SAN FRANCISCO – The 43rd annual JP Morgan Healthcare Conference continued here on Tuesday, with drug developers talking up the blockbuster potential of certain precision oncology products and providing updates on upcoming pivotal trials and new pipeline products.
Below are short summaries of presentations from select companies that provided updates on their precision medicine and diagnostic pipelines on Tuesday.
Novartis
Novartis said that its CDK4/6 inhibitor Kisqali (ribociclib) now has a 52 percent new-to-brand prescription share in the early-stage breast cancer setting.
This comes just months after the US Food and Drug Administration approved Kisqali plus an aromatase inhibitor as an adjuvant treatment for hormone receptor (HR)-positive, HER2-negative stage II and III early breast cancer at high risk of recurrence.
"Given the trajectory that we're now seeing in early breast cancer, we believe Kisqali can be an $8 billion-plus medicine," Novartis CEO Vas Narasimhan said.
And for its prostate-specific membrane antigen (PSMA)-targeted prostate cancer radioligand therapy Pluvicto (lutetium vipivotide tetraxetan), Novartis believes the drug could reach $5 billion in peak sales across all treatment lines. The drugmaker is expecting to receive regulatory approval in 2025 for Pluvicto as a treatment for metastatic castration-resistant prostate cancer (mCRPC) patients who have not received prior taxane-based chemotherapy. Novartis also anticipates a data readout for Pluvicto in the hormone-sensitive prostate cancer setting this year.
Beyond Pluvicto, Narasimhan also provided updates on additional radioligand therapies that Novartis is advancing, including those that involve the alpha-emitting radioisotope actinium. For instance, the firm's actinium-labeled prostate cancer radioligand Ac-PSMA-617 is expected to enter Phase III clinical trials for mCRPC during the first half of 2025.
Novartis is also focusing on early-stage radioligand assets, including its lutetium-labeled radioligand therapy dubbed FXX489, which the drugmaker is evaluating for certain solid tumor patients, including those with breast, pancreatic, lung, and colorectal cancer.
"We have a number of other emerging radioligand therapies, including a HER2 radioligand therapy, which we are now moving into the clinic in 2025," Narasimhan said, explaining that the firm is taking a dual approach by using radiopharmaceuticals to go after both new, unique tumor targets that can only be addressed by this type of therapy as well as more established targets, like HER2, that have traditionally received antibody-drug conjugates. For these more established targets, he said, "we think we can potentially get a better therapeutic index with a radioligand therapy."
As Novartis continues to invest in its radiopharmaceutical pipeline, including through acquisitions like its recent licensing of Ratio Therapeutics' SSTR2-directed radiopharmaceutical capabilities, it is also looking to broaden the accessibility of these treatments.
"A lot of this now comes down to: 'How can we move this from an academic and large hospital setting further and further into the community?'" Narasimhan said, adding that the company has been focused on building out stronger referral networks to radiation oncology specialties while also helping community oncologists build out their ability to administer radiopharmaceuticals in their own practices.
"If you play the long game, the way I think of it is [getting] radioligand therapy … to be like chemo, where it's just given in the community," he said, adding that Novartis expects to achieve this goal and resolve radiopharmaceutical access barriers by 2030.
Relay Therapeutics
Relay Therapeutics said it will begin a pivotal Phase III trial of its investigational PI3Kα inhibitor RLY-2608 with fulvestrant in patients with advanced PIK3CA-mutated, hormone receptor (HR)-positive, HER2-negative breast cancer in 2025. The Cambridge, Massachusetts-based firm plans to meet with the US Food and Drug Administration to discuss a clinical trial plan before launching the study.
RLY-2608 is designed to target the mutant isoform of PI3Kα, a member of the PI3K/AKT/mTOR (PAM) pathway encoded by the PIK3CA gene. Relay and other drugmakers believe a PI3kα inhibitor that can home in on the mutant protein could avert hyperglycemia and other on-target adverse effects associated with drugs in this class, particularly Novartis' Piqray (alpelisib).
Relay reported results from the first-in-human Phase I ReDiscover trial of RLY-2608 in December, showing that patients with advanced HR-positive, HER2-negative breast cancer harboring PIK3CA mutations on RLY-2608 and fulvestrant lived a median 9.2 months, and 66 percent were alive at six months without signs of progression. A subset of patients treated with RLY-2608 as a second-line therapy survived 11.4 months without disease progression or death. Overall, 46.9 percent of patients had hyperglycemia. However, just 3.1 percent of patients had grade 3 hyperglycemia.
Those results compare favorably against the typical five-and-a-half months of progression-free survival associated with standard-of-care therapy. Even though this was not a head-to-head comparison, according to Relay President and CEO Sanjiv Patel, this data still gave the company confidence to proceed to a pivotal trial.
