Experts Weigh In on Some of the Most Impactful Data in Melanoma From ASCO 2026

During the 2026 ASCO Annual Meeting, OncLive® connected with experts to highlight impactful findings in melanoma and explore their potential clinical relevance. Find their insights below.

Darovasertib plus crizotinib vs investigator’s choice as first-line treatment for patients with HLA-A2 negative metastatic uveal melanoma: Primary results from the OptimUM-02 trial (Abstract LBA9503)

The combination of darovasertib and crizotinib (Xalkori) led to a clinically meaningful and statistically significant improvement in progression-free survival (PFS) vs investigator’s choice of therapy in patients with HLA-A*02:01–negative metastatic uveal melanoma, meeting the primary end point of the phase 3 OptimUM-02 trial (NCT05987332).

At a median follow-up of 7.4 months, the median PFS was 6.9 months (95% CI, 5.6-8.3) in the combination arm vs 3.1 months (95% CI, 1.8-4.2) in the control arm per blinded independent central review (HR, 0.42; 95% CI, 0.30-0.59; P < .0001). The median investigator-assessed PFS was 6.7 months (95% CI, 5.6-8.2) and 2.7 months (95% CI, 1.7-4.1), respectively (HR, 0.36; 95% CI, 0.26-0.50; P < .0001). Additionally, PFS favored the combination in subgroup analysis, irrespective of age, gender, ECOG performance status, largest single target lesion size, and metastatic pattern.

Matteo Carlino, BMedSc, MBBS, FRACP, Melanoma Institute Australia

“For my field, the uveal melanoma study presented by Dr Marlana Orloff showing the benefit of darovasertib and crizotinib over immunotherapy in HLA-A*02:01–negative patients is the most practice-changing melanoma study. I truly think it will change practice very soon, definitely in the US and hopefully in places like Australia.”

Kalijn Bol, PhD, Radboud University Medical Center Nijmegen, Netherlands

“We saw very interesting data in uveal melanoma, which is a super rare subset of patients with melanoma, where the combination of darovasertib and crizotinib showed nice results in a phase 2/3 clinical trial. I think these medications will become available for patients in the near future.”

Meredith McKean, MD, MPH, Sarah Cannon Research Institute

“[I would say a big milestone is] the phase 3 results for patients with metastatic uveal melanoma that are HLA-A*02:01–negative [who] evaluated darovasertib and crizotinib vs investigator’s choice therapy. These patients have not had any FDA-approved therapies. It's really been a challenging treatment landscape for patients with metastatic uveal melanoma [who] are not eligible for tebentafusp-tebn [Kimmtrak], so we were certainly excited to see the phase 3 registrational trial results demonstrating benefit with that combination.”

Daniel Olson, MD, University of Chicago

“What is probably going to change practice relatively soon is [the data] in uveal melanoma. We mostly talk about cutaneous melanoma because it's more prevalent and has a bigger epidemiological impact, but uveal melanoma is a bad-acting subset of melanoma that has a very different behavior than cutaneous melanoma, and it's been very challenging to treat. There is a targeted therapy, a PKC inhibitor, darovasertib, combined with crizotinib, and it's given to patients with HLA-A*02:01–negative disease, or patients that are not matched for [T-cell receptor] therapies, which [includes] most patients. This is the first targeted therapy that we have in uveal melanoma. Within uveal melanoma, we have a breakdown in our systemic therapies. We've got the patients with HLA-A*02:01–positive status [who] can get tebentafusp. But the patients who are not HLA-matched don't really have a good systemic therapy. Historically, we've given combination checkpoint inhibitors like ipilimumab [Yervoy] and nivolumab [Opdivo], but response rates are poor, so they haven't had good options. This combination looks like it might be a good option. Response rates are relatively high, and the PFS is good, so the data look really encouraging. We expect that this will…become an available therapy soon.”

Marlana M. Orloff, MD, Thomas Jefferson University

“This is a large, randomized, multicenter, global trial that has shown a statistically significant improvement in PFS for a targeted therapy, so it checks the boxes of a lot of things we were lacking: therapies for patients with HLA-A*02:01–negative disease and a targeted therapy. It could lead to an approval that will be practice-changing for our patients.”

Individualized neoantigen therapy intismeran autogene (intismeran) plus pembrolizumab (pembro) in resected melanoma: 5-year update of the KEYNOTE-942 study (Abstract 9500)

Intismeran autogene (intismeran; formerly known as mRNA-4157 or V940) plus pembrolizumab (Keytruda) continued to demonstrate durable and clinically significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared with pembrolizumab alone in patients with resected high-risk melanoma, according to data from the 5-year planned follow-up analysis of the phase 2 KEYNOTE-942 study (NCT03897881).

