial argued that these results support Blenrep’s return to market, initially triggered by a failed monotherapy Ph3 trial. If re-approved, Blenrep will be positioned to compete against J&J’s Carvykti and BMS’s Abecma.
Outside of Blenrep, GSK also showed positive results of Jemperli in dMMR locally advanced rectal cancer.