ASCO24: Sanofi Reports Sarclisa Combo’s Fatality Reduction in Multiple Myeloma

Stay tuned to BioSpace as we keep you updated on all of the biggest data and news from the conference.

Pictured: Oncology tracker over the Chicago skyline/Nicole Bean for BioSpace

The American Society of Clinical Oncology (ASCO)’s annual meeting kicks off Friday in Chicago, with more than 5,000 abstracts highlighting investigational therapies for various malignancies. Analysts have expressed particular excitement for a new bispecific antibody, ADCs and a BCMA-targeted CAR-T cell therapy.

Stay tuned to BioSpace as we keep you updated on all of the biggest data and news from the conference.

Updated: June 4, 3:30 PM EST/2:30 PM CST

BMS’s Opdivo/Yervoy Combo Shows Promise in First-Line Against Liver Cancer

Bristol Myers Squibb announced on Tuesday that the Phase III data for a combination of its immunotherapy drugs Opdivo and Yervoy show a positive effect over two other medications in unresectable hepatocellular carcinoma (HCC), the most common type of liver cancer.

Results from the CheckMate-9DW trial reveal that the BMS combo had a median overall survival of 23.7 months versus 20.6 months for HCC patients on Eisai’s Lenvima or Bayer’s Nexavar. The objective response rate was 36% for the combination, and 13% for the Nexavar or Lenvima arm. BMS also posted a higher complete response rate of 7%, versus 2% for the other treatments. The median duration of response was 30.4 months in the combination arm and 12.9 for those on Nexavar or Lenvima.

“The combination of Opdivo plus Yervoy has been an established second-line treatment for patients with advanced HCC and, with these results, we can demonstrate that Opdivo plus Yervoy significantly increases survival and other key efficacy measures in the first-line setting for patients with advanced disease,” said Dana Walker, BMS’ vice president, global program lead, gastrointestinal and genitourinary cancers, in a statement.

BMS noted that the safety profile for the combo has “remained consistent” with previous data. At the same time, treatment-related adverse events were reported in 84% of the combination group and 91% of the patients receiving Nexavar or Lenvima.

Fierce Pharma noted that the combination may be competing with several others, including Roche’s Tencentriq and Avastin and AstraZeneca’s Imjudo and Imfinzi. Both of those combinations are approved for liver cancer.

Sanofi Reports Sarclisa Combo’s Fatality Reduction in Multiple Myeloma

Sanofi announced on Monday at the ASCO annual meeting that a combination treatment that includes its anti-CD38 monoclonal antibody Sarclisa had shown a positive effect in reducing disease progression and death in multiple myeloma patients. The news comes as Sanofi pushes for another indication for the drug.

The trial investigated Sarclisa in combination with the cancer treatments bortezomib, lenalidomide and dexamethasone (VRd), the standard of care in patients with newly diagnosed multiple myeloma who are not eligible for transplant. The combination reduced the risk of death or disease progression by 40% compared to VRd (p=0.0005). At a median follow-up of 59.7 months, the median progression-free survival (PFS) in the Sarclisa-VRd combo was not reached versus 54.3 months in the standard of care arm. The estimated PFS at 60 months was 63.2% for those treated with the combo versus 45.2% for those on the standard of care.

Sanofi also noted that in the secondary endpoints, 74.7% of patients in the combo arm had a complete response (CR) compared to 64% of those on the standard of care, while 55.5% of patients treated with the combination achieved minimal residual disease (MRD)-negative CR compared to 40.9% in the standard-of-care group. MRD was sustained for 12 months for 46.8% of patients in the Sarclisa combo arm compared to 24.3% on the standard of care. At the date of the data’s cutoff, 47.2% of patients on the combo remained on treatment compared to 24.3% on VRd.

Sanofi did note that no regulatory body had thoroughly evaluated the use of Sarclisa in combination with VRd in transplant-ineligible patients. However, the FDA has accepted the supplemental biologics license application for the investigational side of the combo while a regulatory submission is underway in the EU. The drug is already approved in multiple countries in combination with other drugs to treat patients with relapsed refractory multiple myeloma whose disease has progressed on other therapies.

