The swath of agents and regimens approved for the first-line treatment of patients with advanced melanoma has muddied second-line treatment decision-making for this patient population, according to Justin Moser, MD, who added that past and ongoing clinical trials investigating immunotherapy strategies beyond checkpoint inhibition could help refine treatment strategies in this setting.

One agent currently indicated in the second-line space is lifileucel (Amtagvi), 

which received accelerated approval from the FDA

 in February 2024 for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 antibody, and if 

 V600 positive, a BRAF inhibitor with or without a MEK inhibitor.

As mounting evidence suggests limited benefit from additional checkpoint blockade in patients previously unresponsive to dual checkpoint inhibition, concentrated efforts to diversify immunotherapy strategies via tumor-infiltrating lymphocyte (TIL) therapies such as lifileucel, T-cell receptor therapies, intratumoral agents, and cytokine-based approaches are gaining traction, Moser said.

“It is exciting that [the field] is beginning to move away from [the development of] novel checkpoint inhibitors,” Moser stated in an interview with 

. “We’re starting to approach treatment-refractory melanoma [management] similarly to other tumor types such as ovarian cancer, where treatment decisions are informed by the [duration of response] or benefit [with prior therapy].”

In the interview, Moser discussed the limitations of current PD-1–based regimens for patients with primary or secondary resistance; the role of lifileucel in addressing unmet needs in advanced melanoma and factors influencing patient selection for this TIL therapy; and the ongoing exploration of alternative mechanisms of action to target during drug development for checkpoint-refractory disease.

Moser is a medical oncologist at HonorHealth and associate clinical investigator at HonorHealth Research Institute in Scottsdale, Arizona.

: What are some of the current advantages and limitations of anti–PD-1–based therapies in metastatic melanoma?

Immune checkpoint inhibitors—particularly PD-1–based treatments—have revolutionized the care of patients with melanoma. Prior to checkpoint inhibitors, the median survival for [advanced] melanoma was less than 6 months. Now, based on recent data, it is well over 7.5 years. It is clear that some patients are benefiting [from checkpoint inhibitors]. However, the patients who do not benefit from these therapies [represent] a significant unmet need.

What factors inform treatment decision-making for patients with advanced melanoma who respond poorly to, or are ineligible for, standard checkpoint inhibitor–based regimens?

When we look at people who initially progress on a combination of checkpoint inhibitors—whether [it be] nivolumab [Opdivo] plus ipilimumab [Yervoy] or nivolumab plus relatlimab-rmbw [Opdualag]—if those patients do not have a 

 mutation, the most readily available treatment options are other checkpoint inhibitor combinations. How appropriate of an option that is depends on how well [patients] did on the initial combination. One of the challenges in melanoma is that the vast majority of the FDA-approved treatments that remain clinically relevant today are approved in the frontline setting. This means there is limited data to guide treatment in the second-line setting—without a clear frontline standard, there is also no standard for second-line treatment—making it difficult to determine the optimal next step.

Based on retrospective data, the likelihood of benefiting from a second-line checkpoint inhibitor–based combination appears to depend on the response to initial treatment. For people who initially respond to nivolumab plus relatlimab or nivolumab plus ipilimumab and then develop secondary resistance, there is an approximately 30% to 33% chance of responding to the other combination. When a patient presents with disease progression on a combination regimen, the first consideration is how they responded to the initial therapy, as this helps determine whether switching combinations is a reasonable approach.

For those who had no initial benefit from combination checkpoint inhibitors, the chance of responding to another checkpoint combination is likely 10% or less. In those cases, non–checkpoint inhibitor–based strategies are pursued, as these patients are likely resistant to checkpoint blockade and require therapies with a different mechanism of action.

How has the FDA approval of lifileucel affected the real-world treatment of patients with advanced melanoma who have progressed on prior immune checkpoint inhibitors?

[Lifileucel] has been slow to impact clinical practice. Lifileucel is a very intense therapy that requires involvement from multiple care team members and a multidisciplinary infrastructure. Although its adoption has increased, there was an initial delay in opening treatment centers. We have been operational since approximately April [2024] and have started using this therapy primarily for patients with primary resistance or those who have developed resistance to combination checkpoint inhibitors.

In the single-arm [phase 2 C-144-01] study [NCT02360579] that led to its approval, lifileucel demonstrated an objective response rate of 31.5% [95% CI, 21.1%-43.4%], with nearly half of responders experiencing durable responses lasting over 2 years. As is typical when a new treatment is approved in oncology, initial use often occurs in the sickest patients who have been awaiting new options the longest. Consequently, real-world outcomes may not immediately reflect the results seen in clinical trials. Over time, as lifileucel is administered earlier and in more appropriate clinical contexts, outcomes may improve.

