NCCN Guidelines for Melanoma: Uveal V.1.
2022–Interim on 03-07-22
Guideline Page
and Request
UM-2, UM-4, UM-5, UM-6
External request:
Submission from Immunocore (10/29/21)
to consider the following clinical evidence
supporting the addition of information
regarding tebentafusp-tebn and make the
following suggested changes:
• UM-6 (Distant Metastatic Disease):
under “Treatment of Metastatic Disease”,
add tebentafusp (preferred, category 1) if
HLA-A*02:01-positive
• Footnote mm (UM-6): Replace first
sentence with “Tebentafusp is the first
therapy to demonstrate significant overall
survival improvement in patients with
uveal melanoma in a phase 3
randomized controlled trial.”
• UM-6 (Metastatic Disease), UM-5
(Recurrence), UM-4 (Post-Risk
Stratification), UM-2 (Diagnosis),
Workup: Add HLA testing
Panel Discussion/References Vote
YES NO ABSTAIN ABSENT
Based on a review of the data, the Panel consensus was as noted below:
• UM-6 (Distant Metastatic Disease): Under “Treatment of Metastatic
Disease”, add tebentafusp (preferred, category 1) if HLA-A*02:01-
positive
o The panel did not make the noted change, instead, the
addition of tebentafusp-tebn was made on page UM-C as
noted below.
• UM-6; Footnote mm : Replace first sentence with “Tebentafusp is the
first therapy to demonstrate significant overall survival improvement in
patients with uveal melanoma in a phase 3 randomized controlled
trial.”
o Based on a review of the data and discussion, the panel did 21 2 2 6
not use the language proposed in the submission. However,
the panel supported adding the following language: In general,
there are no systemic therapies that have reliably improved
the overall survival in patients with metastatic uveal
melanoma; however, individual patients may derive
substantial benefit on occasion. A recently reported phase III
randomized trial was conducted in previously untreated HLA
A*02:01-positive patients with metastatic uveal melanoma.
Patients were randomized to tebentafusp-tebn (a bispecific
protein) or investigator’s choice of either pembrolizumab,
ipilimumab, or dacarbazine. Treatment with tebentafusp-tebn
resulted in longer overall survival compared to control therapy.
Agents that are effective for metastatic cutaneous melanoma
may be used (preferably on clinical trial) as first line therapy
for HLA-A* 02:01-negative patients and post-first line failure
after tebentafusp-tebn for HLA-A* 02:01-positive patients. If
disease is confined to the liver, regional therapies such as
chemoembolization, radioembolization, or
immunoembolization should be considered. Since
tebentafusp-tebn response rates are low, symptomatic
patients may be better palliated by liver-directed treatment first
or respond better to ipilimumab/nivolumab. See Systemic
Therapy for Metastatic or Unresectable Disease (UM-C).
• UM-6 (Metastatic Disease), UM-5 (Recurrence), UM-4 (Post-Risk
Stratification), UM-2 (Diagnosis), Workup: Add HLA testing
o The Panel consensus was to defer the request until a later
date.
See submission for references.
NCCN Guidelines for Melanoma: Uveal V.1.2022–Interim on 03-07-22
Guideline Page
and Request
UM-C
Internal request:
In response to the FDA approval of
tebentafusp-tebn for the treatment of HLA-
A*02:01-positive adult patients with
unresectable or metastatic uveal melanoma
the panel requested the addition of
tebentafusp-tebn for this indication.
External request:
Submission from Immunocore (10/29/21)
to consider the following clinical evidence
supporting the addition of information
regarding tebentafusp-tebn and make the
following suggested changes:
• UM-C 1 (Systemic Therapy for Distant
Metastatic Disease): under preferred
regimens, add tebentafusp as category 1
for HLA-A*02:01-positive metastatic
disease
• Footnote a (UM-C): Replace first
sentence with “Tebentafusp is the first
therapy to demonstrate significant overall
survival improvement in patients with
uveal melanoma in a phase 3
randomized controlled trial.”
Panel Discussion/References Vote
YES NO ABSTAIN ABSENT
Based on a review of the data, the Panel consensus was as noted below:
• UM-C 1 (Systemic Therapy for Distant Metastatic Disease): under
preferred regimens, add tebentafusp as category 1 for HLA-A*02:01-
positive metastatic disease:
o Based on a review of the data in the noted reference, the 21 2 3 6
panel consensus was to include tebentafusp-tebn as a
systemic therapy option for distant metastatic disease in
patients who are HLA A*02:01-positive. This is a category 1,
preferred recommendation.
• Footnote a (UM-C): Replace first sentence with “Tebentafusp is the
first therapy to demonstrate significant overall survival improvement in
patients with uveal melanoma in a phase 3 randomized controlled
trial.”
o Based on a review of the data and discussion, the panel did 21 2 3 6
not use the language proposed in the submission. However,
the panel supported adding the following language: The
literature is not directive regarding the specific systemic
agent(s) offering superior outcomes, but does provide
evidence that uveal melanoma is sensitive to some of the
same systemic therapies used to treat cutaneous melanoma.
Although there are no systemic therapies that have reliably
improved the overall survival in patients with metastatic uveal
melanoma, individual patients may derive benefit on occasion.
Given the lack of positive phase III studies, clinical trials are
preferred. Tebentafusp-tebn was studied in a phase III
randomized trial in previously untreated, HLA A*02:01-positive
patients with metastatic uveal melanoma. Patients were
randomized to tebentafusp-tebn (a bispecific protein) or
investigator’s choice of either pembrolizumab, ipilimumab, or
dacarbazine. Results showed that treatment with tebentafusp-
tebn resulted in longer overall survival compared to control
therapy. The literature is not directive regarding other systemic
therapies. Individual patients with metastatic uveal melanoma
may derive benefit on occasion from agents used to treat
metastatic melanoma of cutaneous origin; clinical trials are
preferred given the lack of randomized data.
See submission for references.