BMS’ Breyanzi Shows Clinical Effect at Three Years in Large B-Cell Lymphoma

Bristol Myers Squibb’s CAR-T cell therapy Breyanzi has displayed further efficacy after nearly three years of follow-up, the company announced at the ASCO annual meeting on Monday.

According to BMS, the Phase III TRANSFORM trial investigated the therapy as a second-line treatment for patients with relapsed or refractory large B-cell lymphoma (LBCL). At a median follow-up of 33.9 months, Breyanzi had “sustained clinical benefit” with “continued improvements” in the primary endpoint of event-free survival (EFS). The EFS of Breyanzi patients was 29.5 months compared to just 2.4 months for patients taking the standard of care. The 36-month EFS rate with the CAR-T cell therapy was 48.5% versus 19.1% with the standard of care.

For the secondary endpoints, the overall response rate (ORR) was 87% for Breyanzi, while 74% of patients achieved a complete response (CR) with the treatment. Those on the standard of care had an ORR of 49% and a CR rate of 43%. The duration of response was not reached with Breyanzi and was 9.1 months with the standard of care. The 36-month progression-free survival (PFS) rate for Breyanzi was 50.9% versus 26.5% percent in the control group.

No new safety signals for the treatment were identified.

BMS’s Opdivo Displays Encouraging Results in Early and Advanced NSCLC

At the ASCO annual meeting on Monday, Bristol Myers Squibb provided three updates on its immunotherapy Opdivo and Opdivo-based combinations in treating non-small cell lung cancer (NSCLC).

First, the CheckMate-77T trial evaluated a regimen of neoadjuvant Opdivo with chemotherapy followed by surgery and adjuvant Opdivo in patients with stage III resectable NSCLC. The Opdivo regimen was compared to neoadjuvant chemo and placebo followed by surgery and adjuvant placebo. The perioperative Opdivo regimen had improved median event-free survival (EFS) regardless of nodal status, and one-year EFS rates were also higher in the Opdivo group. According to BMS, the data from this group was used to support regulatory filings for both the FDA and the European Medicines Agency for resectable NSCLC back in February.

The company also presented four-year data Sunday for its Phase III CheckMate-816 trial, which evaluated Opdivo with chemotherapy as a treatment in stage IB-IIIA resectable NSCLC. At 57.6 months, the Opdivo plus chemo group had improved EFS versus chemotherapy alone, with a median of 43.8 months versus 18.4 months. Four-year EFS rates were also higher in the Opdivo arm at 49% vs 38%. However, the difference in overall survival (OS) was not statistically significant between the groups and will continue to be followed, according to BMS. The company noted that 71% of patients treated in the Opdivo arm were alive after four years, compared to 58% in the Chemo arm.

BMS also provided a five-year update to the Phase III CheckMate-9LA trial, which investigated a combination of Opdivo plus Yervoy with two cycles of chemo versus chemo alone in the first line in metastatic NSCLC. At a 57.3-month minimum follow-up, the combination therapy had improved overall survival, with 18% of patients treated with the combo alive after five years compared to 11% in the chemo arm. Also, the responses were “more durable” in the combination, with 19% of patients still in response compared to 8% in the chemo group.

Merck/Moderna Cancer Combo Shows Benefit at Three-Year Mark

A combination of Merck and Moderna’s co-developed cancer vaccine, mRNA-4157, and Merck’s blockbuster cancer treatment Keytruda has continued to show clinical effects after three years and reached the primary endpoint in its latest trial, building on the earlier analysis of the primary and key secondary endpoints of the study, presented in 2023.