Trial data have also indicated that patients with lower disease burden, [those being treated in] earlier lines of therapy, and [patients with] normal or lower lactate dehydrogenase [LDH] levels were more likely to benefit. Although not all patients respond [to this therapy, which is] consistent with all available cancer therapies, we have seen clinical benefit in patients previously treated with PD-1–based therapies, including some who had progressed on 3 to 5 prior lines of therapy.

What factors do you consider when determining if a patient is a candidate for lifileucel?

Not everyone is a candidate for lifileucel therapy. On average, approximately half of the patients referred for lifileucel are deemed ineligible, due to various factors. To generate the TIL product, a minimum [diameter] of 1.5 cm of tumor must be resected, meaning the tumor must be of sufficient size. With the FDA approval, the required number of cells for product generation increased, and product specifications were tightened. [In some cases], 2 to 3 cm of tumor may be required, and not all patients have resectable lesions of that size or lesions located in areas that can be safely excised.

Beyond tumor accessibility, patients must also be physically fit for therapy. Lifileucel requires lymphodepleting chemotherapy, which is more intensive than regimens used in CAR T-cell or T-cell receptor therapies. Patients must be candidates for both high-dose cytotoxic chemotherapy and high-dose interleukin-2 [IL-2]. Pre-treatment evaluation includes echocardiography to ensure adequate ejection fraction, pulmonary function testing, and performance status assessments.

However, patients who meet these objective criteria may still be unsuitable. In clinical experience, individuals over 70 years of age generally do not tolerate TIL therapy well. Thus, [we need to be] cautious with patient selection [for those over 70 years]. Functional status is another key determinant. Patients who are unable to walk a mile or climb a flight of stairs are not offered therapy until they can demonstrate the physical capacity to walk multiple miles continuously or ascend stairs. Optimal baseline fitness is essential to both tolerate therapy and recover post-treatment.

Has longer-term follow-up from the C-144-01 trial improved the identification of patients who may derive benefit from this TIL therapy? Could additional follow-up help further improve patient selection?

[Longer-term follow-up has highlighted some] of the same markers seen in the initial study—patients with lower-volume disease and normal LDH levels were more likely to benefit. This could be due to several reasons. Normal LDH and low disease burden are established predictors of response to various therapies in melanoma. Patients with these characteristics are more likely to respond to BRAF and MEK inhibitors if they have a 

 mutation, as well as to checkpoint inhibitors.

These markers may be particularly important for TIL therapy. During surgery, the TILs harvested are specific to the tumor sample obtained. These T cells are expanded ex vivo and then reinfused. In patients with multifocal disease or high tumor burden, it is often not feasible to biopsy or resect every lesion. Although efforts are made to collect tissue from multiple sites, sampling is inherently limited—performing 20 lung biopsies or wedge resections is not practical.

As tumor burden increases, intratumoral heterogeneity also tends to increase. This presents a potential limitation for TIL therapy, as the infused lymphocytes may only recognize antigens expressed by the resected tumor site, but not by other lesions. This can result in mixed responses or partial responses, particularly in patients with more advanced or heterogeneous disease.

Are there any other ongoing clinical trials that could move the needle forward for patients with metastatic melanoma in the post–PD-1 inhibition setting?

We have a lot of phase 2 trials that have been completed or are ongoing in melanoma. RP1, an oncolytic injectable virus, is currently

 [in combination with nivolumab, and has] a Prescription Drug User Fee Act date set for July [22, 2025]. [RP1] is a genetically modified virus similar to talimogene laherparepvec [T-VEC; Imlygic], but data [suggest] that it may offer improved efficacy and [has more] clinical advantages. [RP1 can be] administered at higher volumes, allowing greater tumor coverage, and it can be injected into deep lesions using CT-guided [imaging]. Although T-VEC has demonstrated efficacy in a select group of patients with melanoma, including some durable complete responses, its use has been limited by practical constraints. RP1 may broaden the population eligible for intratumoral viral therapy.

