Immuno-Oncology

Yvonne Chao, MD, PhD, discusses key trials leading to FDA approvals in metastatic non–small cell lung cancer.

Updated data from key trials in non–small cell lung cancer continue to demonstrate the superiority of immunotherapy and targeted therapy regimens for non–small cell lung cancer treatment, but the optimal use of these agents in the adjuvant vs neoadjuvant settings is still contested.

When the fully human IgG4 monoclonal antibody SRK-181 was given as a monotherapy or in combination with anti–PD-1 or PD-L1 agents in patients with locally advanced or metastatic solid tumors, it was found to be generally well tolerated and to demonstrate early indications of efficacy.

Although the immune system plays a vital role in attacking tumor cells, the immune mechanisms vary from tumor to tumor, and factors in the tumor microenvironment can reduce the effectiveness of the body’s immune response.

Given the current lack of positive phase 3 immunotherapy trials for glioblastoma, a misconception held by oncologists and neuro-oncologists is that immunotherapy has no place in this malignancy.

Durvalumab plus neoadjuvant chemotherapy followed by surgery and adjuvant single-agent durvalumab significantly improved event-free survival vs neoadjuvant chemotherapy and surgery alone in patients with resectable stage IIA-IIIB non–small cell lung cancer.

The addition of pembrolizumab to standard therapies failed to improve survival outcomes in patients with metastatic castration-resistant prostate cancer in the KEYNOTE-641 trial and patients with EGFR-mutated non–small cell lung cancer in the KEYNOTE-789 trial.

The FDA has provided PDS Biotechnology Corporation with guidance on the required contents of a design for a potential registrational trial examining PDS0101 in combination with PDS0301 and an FDA-approved immune checkpoint inhibitor in patients with recurrent or metastatic human papillomavirus–positive, ICI-refractory head and neck cancer.

The National Medical Products Administration of China has granted approval to tislelizumab in combination with fluoropyrimidine and platinum chemotherapy in the frontline treatment of patients with locally advanced unresectable or metastatic gastric or gastroesophageal junction adenocarcinoma with a high PD-L1 expression.

The combination of the targeted immunotherapy Bria-IMT and retifanlimab demonstrated signs of clinical benefit and was found to be well tolerated in patients with advanced metastatic breast cancer.

Pradnya D. Patil, MD, FACP, discusses unmet needs that remain to be addressed with the use of immunotherapy in patients with non–small cell lung cancer.

French investigators evaluated a potential solution to reduce myotoxicity and improve survival for patients with cancer receiving treatment with immune checkpoint inhibitors.

The FDA has granted a breakthrough therapy designation to the investigational personalized mRNA cancer vaccine mRNA-4157/V940 in combination with pembrolizumab for the adjuvant treatment of patients with high-risk melanoma following complete resection.

In this third episode of OncChats: Traveling Through the Lung Cancer Treatment Paradigm, Aaron Franke, MD, discusses the expanding role of neoadjuvant therapy in non–small cell lung cancer and efforts to better identify patients who can benefit from curative-intent treatment.

Checkpoint inhibitor–based salvage regimens significantly reduced the likelihood that patients with relapsed/refractory classic Hodgkin lymphoma undergoing transplant would need further salvage therapy vs conventional salvage regimens.

The combination of maveropepimut-S, pembrolizumab, and intermittent low-dose cyclophosphamide elicited responses in patients with relapsed or refractory diffuse large B-cell lymphoma, according to preliminary findings from the phase 2b VITALIZE trial.

Thomas J. George, MD, FACP, highlights the long-term data from the NRG-GI002 trial, the next steps for exploring subsets of patients who may benefit from the addition of pembrolizumab or veliparib to total neoadjuvant therapy, and what the use of total neoadjuvant therapy has meant for patients with stage II/III locally advanced rectal cancer.

James Harding, MD, highlighted current and emerging areas of research in biliary tract cancer, including key contributions from TOPAZ-1 and the phase 3 SWOG 1815 trial, the development of immunotherapy and chemotherapy combinations, and continued efforts to utilize personalized medicine in clinical practice.

The safety and efficacy of a combination regimen comprised of XL092 and atezolizumab is being compared with that of regorafenib monotherapy in patients with microsatellite stable or microsatellite instability–low metastatic colorectal cancer who have progressed on or are intolerant to standard-of-care therapy.

Ana Baramidze, MD, provides background on the FDA approvals of cemiplimab in NSCLC, expands on key efficacy and safety data with cemiplimab from EMPOWER-Lung 3, and discusses the current treatment landscape for patients with advanced NSCLC.

Neoadjuvant pembrolizumab was found to have high clinical activity and an acceptable safety profile in patients with localized microsatellite instability–high/deficient mismatch repair solid tumors.

Bavituximab in combination with pembrolizumab produced responses in patients with previously untreated advanced hepatocellular carcinoma.

Neoadjuvant treatment with anti–PD-1 inhibitors induced high rates of complete response and reduced recurrence rates, according to a retrospective analysis of patients with localized mismatch repair-deficient or microsatellite instability–high colorectal cancer.

A doublet comprised of the bispecific innate cell engager AFM24 and atezolizumab had a tolerable safety profile and elicited responses in patients with advanced EGFR-expressing solid tumors.

A triplet regimen comprised of COM701, BMS-986207, and nivolumab was found to have encouraging antitumor activity and favorable tolerability in patients with heavily pretreated, platinum-resistant ovarian cancer.

The utilization of the anti-CD40 agonist, CDX-1140, in combination with pembrolizumab was generally well tolerated and demonstrated preliminary efficacy in patients with anti–PD-1/PD-L1 resistant, locally advanced or metastatic solid tumors.

Treatment with adjuvant pembrolizumab resulted in favorable quality-of-life outcomes vs high-dose interferon α 2b or ipilimumab in patients with resected melanoma at high risk for relapse.

Neoadjuvant treatment with SHR-1701 with or without chemotherapy followed by surgery or radiotherapy induced responses in more than half of patients with stage III unresectable non–small cell lung cancer and increased resectability in those assigned to definitive surgery.

INT230-6 demonstrated direct tumor killing in soft tissue sarcoma and elicits an anti-cancer immune response within the injected tumor both alone and in combination with ipilimumab.

Treatment with INV-1120 was well tolerated and demonstrated preliminary signals of stable disease as a single agent in patients with advanced solid tumors.