The combination was evaluated in a Phase IIb trial in patients with resected high-risk melanoma following complete resection. The median follow-up of three years showed that the combo continued to show a clinically meaningful and durable improvement in the primary endpoint of recurrence-free survival (RFS), and reduced the risk of recurrence or death by 49% compared to Keytruda alone. For the secondary endpoint of distant metastasis-free survival (DMFS), the risk of developing distant metastasis or death was reduced by 62% compared to Keytruda alone.

The data will be presented on Monday at the 2024 ASCO annual meeting, but there is also a plan to have another year of follow-up.

The combo’s safety profile was “consistent” with the primary analysis, according to the companies’ announcement. The most common events were fatigue, injection site pain and chills, with most adverse events being grade one or two. Moderna and Merck are now “actively enrolling” Phase III trials for the combo in high-risk melanoma and non-small cell lung cancer.

“These data highlight the sustained benefit in RFS and DMFS of mRNA-4157 (V940) as adjuvant treatment in combination with Keytruda in people with resected high-risk melanoma. Importantly, this benefit was observed across various patient exploratory subgroups, reflecting the potential of mRNA-4157 (V940) for a broad range of these patients,” Kyle Holen, Moderna’s senior vice president and head of development for therapeutics and oncology, said in a statement.

AstraZeneca and Daiichi Sankyo’s Enhertu Scores Positive Results in Breast Cancer

Daiichi Sankyo and AstraZeneca announced on Sunday that their antibody-drug conjugate (ADC) Enhertu displayed a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus chemotherapy in breast cancer.

The Destiny-Breast06 Phase III trial was conducted in patients with HR-positive, HER2-low and HER2-ultralow breast cancer whose disease can progressed despite one or more lines of endocrine therapy. The trial results showed that for patients with HER2-low breast cancer, Enhertu reduced disease progression or death by 38% versus chemotherapy with a p-value of p<0.0001. The median PFS rate was 13.2 months in the ADC arm versus 8.1 months with chemotherapy. For the overall trial population, the ADC reduced the risk of disease progression or death by 37% reduction versus chemotherapy and also had a 13.2-month PFS with a p-value of p<0.0001.

In the overall population, the objective response rate (ORR) was 57.3% for Enhertu and 31.2% for chemotherapy. Complete responses were identified in 13 patients on Enhertu, including nine with HER2-low expression and four patients in the ultralow subpopulation. No complete responses were found in the chemo arm.

“DESTINY-Breast06 represents another potential paradigm shift in how we treat patients across the spectrum of HR-positive metastatic breast cancer,” Susan Galbraith, executive vice president for oncology R&D at AstraZeneca, said in a statement. “The results reinforce the potential for Enhertu to improve outcomes earlier in the treatment landscape and in a broader population of patients with HER2-expressing breast cancer who have never before been eligible for a HER2-directed therapy.”

GSK’s Blenrep Slows Disease Progression in Late-Stage Trial

GSK announced on Sunday at the ASCO Annual Meeting that its antibody-drug conjugate (ADC) Blenrep has shown positive results in multiple myeloma—despite being off the U.S. market.

According to GSK, the Phase III Dreamm-8 trial reached its primary endpoint of progression-free survival (PFS). The trial investigated Blenrep in combination with pomalidomide and dexamethasone (PomDex) against the standard of care, bortezomib and PomDex, as a second-line and later treatment for relapsed or refractory multiple myeloma.

The PFS showed clinically meaningful improvement that was statistically significant, GSK said, with a p-value of <0.001. At the end of one year, 71% of patients on the Blenrep combination were alive and had not experienced disease progression, compared to 51% of those on the standard of care.

For overall survival (OS), GSK said it observed a “positive” trend but this difference was not statistically significant at the interim analysis, and further study of this metric is planned. At the end of one year, 83% of patients in the Blenrep arm were alive versus 76% on the standard of care.

GSK added that the experimental combo’s benefit was observed across all of the pre-specified subgroups, including those with “poor prognostic features.”