Additionally, the randomized phase 3 [SUPRAME trial (NCT06743126)] is evaluating a novel T-cell receptor therapy for melanoma. Genetically, engineered T-cell receptor therapies may offer enhanced potency compared with TIL therapy. [Unlike TIL, T-cell receptor] therapy does not require high-dose IL-2, which is responsible for much of the toxicity associated with TIL-based approaches, and TCR therapy can be administered with lower doses of chemotherapy. [However], the restriction with T-cell receptor therapy is that [patients] must be HLA-matched, limiting its applicability. [Still], phase 1 data showed a response rate of over 50% among patients with refractory melanoma.

Lastly, the ongoing randomized phase 3 [TEBE-AM trial (NCT05549297)] of tebentafusp-tebn [Kimmtrak] is investigating this agent in patients with refractory melanoma. Tebentafusp is also HLA-A*02:01–restricted, targeting a similar patient population. Phase 1b expansion data showed that tebentafusp may be effective in patients with melanoma who are refractory to dual immune checkpoint inhibition. For this patient population, rechallenge with checkpoint inhibitors is unlikely be beneficial, [highlighting] the need for therapies with novel mechanisms of action such as tebentafusp, T-cell receptor therapy, and RP1.

How do you see the post–PD-1 melanoma space continuing to evolve with additional research?

Although immune checkpoint inhibitors have revolutionized the field, we’re learning that [patients who are] dual checkpoint inhibitor–refractory are unlikely to benefit from further checkpoint inhibitor–based therapies. [A patient with melanoma] who responded to dual checkpoint inhibition for [at least] 6 months may reasonably be considered for another immunotherapy approach. However, for patients who received PD-1–based therapy and did not derive any meaningful benefit, we need new options and non–checkpoint inhibitor–based therapies.

[Although] later-stage therapies such as tebentafusp, [T-cell receptor] therapy, and RP1 are promising in this space, the early-phase pipeline is also active. [For example], cytokine-based therapies are another immunotherapy that do not overlap with checkpoint inhibitors. Novel delivery platforms—including prodrugs, intratumorally activated agents, and ‘immunokines’—are also being explored. In the next couple of years, we’re going to see some exciting data read out with these novel cytokines as well, which will just add another tool to our repertoire.

FDA approves first cellular therapy to treat patients with unresectable or metastatic melanoma. News release. FDA. February 16, 2024. Accessed February 16, 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-cellular-therapy-treat-patients-unresectable-or-metastatic-melanoma

Articles

Justin Moser, MD, discusses efforts to develop a broader range of immunotherapy approaches for advanced melanoma after PD-1 inhibition.

Lifileucel Paves the Way for Evolving Treatment Approaches After PD-1 Inhibition in Advanced Melanoma

Dr Moser on Treatment Considerations After Progression on Frontline PD-1 Inhibitors in Melanoma

"One of the challenges we have in melanoma is that the vast majority…of FDA-approved treatments that are still clinically relevant today are approved in the frontline setting. [Therefore, it’s hard to know what the best option is for [a patient in the] second-line. [However], based on retrospective data, it looks like the chance of [a patient] benefiting from a second-line checkpoint inhibitor–based combination depends on how well they responded in the first line."

Justin Moser, MD, a medical oncologist at HonorHealth and an associate clinical investigator at HonorHealth Research Institute, discussed therapeutic decision-making for patients with advanced melanoma who progress following initial treatment with checkpoint inhibitor–based combinations, such as nivolumab (Opdivo) plus ipilimumab (Yervoy) or nivolumab plus relatlimab-rmbw (Opdualag).

A major clinical challenge in this setting is that most FDA-approved regimens are indicated in the frontline setting, leaving limited guidance or prospective data to inform second-line strategies, Moser began. For patients without a 

 mutation, the most accessible second-line options remain other checkpoint inhibitor combinations, Moser stated. However, the utility of these regimens is highly dependent on the patient’s initial response to immunotherapy, Moser stated.

Retrospective data suggest that patients who achieve a clinical benefit—such as partial response, complete response, or prolonged disease stability—before developing resistance to first-line checkpoint blockade have an approximately 30% to 33% chance of responding to a different checkpoint combination in the second-line setting, Moser stated. In these cases, re-challenging with another immunotherapy combination may be reasonable, particularly if the initial benefit was durable, Moser stated.

In contrast, for patients with primary resistance to frontline checkpoint inhibition—defined as no clinical benefit or early progression—the likelihood of response to a subsequent immunotherapy-based approach is low, likely under 10%, Moser stated. For these patients, non–checkpoint inhibitor–based strategies may be more appropriate, including clinical trial enrollment or other agents with alternative mechanisms of action, Moser stated.

