The American Society of Clinical Oncology (ASCO) annual meeting is the most important meeting in the annual oncology field. The data published in the ASCO annual meeting not only can affect the clinical treatment of cancer patients, the stock price of the relevant pharmaceutical company may also fluctuate strongly with the release of data.
The progress of scientific research is always much slower than most people think. And in the numerous summaries and reports submitted by pharmaceutical companies, there are actually not many studies that really can bring about change in this area. At the same time, there are indeed a number of company studies that can advance the progress of oncology and have a great impact on the clinical treatment of patients. At the same time, some pharmaceutical companies have suffered numerous doubts at this meeting, and share prices have plummeted.
So which company is this year’s ASCO winner?
There is no doubt that Merck East is the biggest winner of this year’s ASCO annual meeting. At this year’s ASCO meeting, Roche has published data on atezolizumab combined with chemotherapy for advanced squamous non-small cell lung cancer (IMpower131). The median progression-free survival of patients in the Atezolizumab combination chemotherapy (carboplatin, albumin-bound paclitaxel) group was 6.3 months compared with 5.6 months in the control group. The program can reduce the risk of tumor progression in patients by 29%, but no survival benefit has been observed.
Squamous non-small cell lung cancer is the final spot for immunotherapy in advanced lung cancer. Although the atezolizumab data is good enough, Merck’s data has an overwhelming advantage: Keytruda combined with chemotherapy can reduce the risk of death by 36% compared with chemotherapy alone in newly diagnosed patients with squamous NSCLC.
JP Morgan analyst Chris Schott said that this study has once again consolidated the dominance of Merck in the NSCLC field. The market for NSCLC is as high as US$12 billion, and Merck in the future will have a market share of 70%. Analysts expect Keytruda’s annual sales to reach $12 billion in the coming years, while Opdivo’s sales are expected to be $9 billion.
For two consecutive years, Loxo Oncology has become the most eye-catching star company in ASCO’s annual meeting. Last year, Loxo announced the data of larotrectinib, with a response rate of 77%. Larotrectinib can target a rare tumor variant: the TRK gene fusion, and another drug Loxo-292, released this year, targets another rare genetic variant: the RET gene fusion.
The Loxo-292 data is also excellent, with a total response rate of 77% for patients with tumors with RET fusion variants. Most of the patients enrolled in the study had lung tumors, including some thyroid cancer and pancreatic cancer. In addition to the RET fusion variant Loxo, 29 patients with medullary thyroid carcinoma with RET mutation were recruited. The response rate of this patient was 45%.
And these patients have a long response time for Loxo-292. There have been no patient recurrences in the patients who responded so far. At the same time, the safety of the drug is also excellent.
In April of this year, BluePrint Medicines released the data of the company’s RET inhibitor BLU-667, but from these data, BLU-667 will be much inferior to Loxo-292: Response to BLU-667 in NSCLC patients with RET fusion mutation The rate was 50%, and the response rate in patients with medullary thyroid carcinoma with RET mutation was 40%.
RET fusion is present in about 2% of lung cancer patients, and 10-20% of thyroid cancer patients and about 60% of medullary thyroid cancer patients also have such tumor mutations. Because of the rare genetic variants that are targeted, even if the drug is successfully approved for marketing, it is still unknown how much market share it can occupy.
But the success of Loxo’s success has been enough to make investors feel confident about the future of this company. Loxo’s stock has risen 30% since the announcement of the ASCO summary last month, and Loxo shares rose by 12% to $211 on Monday, making its market value more than $6 billion. This figure is undoubtedly very high for a company that has not yet listed any drugs. After that, some investors cashed in and left the market, and its stock price fell and remained around $180.
Although the data published by Bluebird Bio at this session of ASCO is enough to prove the potential of BB2121, these figures are still lower than investors’ previous expectations. Bluebird Bio’s CAR-T therapy BB2121 is used to treat multiple myeloma, which in the high-dose group can delay tumor progression by nearly one year, with a median progression-free survival of 11.8 months.
Twenty-one of the 22 patients receiving the highest dose of BB2121 responded and 11 responded completely. The median progression-free survival time was 11.8 months in the highest dose group, while the median progression-free survival time was only 1.9 months in the low-dose group.
However, based on previous data, many people speculated that the therapy could extend the progression-free survival to about 15 months. However, Bluebird CEO Nick Leschly argued that the patients admitted to the group were already in very serious condition. The patients had received an average of 7 treatments and each patient had received at least one stem cell transplant. For these patients, such data is already available. Excellent enough.
It should be noted that 8 patients in this study had multiple myeloma cells with low levels of BCMA expression. Many people had previously worried that the response of these patients to the therapy may be problematic, but from the data published so far, all 8 patients were able to respond, and CR reached 38%. The final results of this study will be announced as early as next year.
It can be heard from the company’s name. Forty Seven is a company focused on the CD47 target. CD47 can be over-expressed on the surface of tumor cells, thus evading the surveillance of the immune system and the phagocytosis of macrophages. Inhibition of CD47 may make it easier for macrophages to engulf tumor cells.
At present, the company’s treatment for CD47 is divided into three directions: single-agent, combined therapeutic antibody drugs, and combined T-cell checkpoint inhibitors.
In patients receiving 5F9 monotherapy, the number of leukemia cells was reduced (39%) in 7 of 18 patients with relapsed AML in the bone marrow samples, and one of them had disease progression after 11.8 months of stable disease. Two of the 21 ovarian cancer patients and other solid tumor patients receiving 20 mg/kg or higher doses of 5F9 monotherapy responded.