“With the robust results from the DREAMM-8 phase III head-to-head trial, we now have consistent data from two phase III trials supporting the potential for Blenrep combinations to redefine the treatment of multiple myeloma at or after first relapse,” Hesham Abdullah, senior vice president and global head of oncology R&D at GSK, said in a statement.

In 2022, Blenrep was withdrawn from the U.S. market at the FDA’s request after failing a Phase III confirmatory study.

Imfinzi Late-Stage Trial Displays a 27% Reduction in Death

AstraZeneca’s PD-L1 blocker Imfinzi reached the co-primary endpoints of progression-free survival (PFS) and overall survival (OS) in a Phase III trial for limited-stage small cell lung cancer (LS-SCLC), the company announced on Sunday.

The interim results from the Phase III Adriatic trial, which compared Imfinzi to a placebo, showed that the drug had reduced the risk of death by 27%. The approximated median OS was 55.9 months for the Imfinzi group versus 33.4 months for the placebo arm. AstraZeneca also noted that 57% of patients treated with Imfinzi were alive at three years compared to 48% on the placebo. Imfinzi also reduced the risk of disease progression or death by 24%, with a median PFS of 16.6 months for patients on the drug versus 9.2 months for those on the placebo. Around 46% of participants on the drug also did not experience disease progression after two years compared to 34% on the placebo.

“The strong improvement in overall survival seen with Imfinzi after concurrent chemoradiotherapy is transformative in the treatment of limited-stage small cell lung cancer,” Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said in a statement.

Imfinzi’s safety profile was “generally manageable,” and no new safety signals were found. However, 24.4% of patients on the drug and 24.2% on placebo had grade three and four adverse events.

Takeda and Pfizer’s Hodgkin Lymphoma Combo Improves Survival

On Saturday, Pfizer and Takeda posted positive results for a combination of the antibody-drug conjugate Adcetris in Hodgkin’s lymphoma.

According to Pfizer and Takeda, which has the commercialization rights to Adcetris outside of the U.S. and Canada, the Phase III HD21 study evaluated the ADC in combination with several other cancer treatments such as etoposide, cyclophosphamide, doxorubicin, dacarbazine and dexamethasone (BrECADD). The combination was pitted against the standard of care, a cocktail of seven cancer drugs, in newly diagnosed Stage IIb/III/IV classical Hodgkin’s lymphoma patients. The three-year analysis found that the experimental combination had met the co-primary endpoints, displaying improved safety and “non-inferior” progression-free survival (PFS).

After 48 months, the ADC combination has shown a “superior efficacy” to the standard of care, netting 94.3% in PFS versus 90.9% with a p-value of p<0.035. Treatment-related morbidity was also lower than the standard of care at 42% versus 59% (p<0.001). The study also found that the Adcetris combo had an improved risk-to-benefit profile compared to the current standard.

“We initiated the HD21 trial with the hope of improving outcomes currently being achieved by a standard of care, as many patients with newly diagnosed disease often experience a high treatment burden,” Peter Borchmann of the University Hospital of Cologne, Germany, and trial chairman of the HD21 study said in a statement. “The presented analysis, in which the ADCETRIS regimen demonstrates superior progression-free survival, as well as a tolerable safety profile, reveals the meaningful potential this ADCETRIS + ECADD regimen has to offer these patients.”

Pfizer has also presented encouraging results for its ALK- inhibitor Lorbrena at ASCO.

BMS’s Krazati Reaches Primary Endpoint in NSCLC

Bristol Myers Squibb announced on Saturday at the American Society of Clinical Oncology (ASCO) annual meeting that the small-molecule KRASG12C inhibitor Krazati had reached its primary endpoint in a Phase III trial in non-small cell lung cancer (NSCLC).

According to BMS, the Phase III Krystal-12 trial pitted Krazati against chemotherapy in patients with locally advanced or metastatic KRASG12C-mutated NSCLC who have already received docetaxel. The results showed that the treatment induced a statistically significant and clinically meaningful improvement in progression-free survival (PFS) at a median follow-up of 9.4 months. The median PFS was 5.5 months for Krazati, compared to 3.8 in the chemotherapy arm. The overall response rate (ORR) was also higher in Krazati versus docetaxel, with a p-value of p<0.0001. The median duration of response was 8.31 months in Krazati patients versus 5.36 months in the chemo arm.

