The annual meeting of the American Society of Clinical Oncology draws approximately 50,000 people to McCormick Place in Chicago for an in-depth look at the latest advances in cancer care.
Big Pharma always makes big news at ASCO, and this year was no exception, as both Gilead Sciences and AstraZeneca released data updates that could have a big impact on their respective breast cancer drugs. But some clinical-stage biotech companies have also made headlines, releasing new data showing that their experimental therapies could offer patients new treatment options. This year’s presentations reflect developments in cell therapy research. In addition to approved CAR T therapies, several companies have provided data on their off-the-shelf alternatives. Below is a recap of some news highlights from the conference.
breaking breast cancer news
Two years ago, Gilead Sciences bought Immunomedics for $21 billion, betting that its then-recently approved breast cancer drug Trodelvy could be a blockbuster. Preliminary approval of antibody-drug conjugate covers rare but aggressive triple-negative breast cancer. At ASCO, Gilead reports phase 3 trial data in HR-positive and HER2-negative breast cancer, a more common disease type. Although initial analysis showed that the study met its primary goal of measuring progression-free survival, with a median improvement of six weeks compared to chemotherapy. Overall survival data are not yet mature.
Véronique Dieras, an oncologist at the Marquis de Eugene Center in Rennes, France, acknowledged that Gilead’s drug met its main research goals. But she added that it was unclear whether that would be enough to provide patients with a better quality of life. “Maybe my underlying concern is that when we look at the results of the phase 3 studies, we have to ask about the magnitude of the benefit and whether it’s clinically meaningful,” she said.
At the same time, partners Published data by AstraZeneca and Daiichi Sankyo could significantly expand the use of their antibody-drug conjugate Enhertu. The approval of this product currently covers HER2-positive breast cancer. Patients with low HER2 levels are classified as HER2 negative, based on the idea that drugs targeting this HER2 gene signature will not work in patients with low levels of the protein. Drug data reported by ASCO suggest otherwise.
Phase 3 study recruiting “HER2-low” patients; primary objective is to assess progression-free survival. On this measure, the Enhertu group lived an average of 10.1 months, compared with 5.4 months for those who received chemotherapy. Jane Meisel, a professor of hematology and oncology at Emory University and an ASCO breast cancer specialist, described the results as “a change in practice.”
Enhertu does carry some risk of lung toxicity. The study’s lead investigator, Shanu Modi of Memorial Sloan Kettering Cancer Center, acknowledged these risks, but said clinicians could monitor for these adverse effects and manage them as they arise.
Advances in BCMA-targeted drugs
partner Johnson & Johnson and Legend Biotech received FDA approval for Carvykti last year, a CAR T-cell therapy that treats multiple myeloma by targeting a protein called B-cell maturation antigen (BCMA). The decision is based on Phase 1b/2 data.The legend now has long-term data Showing durability of the treatment after more than two years, these results were presented at ASCO.
Among patients with multiple myeloma who had received extensive treatment and had disease relapse or did not respond to earlier treatment, Legend reported an overall response rate of 98% at a median follow-up of 28 months. During the follow-up period, there were no data on median progression-free survival or median overall survival, which the company said indicates long-term durability of response and survival in patients treated with the drug.
Additionally, another study is underway evaluating Carvykti as an early treatment option in 20 patients with multiple myeloma who have received one to two lines of prior therapy and whose disease cannot be treated with Revlimid, a myeloma care standard medicine. At a median follow-up of 17.1 months, Legend reported an overall response rate of 95%; 90% of patients achieved complete remission or better.
Arcellx is a relative latecomer to BCMA in multiple myeloma, trailing last year’s approval of Carvykti and Bristol Myers Squibb drug Abecma.but Arcellx brings a different technology to the BCMA search – synthetic binding domains it calls D-Domains– it proposes Early Phase 1 Data The ASCO suggested its approach could provide better efficacy.
A total of 31 patients from the Phase 1 extension study were evaluable for efficacy and safety at least one month after treatment. As of the May 3 deadline, Arcellx reported a 100% overall response rate for its therapy CART-ddBCMA. The complete response rate was 71% (22 of 31 patients). Toxicity was manageable, and all problems were resolved with standard care at both dose levels tested. There were no cases of neurotoxicity or Parkinson’s symptoms, Arcellx said.