In the planned Phase III trial, Patel said Relay will compare RLY-2608 to AstraZeneca's AKT inhibitor Truqap (capivasertib) in patients who have previously received a CDK4/6 inhibitor and will aim to market the drug as a second- or later-line therapy. Patients in the experimental arm will receive a 600 mg dose of RLY-2608 twice per day with fulvestrant, while those in the comparator arm will receive 400 mg Truqap twice a day for four days on, three days off per week plus fulvestrant. Investigators will track progression-free survival as the primary endpoint and overall survival, objective response rate, duration of response, and quality of life as secondary endpoints.
Patel estimated that approximately 13,000 patients per year in the US have HR-positive, HER2-negative metastatic breast cancer with a PIK3CA mutation, representing a "very large commercial opportunity."
Relay is also testing RLY-2608 in a triplet combination with Novartis' CDK4/6 inhibitor Kisqali (ribociclib) and fulvestrant in a Phase I trial, and plans to begin another triplet combination clinical trial of RLY-2608 with fulvestrant and Pfizer's investigational CDK4/6 inhibitor atirmociclib.
Beyond breast cancer, Relay is exploring RLY-2608 as a treatment for PI3Kα-driven vascular malformations and expects to begin a clinical trial in the first quarter of 2025. The firm also has plans to launch clinical programs in NRAS-driven solid tumors and Fabry disease in the second half of 2025.
Erasca
After acquiring two new RAS-targeting candidates in 2024 and ending development of its ERK inhibitor, EGFR inhibitor, and first pan-KRAS inhibitor, Erasca has announced its plans to bring two new candidates, ERAS-0015 and ERAS-4001, into clinical trials this year.
The firm's lead candidate, pan-RAF inhibitor naporafenib, has also entered a Phase III trial, called SEACRAFT-2, in combination with Novartis' MEK inhibitor Mekinist (trametinib) in previously treated metastatic NRAS-mutant melanoma. Initial data from that study are expected in the second half of 2025, said Erasca CEO Jonathan Lim.
The SEACRAFT-2 trial has two stages, Lim said. In the first stage, researchers will assess two dose levels of the naporafenib-Mekinist combination against Mekinist alone in NRAS-mutant melanoma, and in the second stage, they will compare the naporafenib-Mekinist dose selected in stage 1 to physician's choice of treatment with Mekinist monotherapy or chemotherapy alone in these patients. The data expected to read out this year will be from the first stage, the dose-optimization portion of the trial.
"The standard of care for NRAS melanoma, which is a very aggressive disease with high unmet need and no targeted therapies that are approved for this indication, is only chemotherapy," Lim said, estimating that with chemo response rates are around 7 percent and median progression-free survival is around 1.5 months. "For naporafenib and trametinib, we have a potential to be first to market in this high unmet need area."
In the second quarter, Erasca expects to file an investigational new drug (IND) application with the US Food and Drug Administration for both its pan-RAS molecular glue ERAS-0015 and pan-KRAS inhibitor ERAS-4001. Lim noted that the company will file an IND for ERAS-0015 first in Q2.
Erasca will begin a Phase I trial of ERAS-0015 in RAS-mutant solid tumors and a Phase I trial of ERAS-4001 in KRAS-mutant solid tumors this year. Initial monotherapy data from these studies is expected in 2026.
Lim noted that the firm's main competitor for ERAS-0015, the pan-RAS therapy, is Revolution Medicines' daraxonrasib, which has recently entered a registrational Phase III trial.
"The scientific bar for working on a pan-RAS molecular glue is very high, so there's a scarcity issue within this class," Lim said. "We've learned a lot from [Revolution Medicine's] clinical data in pancreatic cancer and non-small cell lung cancer, but being second [in development] in an area of high unmet need, across pancreatic, lung, and other tumor types, is a good place to be."
Syndax Pharmaceuticals
Syndax Pharmaceuticals is preparing for a potential second approval in 2025 for its menin inhibitor Revuforj (revumenib).
Revuforj gained its first US approval in November as a treatment for adult and pediatric patients 1 year and older with relapsed or refractory acute leukemia harboring KMT2A translocations. This year, Syndax expects to file a supplemental new drug application (sNDA) to expand the indication to patients with relapsed or refractory NPM1-mutant acute myeloid leukemia (AML).
Syndax CEO Michael Metzger said the firm will publish previously reported pivotal trial data of Revuforj in NPM1-mutant leukemia and submit it as part of an sNDA to the US Food and Drug Administration and to the National Comprehensive Cancer Network in the first half of 2025. If that timeline is met, the potential approval in NPM1-mutant AML would occur by the end of 2025.
"NPM1 [mutations] are a big subset of all AML, about 30 to 35 percent [of patients]," Metzger said. "We've seen good uptake of [Revuforj] and utilization across the board in patients with KMT2A [leukemia], but we're also seeing some interest in NPM1, as well."
The firm is also pushing into frontline treatment with Revuforj in 2025, with plans to begin two trials in frontline KMT2A-rearranged and NPM1-mutant leukemias.
In Q1, Syndax expects to begin a pivotal trial, called HOVON, evaluating Revuforj with venetoclax and azacitidine as a frontline treatment for KMT2A-rearranged and NPM1-mutant acute leukemia patients who are unfit for standard chemotherapy.