The logic of 5F9 in combination with therapeutic antibody drugs is: by inhibiting the CD47 on the surface of tumor cells to inhibit the signal of “don’t eat me” by cancer cells, and labeling tumor cells with therapeutic antibodies, so that the tumor cells produce the “eat me” signal.
A few days ago Forty Seven announced on ASCO the data of 5F9 combined with rituximab in the treatment of non-Hodgkin’s lymphoma (n=22), with an ORR of 50% and a CR of 36%. The patients enrolled in the group experienced failures in over-the-counter drug treatment, so everyone’s response to these data was relatively positive.
Someone is happy that someone is jealous. If the above 4 are regarded as the big winners of this ASCO, then the following two companies are losers.
Nektar’s executives may not be very happy these past few days, because the clinical data of the company’s NKTR-214 announced at this year’s ASCO meeting has been questioned. If Nektar wanted to prove that the efficacy of NKTR-214 in combination with Opdivo was significantly better than Opdivo’s single drug at this year’s ASCO annual meeting, they obviously did not achieve this goal.
Early clinical data showed that 13 melanoma patients had a response rate of 85% after treatment. However, ORR decreased significantly after Nektar recruited 15 more patients into the group. In the data released at this year’s ASCO annual meeting, 14 of the 28 patients responded, which means that only 3 out of the 15 new recruits responded. It is also this data that makes the outside world seriously question the effectiveness of the combination therapy.
Nektar also published data on kidney cancer patients. The initial response rate of this group of patients was 64%, which means that 7 out of 11 patients responded. However, only 15 of the 15 additional kidney cancer patients enrolled had responded after the enrollment, resulting in a reduction in overall effectiveness of 46%.
Nektar and BMS explained that due to shorter treatment times, the response rate will increase further over time, but the current data show that it is unlikely that the previous ORR level will be reached.
Although the head of Nektar said that the efficacy of the combination therapy will increase the response rate over time. Perhaps Nektar/BMS is full of confidence in the future of drugs, but it is clear that investors do not buy it. Since this week, Nektar’s share price has fallen by 40%.
However, it is interesting to note that NKTR-214 is able to respond in PD-L1-negative patient populations, which are often difficult to respond to PD-1 inhibitors. Of the 12 PD-L1-negative melanoma patients, 5 responded. Of the 17 PD-L1 negative kidney cancer patients, 53% responded.
Many people are skeptical that BMS is too quick to take action against NKTR-214 in order to catch up with Merck. However, from the data released by this ASCO session, NKTR-214 may find it difficult to change the competitive landscape between Opdivo and Keytruda.
BMS/Nektar will conduct very expensive large-scale phase III clinical trials. It may be that the BMS chooses to place such a large bet on the NKTR-214/Opdivo joint venture plan will expose the company to high risks.
Opdivo is clearly the most important drug for BMS in recent years, but for the BMS, Merck’s Keytruda is a great threat. From the NKTR-214/Opdivo decision, we can also see the anxiety of BMS.
Jounce’s share price began to fall after the ASCO’s summary was made public and fell from about $17 on the previous month to approximately $7 today. The company’s JTX-2011 is an ICOS agonist, and Jounce believes that the ICOS agonism of JTX-2011 can activate CD4 T cells and inhibit Treg function.
JTX-2011 is currently in Phase I/II clinical (ICONIC). Phase I clinical part of ICONIC mainly studies PK and PD of JTX-2011, and phase II clinical research is mainly to study the extent of the drug’s infiltration of high expression of immune cells in ICOS. Higher efficacy in some types of tumors.
This year ASCO announced some of the data of ICONIC. JTX-2011 responded as a single agent to only one out of seven patients with gastric cancer, and 2 out of 19 patients responded with Opdivo with a response rate of 11%. Moreover, the data for the treatment of triple-negative breast cancer is equally ugly, and only one of the 15 triple-negative breast cancer patients has a partial response.
The person in charge of Jounce explained that the patients enrolled in the group were all patients who had previously been treated with multiple therapies, but were still unable to convince investors that the share price fell by nearly 30% after the summary was released.
Although there are many data on cancer immune combination therapy in this session of ASCO, it is still difficult to see how much potential the combination therapy can have, in addition to combined chemotherapy and combined use of Yervoy.
Nektar’s NKTR-214 related data is confusing. Jounce’s JTX-2011 has very low response rate for either single-agent or combined checkpoint inhibitors, and Dynavax’s TLR9 agonist SD-101 data is equally impressive. Disappointed. Furthermore, the IDO inhibitor data published in this ASCO was worse than expected, and the K-M curves of the two groups of patients almost coincided.
If this data is disappointing, a set of data that Nasima published in the abstract made me feel sad. Although Keytruda has already approved 10 indications, there is not much long-term follow-up data for this drug.
Merck submitted a summary to the ASCO meeting to publish five-year follow-up data on melanoma patients in KN001. After approximately five years, 412 patients were included in 655 enrolled patients, with a five-year survival rate of 34% and a median survival of 23.8 months.
Melanoma is considered to be a type of tumor with a high degree of response to immunotherapy, but the survival rate of patients with medication is still not high. Relatively speaking, high incidence of gastrointestinal cancer in the country is less responsive to the drug and can affect patients. It may also be relatively small. Keytruda is not a magic drug that many patients imagine, and immunotherapy still has a long way to go.