Evaluating how a patient responded to their initial therapy is essential when determining appropriate next steps, Moser stated. He emphasized the need for prospective studies to better guide post–checkpoint inhibitor treatment, particularly for patients without actionable mutations, and underscored the importance of ongoing research to address resistance and expand second-line options for this population.

Although checkpoint inhibitors have transformed melanoma treatment, patients with dual checkpoint inhibitor–refractory disease are unlikely to benefit from additional checkpoint-based therapies, Moser stated. If patients responded to a prior checkpoint inhibitor and maintained benefit, re-challenge may be reasonable; otherwise, alternative strategies are needed, Moser asserted. Novel immune approaches, including cell therapies like tumor-infiltrating lymphocytes and investigational cytokines with improved delivery mechanisms, are showing early promise in phase 1 trials and may soon expand available options, Moser concluded.

Videos

Justin Moser, MD, discusses key considerations for second-line treatment selection for patients with melanoma who have progressed on PD-1 inhibitors.

Dr Moser on Treatment Considerations After Progression on Frontline PD-1 Inhibitors in Melanoma  

Although FDA-approved therapies such as lifileucel (Amtagvi) offer additional treatment options for patients with metastatic melanoma who received prior PD-1 inhibition, clinicians must consider a variety of patient-specific factors when deciding on the appropriate treatment for an individual patient, according to Stergios Moschos, MD.

In February 2024, lifileucel was granted accelerated approval by the FDA

 for the treatment of adult patients with unresectable or metastatic melanoma previously treated with a PD-1 antibody, and if 

 V600 positive, a BRAF inhibitor with or without a MEK inhibitor. The regulatory decision was supported by data from the phase 2 C-144-01 trial (NCT02360579), which demonstrated that patients who received the recommended dose of lifileucel (n = 73) achieved an objective response rate (ORR) of 31.5% (95% CI, 21.1%-43.4%); the median duration of response (DOR) was not yet reached (NR; 95% CI, 4.1 months-NR).

“[Oftentimes], patients who receive cellular therapies such as lifileucel are a special kind,” Moschos, an associate professor of medicine in the Department of Medicine of the Division of Oncology at the University of North Carolina School of Medicine in Chapel Hill, said in an interview with 

. “Patients [with] metastatic melanoma that is not proliferating very fast [are good candidates for lifileucel] because the process of [manufacturing the agent] takes [time].”

In the interview, Moschos discussed his approach to treating patients with metastatic melanoma who experience disease progression following checkpoint inhibitor therapy, the current role of cellular therapies in the space, and notable ongoing clinical trials examining agents in the post–PD-1 inhibitor setting.

What are some of the current challenges of treating patients with metastatic melanoma, particularly in those who experience disease progression after a checkpoint inhibitor–containing regimen?

 It’s important to note that not every patient [with melanoma] is eligible for immunotherapy. Immunotherapy is nice, but it shouldn’t be taken for granted. [In terms of immunotherapy], we specifically talk about a class of agents called immune checkpoint inhibitors, which target [1 of] 3 proteins: PD-1, CTLA-4, and LAG3.

If [a patient] is refractory to [treatment with] a PD-1 inhibitor, they have approximately a 25% to 30% chance of responding to a CTLA-4 inhibitor. Most of the data [are with] ipilimumab [Yervoy], but it has to be given in combination with nivolumab [Opdivo], otherwise the regimen is not effective. [Patients] who are refractory to [treatment with] a PD-1 inhibitor can receive a LAG3 inhibitor; the only FDA-approved [regimen] is relatlimab-rmbw plus nivolumab [Opdualag].

What characteristics are you looking for when considering the use of cellular therapy in patients with melanoma, and how could 5-year follow-up data from the C-144-01 study will be presented at the 2025 ASCO Annual Meeting help further inform patient selection?

[There is] a single FDA-approved cellular therapy, lifileucel, which is an adoptive T-cell therapy. Lifileucel has to pass quality control testing, and it has to have at least 7.5 billion cells. Just because you’re able to grow lymphocytes from the tumor does not necessarily mean that this [manufactured product will be considered] a licensed product.

Patient selection is key, and not every patient can [receive this therapy]; these are the patients from whom you [must] harvest tumor [cells] from subcutaneous lesions and lymph nodes because it has not been well studied whether you can grow immune cells from liver, lung, or brain lesions. [Moreover], just because the first scan at 6 weeks shows [tumor] shrinkage, it does not necessarily mean that it will be an ongoing response, because a proportion of these patients do relapse.