Krazati also had an intracranial response among patients with central nervous system metastases and displayed a response rate that was more than double that of docetaxel. BMS said that the study is ongoing and will assess the secondary endpoint of overall survival.

“These confirmatory results further support KRAZATI as an efficacious, targeted treatment option for these patients,” Abderrahim Oukessou, vice president and global program lead for KRAZATI at BMS, said in a statement. “We look forward to further sharing these results while also continuing to evaluate KRAZATI in other advanced KRASG12C-mutated solid tumors.”

Krazati came into BMS’s possession late last year when it acquired Mirati Therapeutics for $4.8 billion.

Pfizer Reveals Positive Data for Lorbrena

Pfizer announced on Friday that results from its Phase III trial evaluating its ALK inhibitor Lorbrena had shown extensive progression-free survival (PFS) improvement in non-small cell lung cancer (NSCLC) patients.

The trial pitted Lorbrena against Pfizer’s other NSCLC treatment, Xalkori, in patients with untreated, anaplastic ALK-positive NSCLC. The results showed that 60% of patients treated with Lorbrena were alive after five years without disease progression compared to just 8% in the Xalkori arm. Also, after five years of median follow-up, the median PFS based on investigator assessment was not reached with Lorbrena and had a hazard ratio of 0.19. According to Pfizer, this represents an 81% reduction in the rate of disease progression or death compared to Xalkori.

“These results from the CROWN trial are unprecedented, as the majority of patients on Lorbrena are living beyond five years without disease progression,” Roger Dansey, chief development officer, oncology at Pfizer, said in a statement.

Lorbrena also showed a 94% reduction in the risk of developing intracranial progression (IC), with the median time to IC progression not being reached. In contrast, the Xalkori group reached it in 16.4 months. No new safety issues with Lorbrena were discovered.

According to Reuters, Pfizer now expects Lorbrena’s annual sales to hit $1 billion by 2030. The drug has brought in a total of $164 million in Q1 2024, a 46% increase from Q1 2023.

Novartis’ Leukemia Drug Prevails Over Older Therapies in Phase III

Novartis’ kinase inhibitor Scemblix aced a Phase III trial in chronic myeloid leukemia (CML), the pharma reported at ASCO on Friday.

In the ASC4FIRST trial, where Scemblix was pitted against current standard-of-care tyrosine kinase inhibitor (TKI) therapies, Novartis’ drug elicited a major molecular response in 68% of patients compared to 49% in the TKI arm. A deep molecular response, which is often considered a remission in chronic myeloid leukemia, was seen in 39% of patients treated with Scemblix versus 21% in the comparison arms, one of which was Novartis’ Gleevec.

Scemblix was designed to elicit high potency and high specificity in order to minimize side effects and toxicities—an effect that was also born out in the trial, where 86% of patients on Scemblix remained on the treatment at the cutoff date compared to only 62% of patients on Gleevec and 75% on a second generation TKI.

Gilead Shares Details on Failed Trodelvy NSCLC Trial

In January, Gilead Sciences announced that its antibody-drug conjugate, Trodelvy, missed the primary endpoint of overall survival in non-small cell lung cancer (NSCLC). On Friday at ASCO, the company revealed more details. In the EVOKE-01 trial, the ADC showed a 16% reduction in the risk of death compared with the chemotherapy docetaxel, while the median survival benefit was just 1.3 months for those treated with Trodelvy, Endpoints News reported. However, the OS margin was greater for those patients whose tumors did not respond to their last anti-PD(L)1-containing treatment, at 11.8 months for Trodelvy and 8.3 months for docetaxel.

Trodelvy’s safety profile was also superior to docetaxel, Endpoints reported, with fewer grade 3 or worse adverse events and fewer discontinuations from toxicities compared with chemotherapy.