At the December 15, 2025, data cutoff, RFS events occurred in 26.2% of patients receiving intismeran plus pembrolizumab (n = 107) vs 46.0% in the pembrolizumab-alone arm (n = 50), corresponding to an HR of 0.510 (95% CI, 0.294-0.887). DMFS events occurred in 14.0% of patients who received the combination vs 30.0% of those in the monotherapy arm. There was a 59% reduction in the risk of distant metastasis or death (HR, 0.411; 95% CI, 0.200-0.843). Overall survival (OS) data remain immature, although a trend in favor of the combination was observed. OS events occurred in 6.5% vs 14.0% of patients in the combination vs monotherapy arms, respectively (HR, 0.471; 95% CI, 0.165-1.345).

Intismeran plus pembrolizumab maintained a manageable safety profile at 5-year follow-up with no new safety signals identified and no potentiation of immune-related adverse effects relative to pembrolizumab monotherapy.

Hussein Tawbi, MD, PhD, The University of Texas MD Anderson Cancer Center

“We saw the 5-year update on the intismeran autogene data, which showed that there are persistent benefits in the adjuvant setting. I don't think that abstract has a ton of inherent value, but it sets us up for the fact that we're waiting for the phase 3 trial and maybe the only approach in the adjuvant setting that may have an impact beyond checkpoint inhibitors. So that may be one of the exciting pieces.”

OBX-115 engineered tumor-infiltrating lymphocyte (TIL) cell therapy with regulatable membrane-bound IL15 (mbIL15) in patients with advanced melanoma that has progressed on/after immune checkpoint inhibitors (ICI): Phase 2 results (Abstract 9507)

Results from the phase 1/2 Agni-01 study (NCT06060613) showed that the patients treated at the recommended phase 2 dose of OBX-115 (n = 15), an engineered tumor-infiltrating lymphocyte (TIL) cell therapy expressing regulatable membrane-bound IL-15, achieved an objective response rate of 67% (95% CI, 38%-88%). This included 2 complete responses (13%) and 8 partial responses (53%). The disease control rate was 93%, and the median duration of response had not been reached at a median follow-up of 4.3 months (range, 2.3-16.9 months).

From a safety standpoint, grade 3 or higher non-hematologic adverse effects were uncommon; cytokine release syndrome was reported in 33% of patients. There were no dose-limiting toxicities and no immune effector cell-associated neurotoxicity syndrome.

Hussein Tawbi, MD, PhD, The University of Texas MD Anderson Cancer Center

“The Obsidian T-cell therapy is very impressive. This is going to be a very important option treating patients with cell therapy that's engineered, that allows you to skip or not use IL-2 and seems to have some impressive benefit as well.”

James Smithy, MD, MHS, Memorial Sloan Kettering Cancer Center

“The Obsidian expansion data are very exciting, even though they’re from a limited number of patients. The response rate in that cohort is very impressive, and there seems to be some durable responses. We need additional cell therapy options for patients who have refractory disease after checkpoint blockade.”

Daniel Olson, MD, University of Chicago

“We received some updates from interesting therapies that are coming out that are not going to change practice immediately but really have us looking toward the future and what this post–PD-1 space will be. One that we're very interested in is OBX-115, which is a cytokine-engineered TIL therapy that has a membrane-bound IL-15, so it doesn’t require IL-2. We’ve seen previous updates at past ASCO meetings, with relatively small numbers of patients, but with a high response rate. TIL therapy is a multi-antigen targeting therapy, so every patient has a unique set of T cells recognizing personal neoantigens, so we’re not just targeting a single antigen. While PRAME-directed therapies are very interesting and are [likely] going to drive some disease control, TIL therapy gives us the possibility of [a] cure, which we couldn't really talk about in the second line or checkpoint beyond space. Seeing that consistent high response rate with TIL therapy has a lot of us very excited that once we get through checkpoint inhibitors, we're still going to have an opportunity [to achieve [a] cure for some patients. Even though that study has a lot more patients to treat, and we have to see the long-term signals, [the] preliminary data [are encouraging].”