We have found that patient selection is very important. Personally, I have found that the key to bringing patients to receiving cellular therapy lies in the use of effective bridging therapy. Bridging therapy is a means to reduce the tumor burden to a level where the effect of the cellular therapy will be greater. It is an extremely dangerous path for [a patient] with uncontrolled tumor growth or high tumor burden to be brought to lymphodepletion followed by cellular therapy because they can potentially die from the toxicities of the lymphodepleting regimen.

It is essential that the moment you identify a patient for adoptive T-cell therapy to identify a bridging therapy. Following [disease] progression after a MEK or PD-1 inhibitor, adding pembrolizumab [Keytruda] plus lenvatinib [Lenvima] should hopefully decrease the tumor burden. The beautiful thing with lenvatinib plus pembrolizumab is that once a patient responds, the median DOR is approximately 9 months. This is 9 months where you are able to bring your patient to a level of tumor burden ideal for cellular therapy to have an effect. I also [use this approach] to increase the chance of having a successful tumor harvest, because VEGF inhibition is important to increase tumor infiltrating lymphocyte [TIL] density. There have been studies that have shown that tumors with a high gene expression signature are non-inflamed. By suppressing the VEGF pathway, you increase the influx of TILs and [thus] increase the chance that you have a successful harvest.

Depending on the circumstances, once patients recover from cellular therapy, I may elect to put them back on bridging therapy until the first scan 6 weeks after the cellular therapy infusion to help those cells have more of an effect. The use of effective bridging therapy is something that perhaps has not been fully described; the study [which] led to the FDA approval [did not use] any bridging therapy. An effective bridging therapy will both increase the [chance of] a successful harvest and decrease the tumor burden to render those cell therapies more effective.

What are some therapeutic alternatives for patients who are not candidates for cellular therapy?

If a patient cannot go through the complex process of adoptive T-cell therapy with lifileucel [an] effective [option] is treating them with pembrolizumab plus lenvatinib. Patients with PD-1–refractory [disease] can have up to 25% to 30% response rates [with this approach]. This is an overlooked, less-marketed treatment but it’s very effective with the ability to shrink tumors and [display] clinical benefit within 1 to 2 weeks.

Another [approach] that is of growing interest is with cellular therapies where you perform leukapheresis and extract CD8-[expressing] cells from the peripheral blood and genetically engineer them to express a viral vector. This class of therapies [uses] a T-cell receptor that recognizes a particular a particular epitope. This treatment must be restricted to patients who have an HLA haplotype that is specific to recognize this receptor. The treatment [in this category] that is the most advanced in clinical development is IMA203. In a single-arm, phase 1/2 trial [NCT03686124] of patients with HLA-A*02:01–positive disease, it [displayed promising] response rates. Everything else [in this class] remains investigational.

Another trial that has generated a lot of interest is [examining] the second-generation oncolytic viral therapy, RP1. 

In the single-arm, phase 1/2 IGNYTE study

 [NCT03767348] of patients with PD-1 inhibitor–refractory disease, the addition of RP1 to [nivolumab] has produced an ORR of [approximately] 30% to 35%. [However], we need to be careful because in the phase 3 IGNYTE-3 study [NCT06264180], the number of prior treatments permitted is 2. There’s a difference between patients who have undergone 4 lines of therapy and those who have gone through 2.

[In fact], things are getting so competitive that the FDA has required trials that test agents in the PD-1–refractory setting to occur in a randomized fashion. The trial of IMA203 is a randomized study, the first of its kind in a solid tumor, where a cellular product is being tested against a menu of options. It is also interesting that when these immunotherapies are being tested in a randomized study, [patients in] the control arm [often] cannot receive targeted therapies. It’s interesting that in the physician’s mind, targeted therapies are used more as bridging therapy because [many patients] will ultimately develop resistance to targeted therapy.

Are there any other ongoing clinical trials evaluating targeted therapies in the melanoma space that you find notable?

In the targeted therapy space, there has been some stagnation with respect to adding a third drug to a BRAF/MEK inhibitor backbone. We have had a lot of failures, either because we were not able to escalate the third drug to a biologically effective dose or because the toxicity was very high.

Right now, the only third drugs that can be added to a BRAF/MEK inhibitor backbone are coming from phase 2 studies, such as adding hydroxychloroquine or a BCL-2 inhibitor to dabrafenib [Tafinlar] and trametinib [Mekinist] or a PD-1/PD-L1 inhibitor to a BRAF/MEK inhibitor backbone. There have [also] been smaller studies where a multi-targeted VEGF inhibitor [such as] regorafenib [Stivarga] has been added to a BRAF/MEK inhibitor [regimen] for patients with refractory melanoma [with] brain metastases. Interestingly, there was a recent phase 2 study [NCT02681549] of VEGF inhibitors with immunotherapy that combined bevacizumab with pembrolizumab in patients with PD-1 inhibitor–naive melanoma [with] brain metastases.