“These data, including the meaningful benefit observed in the sub-group of patients, are encouraging and warrants further investigation as these patients have a great unmet need,” Luis Paz-Ares, head of medical oncology service at Hospital Universitario 12 de Octubre in Madrid, said in a press release, according to Endpoints.

Deaths, Safety Issues Plague J&J’s Prostate Cancer Trial

Four deaths were reported in a Phase I study of Johnson and Johnson’s radiopharmaceutical candidate JNJ-6420, investigating the candidate’s use in metastatic castration-resistant prostate cancer. Two of the deaths were from interstitial lung disease (ILD) and two were due to COVID and “failure to thrive.”

According to the readout, posted ahead of the American Society of Clinical Oncology annual meeting, 32% of evaluable patients experienced a serious treatment-emergent adverse event (TEAE) but only half of those were attributed to JNJ-69086420 (16%), while 61% experienced a Grade 3 or higher TEAE but only 45% experienced a Grade 3 or higher AE attributed to JNJ-6420. These adverse events included thrombocytopenia and interstitial lung disease, but were mitigated with a cumulative dose cap and an adaptive dosing schedule. As is made clear in the ASCO presentation, there have been no further ILD cases of any grade after implementation of a cumulative dose cap.

According to the updated data that was presented at ASCO on the 36 patients in the 250µCi dose cohort, there was a 44% PSA50 response rate among 32 evaluable patients. For 17 evaluable patients, there was an 18% ORR. JNJ-6420, an α-selective radioligand therapy that is the first to target hK2, elicited deep and durable biochemical responses in patients with mCRPC.

At the 250 μCi dose level (n = 36), 44% confirmed PSA50, 9% confirmed PSA90, and 18% RECIST ORR (1 CR, 2 PR; n/N=3/17). According to the presentation, one to two doses JNJ-6420 led to “profound and durable biochemical and radiographic responses.”

Nimbus’ HPK1 Inhibitor Shows Positive Early-Stage Results

Boston-based Nimbus Therapeutics’ oral small-molecule hematopoietic progenitor kinase 1 (HPK1) inhibitor, NDI-101150, displayed positive early results in a Phase I/II study.

Five out of 30 evaluable patients, or 16.7%, had some clinical benefit after treatment with the candidate, with one patient with renal cell carcinoma (RCC) netting a complete response and another patient seeing a partial response. Three patients with RCC, pancreatic and endometrial cancer separately maintained durable, stable disease for more than six months while on treatment.

Nimbus chief medical officer Nathalie Franchimont said the company is “encouraged” by the results, which will be presented at the annual American Society of Clinical Oncology (ASCO)conference.

“HPK1 inhibition is a promising therapeutic approach as it is shown to activate T cells, B cells and dendritic cells to mount a robust anti-tumor response, whereas currently approved checkpoint inhibitors activate T cells,” Franchimont said in a statement.

Regeneron Bispecific Antibody Has Underwhelming Showing

Regeneron Pharmaceuticals unveiled early data last week showing its bispecific antibody REGN7075, in combination with Libtayo, treating microsatellite-stable colorectal cancer (MSS CRC). According to the company, among the 94 patients treated in the dose escalation trial as of the data cutoff, there was an overall response rate of only 6%. One patient had a complete response, while two others had a partial response and 12 patients were reported to have stable disease.

The responders were found to lack liver metastases, and for the subset of 15 patients without liver metastases, there was a 20% overall response rate and an 80% disease control rate.

Israel Lowy, Regeneron’s senior vice president for translational and clinical oncology, said the early data “speak to the potential of REGN7075 in combination with Libtayo and add to a growing body of evidence supporting novel costimulatory bispecifics that are in clinical trials for a range of solid tumors and blood cancers.”

Regeneron plans to unveil the trial’s details at the American Society of Clinical Oncology(ASCO) 2024 Annual Meeting in Chicago.