In a research note, William Blair analysts Raju Prasad and Sami Corwin wrote that the strong clinical activity and durability of the Arcellx therapy de-risked the company’s technology. If the patient outcomes recruited by this pivotal study are more representative of the relapsed and refractory multiple myeloma patient population — similar to those enrolled in the Legend study — William Blair believes that a successful clinical trial could make Arcellx a BCMA CAR T therapy leader in.
Adicet identifies key data for off-the-shelf CAR T
Off-the-shelf cell therapies are seen as key to making these therapies more widely available, in part because the process of personalizing cell therapy using a patient’s own T cells is lengthy and expensive. Adicet Bio continues to publish data supporting its approach, which uses a rare type of T cells called gamma delta T cells, which are derived from healthy donors. Last year, the biotech reported preliminary Phase 1 data from four patients showing that its approach is workingAt ASCO, Adicet provided an update on the study enrolling patients with advanced B-cell non-Hodgkin lymphoma.
As of May 31st data cutoff, Adicet data now from a total of eight patients. In this cohort of four treatment-experienced patients, Adicet had an overall response rate of 75% for ADI-001, and complete responses were achieved at all dose levels. Of the three patients who had previously relapsed after receiving autologous CAR T therapy, Adicet reported that they all responded to ADI-001. In addition to the manufacturing advantages of off-the-shelf therapies, Adicet is designed to provide safety advantages. The company reported no dose-limiting toxicities, nor any immune response or neurological problems associated with CAR T therapy. Adicet said it expects to finalize the recommended Phase 2 dose in the second half of this year; at least one study that could support the registration application could begin in the first half of 2023.
Using mRNA for Cancer Vaccines
Before BioNTech became known for its Covid-19 vaccine, it was applying its messenger RNA technology to the development of a cancer vaccine. At ASCO, the German company reported preliminary data from a Phase 1 study evaluating autogene cevumeran, a personalized mRNA vaccine based on patient neoantigens. The vaccine is being developed as an adjuvant therapy for pancreatic ductal adenocarcinoma (PDAC) that has been surgically removed. The program is being conducted in partnership with Roche; BioNTech’s cancer vaccine candidate is being tested in combination with Roche’s immunotherapy atezolizumab and chemotherapy.
BioNTech report Preliminary results The treatment was shown to be well tolerated in the 16 patients who received the combination. Neoantigen-specific T cell responses were observed in 50% of patients (8 of 16). At a median follow-up of 18 months, eight patients with a de novo immune response had significantly longer relapse-free survival compared with patients without a vaccine-induced immune response. Based on these early results, the partners are now planning a randomized study to further evaluate the treatment combination in patients with resection of PDAC.
Mirati enters Amgen’s KRAS drug
For a long time, KRAS mutations were thought to be incurable. That changed last year with the FDA approval of Lumakras, an Amgen drug that treats non-small cell lung cancer by targeting a rare KRAS G12C mutation. Mirati Therapeutics aims to provide an alternative to its drug adagrasib, company revealed at ASCO more data Pivotal studies from therapeutic candidates.
Mirati’s drug appears to be comparable to Amgen’s product in terms of efficacy.But Mirati aims to differentiate its drugs by their ability to treat NSCLC transfer to the central nervous system. In 19 evaluable patients, the objective response rate was 32%. Three patients achieved complete remission and three others achieved partial remission. In a research note, William Blair analyst Matt Phipps acknowledged adagrasib’s central nervous system activity, but added that it’s unclear if that’s enough to differentiate the drug, given its similar efficacy data in the general population. Adgrasib is currently under FDA review; a decision is expected in mid-December.
Speaking of non-drugable targets…
The p53 protein is considered the holy grail of drug hunters. It has a variety of anticancer properties but has been an elusive drug target. PMV Pharmaceuticals reports its first clinical data at ASCO showing that its small molecule can drug p53, the results cover a range of tumor types, including ovarian, prostate and pancreatic cancers. In the dose-escalation portion of the Phase 1/2 study, PMV reported an overall response rate of 32% (8 of 25 patients).
Dose-limiting toxicities were reported in two patients at the highest dose, but the company said it is working to identify lower doses that balance safety and efficacy. Clinical trials are continuing to determine doses to advance to Phase 2 testing, which the company expects to begin early next year. Meanwhile, PMV also plans to advance a Phase 1 study to test its drug in combination with checkpoint inhibitors.
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