 Q61K mutations, has been much more challenging because single-agent MEK inhibition has not been effective. Therefore, the development [of treatments] is heavily relying on pan-RAF inhibitors, with a handful of them receiving accelerated approval [from the FDA] in combination with a MEK inhibitor. This is a double blockade of the MEK pathway using a pan-RAF and a MEK inhibitor.

In the PD-1 inhibitor–refractory space for patients with 

-mutated disease, there has been much less progress In the field of melanoma [with] brain metastases. Introducing bevacizumab with immunotherapy has proved to be a safe option with respect to intracranial hemorrhoids and as a means to spare patients from receiving corticosteroids, which we know suppress the immune system. The introduction of bevacizumab as—at the very least—a steroid-sparing agent may potentially be safe and effective in certain patient subgroups.

FDA grants accelerated approval to lifileucel for unresectable or metastatic melanoma. FDA. February 16, 2024. Accessed April 30, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-lifileucel-unresectable-or-metastatic-melanoma

Stergios Moschos, MD, discusses his approach to selecting from the available agents in metastatic melanoma after first-line PD-1 inhibition.

Patient Selection Is Crucial for Treatment Decisions in Metastatic Melanoma After PD-1 Inhibition

Stergios J. Moschos, MD, discusses how the use of bridging therapy can enhance the efficacy of adoptive T-cell therapies for patients with melanoma.

"Bridging therapy is a means to reduce the tumor burden to a level that [makes] the effect of the cellular therapy greater. [Cellular therapy] is a dangerous path for someone with uncontrolled growth of their tumor…[therefore,] it is essential that the moment that you identify the patient going [to receive] adoptive T-cell therapy, [you] identify a bridging therapy."

Stergios J. Moschos, MD, an associate professor of medicine in the Department of Medicine in the Division of Oncology at the University of North Carolina (UNC) Chapel Hill School of Medicine, UNC Health, emphasized the importance of appropriately administering bridging therapy to patients who are slated to receive the adoptive T-cell therapy lifileucel (Amtagvi).

Patient selection plays a critical role in the successful administration of adoptive T-cell therapies, Moschos began. One key determinant of successful treatment is the use of effective bridging therapy to reduce tumor burden prior to lymphodepletion and cell infusion, Moschos stated. The rationale behind bridging therapy is to achieve disease control and minimize tumor burden, thereby enhancing the efficacy of cellular therapy and reducing the risk of treatment-related toxicities, he explained.

Patients with rapidly progressive disease or a high tumor burden are at elevated risk for severe toxicity during lymphodepleting chemotherapy, which may compromise their ability to receive or benefit from subsequent cell therapy, Moschos stated. Therefore, early identification of appropriate bridging strategies is essential once a patient is deemed a candidate for cellular therapy, he reiterated. Therapeutic agents used during this period may include a MEK inhibitor, a PD-1 inhibitor, or lenvatinib (Lenvima), Moschos outlined.

Notably, the combination of lenvatinib and pembrolizumab (Keytruda) has demonstrated a median duration of response of approximately 9 months in various tumor types, Moschos reported. This extended response window can provide oncologists with valuable time to lower disease burden and optimize the patient’s overall condition prior to proceeding with lifileucel, he stated. Ultimately, careful sequencing of therapies, including the timely integration of bridging regimens, can significantly influence outcomes and should be considered a fundamental component of cellular therapy planning, Moschos concluded.

Dr Moschos on Treatment Strategies With Adoptive T-Cell Therapy in Melanoma

A dive into treatment considerations and ongoing research for advanced melanoma after PD-1 inhibition.

Treatment Considerations and Evolving Data in Advanced Melanoma After Checkpoint Inhibition | Supplements and Featured Publications

Lifileucel Paves the Way for Evolving Treatment Approaches After PD-1 Inhibition in Advanced Melanoma

Dr Moser on Treatment Considerations After Progression on Frontline PD-1 Inhibitors in Melanoma

Patient Selection Is Crucial for Treatment Decisions in Metastatic Melanoma After PD-1 Inhibition

Dr Moschos on Treatment Strategies With Adoptive T-Cell Therapy in Melanoma