Roche, AstraZeneca, Moderna, Merck and Affimed presented new data in liver cancer, lung cancer, melanoma and lymphoma.
The 2023 American Association for Cancer Research (AACR) Annual Meeting kicked off over the weekend, featuring advances in the treatment of several cancer types.
Here are some notable presentations.
Roche’s Tecentriq-Avastin Combo in Adjuvant Liver Cancer
Interim results from Roche subsidiary Genentech’s Phase III IMbrave050 study showed the combination of Tecentriq (atezolizumab) and Avastin (bevacizumab) significantly improved recurrence-free survival (RFS) in adjuvant hepatocellular carcinoma (HCC), as compared with active surveillance.
IMbrave050 enrolled 668 patients who were deemed to be at a high risk of recurrence following surgery. After a median of 17.4 months, treatment with Genentech’s antibody combo reduced the risk of recurrence or death by 28%.
Overall survival data and those for other secondary endpoints were not yet mature at the time of the interim analysis, Pierce Chow, lead study author and senior consultant surgeon at the National Cancer Centre Singapore, said in a press interview.
There is a lack of proven and effective adjuvant treatments for HCC, Chow said, adding that patients who undergo resection or ablation typically have poor survival and often see their disease recur. Results from IMbrave050 help address this urgent need, he said.
According to a story from Fierce Pharma, there were 27 deaths in the Tecentriq-Avastin arm, two of which were directly attributed to the study treatment. Twenty patients in the active surveillance group died.
Serious adverse events occurred in 24.1% of patients treated with Tecentriq-Avastin, as opposed to 10.3% in active surveillance comparators.
The Tecentriq-Avastin combo is approved for use in HCC patients with unresectable or metastatic disease who have not previously received systemic therapy.
Moderna and Merck’s High-Risk Melanoma Combo
In the Phase IIb KEYNOTE-942/mRNA-4157-P201 trial, Moderna and Merck’s individualized mRNA vaccine combined with Merck’s Keytruda (pembrolizumab), a PD-1 blocker, boosted recurrence-free survival in patients with resected stage III/IV melanoma.
The mRNA vaccine, an individualized neoantigen therapy, works by priming the patient’s immune system to launch a potent anti-tumor response specific to their cancer’s mutation signature. Compared with Keytruda alone, the combination led to a 44% drop in the risk of recurrence or death. Over 12 months of observation, the RFS rate was 83.4%, which dropped slightly to 78.6% by 18 months.
In an exploratory subgroup analysis of patients with high and low tumor mutational burden, the use of the mRNA vaccine reduced the risk of recurrence or death by 35% and 41%, respectively.
As for safety, the observed adverse events were largely consistent with what had been previously recorded. Common toxicities included fatigue, injection-site pain and chills.
These data point to the potential of combining an individualized vaccine with PD-1 blockage in high-risk melanoma, Kyle Holen, senior vice president and head of development, therapeutics and oncology at Moderna, said in a statement. Moderna looks forward to beginning a Phase III trial soon, he said.
Beyond melanoma, the companies also plan to study this candidate in lung cancer, Holen said.
AstraZeneca’s Imfinzi in Late-Stage NSCLC
In a planned interim analysis of the Phase III AEGEAN study, AstraZeneca’s Imfinzi (durvalumab) plus neoadjuvant chemotherapy, followed by Imfinzi on its own, significantly improved event-free survival (EFS) in patients with early-stage non-small cell lung cancer (NSCLC), as compared with neoadjuvant chemotherapy alone.
The Imfinzi-based regimen cut the risk of recurrence, progression or death by 32%.
Pathologic complete response (pCR), defined as having no viable tumor after neoadjuvant treatment, was a key secondary endpoint of AEGEAN. The Imfinzi regimen led to a 17.2% pCR rate, as opposed to 4.3% after neoadjuvant chemotherapy alone.
AEGEAN’s results underline the importance of diagnosing NSCLC and initiating treatment earlier, when patients are most likely to be cured, Susan Galbraith, executive vice president of oncology R&D at AstraZeneca, said in a statement.
AstraZeneca will discuss these data with the regulatory bodies, Galbraith said.
The AEGEAN study consisted of 802 NSCLC patients who were given Imfinzi at a fixed dose of 1,500 mg. Those with tumor mutations in the EGFR and ALK genes were excluded from the study.
AEGEAN found no new safety signals in either the neoadjuvant or adjuvant settings.
Affimed’s Mid-Stage Lymphoma Study
Final data from the Phase II REDIRECT study showed that Affimed’s AFM13 was effective for the treatment of heavily pretreated, advanced relapsed or refractory peripheral T Cell Lymphoma (PTCL).
Affimed’s candidate induced a 32.4% objective response rate (ORR) and a 10.2% complete response rate (CRR) in the study’s intention-to-treat population. In the subgroup of patients with angioimmunoblastic T cell lymphoma, a common PTCL subtype, AFM13 elicited ORR and CRR values of 53.3% and 26.7%, respectively.
AFM13’s effects endured for a median of 2.3 months, and treated patients showed a median progression-free survival of 3.5 months. Overall survival was 13.8 months.
AFM13 is an investigational, first-in-class innate cell engager that works by activating innate immune players including natural killer cells and macrophages to attack CD30-positive hematologic cancer cells. It is Affimed’s most advanced innate cell engager.
REDIRECT is a multicenter, registration-directed trial enrolling 108 patients who received 200-mg intravenous infusions of AFM13.
Affimed reported an adverse event profile that was consistent with what had previously been reported. Common treatment-emergent toxicities included infusion-related reactions, neutropenia and pyrexia. There were no side effects that led to death.
Tristan Manalac is an independent science writer based in metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com
Clarification (April 18): This article has been updated to clarify that mRNA-4157/V94 is being jointly developed and commercialized by Merck and Moderna.