Patient-level clinical response dynamics in advanced melanoma with anzutresgene autoleucel (anzu-cel), a PRAME-directed T-cell receptor (TCR) T-cell therapy (Abstract 9508)

Anzutresgene autoleucel (anzu-cel, IMA203), a PRAME-directed T-cell receptor (TCR) T-cell therapy, produced a confirmed objective response rate (cORR) of 56% among evaluable patients in the all-melanoma population (n = 32), according to data on patient-level clinical response dynamics from the phase 1/2 IMA203-101 trial (NCT03686124). In the overall population (n = 33), the ORR was 64%, and the disease control rate was 91%. By subtype, the cORR was 50% in cutaneous melanoma (n = 14) and 67% in uveal melanoma (n = 15). The median time to best overall response was 1.4 months (range, 1.2-2.8), with most responders exhibiting tumor shrinkage at the first scan. The median duration of response across the all-melanoma cohort was 14.6 months (range, 4.2-38.2+), with a median follow-up of 18.7 months.

The agent’s safety profile was predictable and manageable; the most common treatment-emergent adverse effects (AEs) were anticipated cytopenias associated with lymphodepletion, and immune-mediated AEs of special interest occurred by day 30 postinfusion and were largely manageable.

Daniel Olson, MD, University of Chicago

“In the PRAME space, there’s the IMA203 TCR T-cell therapy. Unlike brenetafusp [IMC-F106C], it’s a T-cell receptor engineered into T cells and given as a cell therapy. From the previously [reported] phase 1 data, we know that this [agent can produce] a very high response rate in PRAME-expressing tumors like melanoma. There's an ongoing randomized phase 3 study now [evaluating anzu-cel], but some updates from the initial phase 1 data look really promising.”

ADAM trial: A multicenter, randomized, double-blinded, placebo-controlled, phase 3 trial of adjuvant avelumab (anti-PD-L1 antibody) in patients with Merkel cell carcinoma and lymph node metastases (Abstract LBA9504)

In the phase 3 ADAM trial (NCT03271372), adjuvant treatment with avelumab (Bavencio) led to a numerical improvement in relapse-free survival (RFS) compared with placebo in patients with Merkel cell carcinoma and lymph node metastases (stratified HR, 0.61; 95% CI, 0.32-1.16; P = .132; stratified HR (age adjusted), 0.55; 95% CI, 0.28-1.06; P = .075).

Patients treated with avelumab (n = 48) achieved a 1- and 2-year RFS rate of 87.2% (95% CI, 73.8%-94.1%) and 78.7% (95% CI, 64.1%-87.9%), respectively. These respective rates in the placebo arm (n = 52) were 59.6% (95% CI, 46.1%-71.5%) and 57.7% (95% CI, 43.2%-69.7%).

Shailender Bhatia, MD, Fred Hutch Cancer Center:

“I would propose that our study is going to be informative. One thing that we are missing out on in most adjuvant and neoadjuvant trial discussions is that we are focusing on the short-term end points of relapse-free survival, but as the Merkel cell data point out, that does not necessarily mean that we have to treat all of our patients with adjuvant therapy. We need to strive for longer-term survival benefit when it comes to adjuvant therapy.”

Response-focused analyses of the impact of circadian rhythm on efficacy of first-line immunotherapy in melanoma (Abstract 9520)

Findings from retrospective response-focused analyses showed that in patients with advanced melanoma who received first-line treatment with immune checkpoint inhibitor–based therapy, overall response rates (ORRs) did not differ among patients who received treatment prior to 1 pm (early cohort) vs those given treatment after 1 pm (late cohort).

Patients in the early cohort (n = 78) achieved an ORR of 64% (95% CI, 52%-74%) compared with 62% (95% CI, 53%-70%) for patients in the late cohort (n = 138; adjusted OR, 1.05; 95% CI, 0.57-1.97; P = .87). Rates of complete response (35% vs 29%, respectively) and partial response (29% vs 33%) were similar between the 2 groups.

Shailender Bhatia, MD, Fred Hutch Cancer Center:

“We also presented an abstract on the timing of immunotherapy infusions. That has been a hot area lately, and a lot of studies have pointed out that morning or early infusions of immunotherapy might have better outcomes, which a lot of clinics are now thinking about adopting, which poses huge logistical challenges. We looked at that data in our center, and we have been using immunotherapy for at least 15 years, and we saw no difference in the outcomes based on the timing of immunotherapy infusions. That makes intuitive sense based on the mechanism of action of these drugs and the fact that these antibodies last in the serum for months after administration. I’m hoping we will stir some more conversation in that controversial field.”