"This is an area of very high unmet medical need," Metzger said. "A majority of patients [enrolled] will be NPM1 patients, and we will be allowing KMT2A patients, but KMT2A patients are generally fit [to receive chemo]. This trial gives us probably the fastest route to the frontline, and we are considerably ahead of any competition to get there."
The firm will also begin another frontline trial this year of Revuforj with intensive chemotherapy for KMT2A-rearranged and NPM1-mutant acute leukemia patients who are fit to receive chemo.
"It's very important to be first to market. You have this experience that physicians build, they get comfortable, they get familiar with the drug, and it sets a very high bar for the next agent," Metzger said. "[The next molecule] has to be extremely differentiated, and, frankly, we don’t see that in any of the competitive molecules that have presented data to date. Most of them are far behind us, and in terms of their data, we don’t see anything that makes them more than 'me too' products at this point."
AstraZeneca
AstraZeneca is anticipating an expansion of its Enhertu (trastuzumab deruxtecan) franchise in 2025, as it expects the HER2-targeted antibody-drug conjugate it developed with Daiichi Sankyo to be approved as a second-line therapy in chemotherapy-naïve, HER2-low or -ultralow, hormone receptor-positive metastatic breast cancer as well as readouts from a trio of clinical trials.
With its regulatory filing with the US Food and Drug Administration in October 2024, which is based on results from the Phase III DESTINY-Breast06 trial, AstraZeneca hopes to further expand the breast cancer subtype once known as HER2-negative to also encompass ultralow HER2 expression. The firm also expects a corresponding update to National Comprehensive Cancer Network guidelines in the coming months.
In the first half of 2025, the company anticipates data from the Phase III DESTINY-Breast11 trial, in which researchers are comparing Enhertu to standard therapy with paclitaxel, trastuzumab, and Roche's anti-HER2 monoclonal antibody Perjeta (pertuzumab) as a neoadjuvant therapy in patients with high-risk, HER2-positive early non-metastatic breast cancer.
The drugmaker also will be looking for results from the Phase III DESTINY-Breast05 and DESTINY-Breast09 trials in the second half of 2025. DESTINY-Breast05 is exploring Enhertu's efficacy in high-risk, HER2-positive breast cancer with residual invasive disease compared to Roche's anti-HER2 antibody-drug conjugate Kadcyla (trastuzumab emtansine). And in DESTINY-Breast09, AstraZeneca aims to move the drug into the first-line HER2-positive metastatic breast cancer setting by comparing Enhertu with or without Perjeta to the taxane, trastuzumab, and Perjeta drug trio.
AstraZeneca CFO Aradhana Sarin said Enhertu has the potential to replace the drug trio as the standard of care in front-line metastatic HER2-positive breast cancer, adding that it would represent "a significant opportunity with over 65,000 patients globally."
AstraZeneca is also expecting data on the TROP2-directed ADC Datroway (datopotamab deruxtecan) in locally recurrent inoperable or metastatic triple-negative breast cancer from TROPION-Breast02 in the first half of 2025 and for Datroway plus its checkpoint inhibitor Imfinzi (durvalumab) in neoadjuvant and adjuvant triple-negative and HR-low, HER2-negative breast cancer in TROPION-Breast04 in the second half of 2025.
Adaptive Biotechnologies
Adaptive Biotechnologies is hoping to bring its minimal residual disease (MRD) testing business to profitability in 2025, CEO Chad Robins said.
Increases in both volume and average selling price should drive growth on the clinical testing side, while growth in testing for pharma could come from new studies using the company's ClonoSeq assay as an endpoint, enabled by a recent US Food and Drug Administration committee decision.
In April, the FDA's Oncologic Drugs Advisory Committee unanimously voted to allow MRD as an early endpoint in myeloma clinical trials. "It's resonating across the industry," Robins said. "The use of a biomarker as primary endpoint is really special because it will provide accelerated approvals."
The firm is integrating ClonoSeq ordering with electronic medical record systems — Epic for academic medical centers and Flatiron Health's OncoEMR for the community oncology setting — which it hopes will expand access and ease of use. The firm expects EMR-embedded orders to grow from 20 percent to more than half of all orders.
Adaptive also announced on Tuesday an exclusive strategic commercial partnership with NeoGenomics to cross-promote ClonoSeq with NeoGenomics' diagnostic services.
The company anticipates a ClonoSeq ASP of $1,300 per test on average in 2025, representing a 24 percent increase from 2023. Part of that is driven by Medicare setting a new gap-fill rate of approximately $2,000 per test, a 17 percent increase from the previous rate, which will help with both Medicare payments and negotiations with commercial payors.
Adaptive also expects to save money on testing costs by transitioning its sequencing fleet. Instead of 33 Illumina NextSeq mid-throughput instruments, it will run two Illumina NovaSeq X instruments, beginning in the second half of the year.