Updated results in seven patients with advanced uveal
melanoma treated with CHEMOSAT and ipilimumab plus nivolumab show a
Median PFS of 29.1 months
All seven patients treated still alive as of last follow-up
at a median follow-up of 29.1 months
YORK, Jan. 17, 2023 /PRNewswire/ -- Delcath
Systems, Inc. (Nasdaq: DCTH), an interventional oncology
company focused on the treatment of primary and metastatic cancers
of the liver, today announced the publication of updated results
from the Phase 1b CHOPIN Trial,
conducted at Leiden University Medical Center on the use of
the Delcath CHEMOSAT® Hepatic Delivery System with
Melphalan (CHEMOSAT) in combination with the immune checkpoint
inhibitors (ICI) ipilimumab and nivolumab to treat patients with
metastatic uveal melanoma with liver metastases. The publication is
entitled "Combining Melphalan Percutaneous Hepatic Perfusion with
Ipilimumab Plus Nivolumab in Advanced Uveal Melanoma: First Safety
and Efficacy Data from the Phase 1b
Part of the CHOPIN Trial" and was published in Cardiovascular and
Updated CHOPIN Phase 1b Trial
The goal of the CHOPIN trial is to study the safety and
potential synergistic effects of systemic ICI therapy ipilimumab
plus nivolumab (IPI+NIVO) when combined with Delcath's proprietary
liver-targeted percutaneous hepatic perfusion (PHP) treatment in
metastatic uveal melanoma patients. The just released publication
presented updated safety and efficacy results from the Phase
1b portion of the trial which were
previously presented in June 2022 at
the American Society of Clinical Oncology Annual
Meeting. The Phase 1b portion of
the trial enrolled seven patients each of which were treated with
two courses of PHP (melphalan 3mg/kg, max 220 mg per cycle)
combined with four courses IPI+NIVO escalating the dosing from
1mg/kg each IPI+NIVO (cohort 1) to IPI 1mg/kg + NIVO 3mg/kg (cohort
2). As previously reported, the Best Overall Response included 1
complete response, 5 partial responses and 1 stable disease
accounting for an Objective Response Rate of 85.7% and a Disease
Control Rate of 100% (FIGURE 1). At the cut-off date of
November 15, 2022, the median
follow-up was 29.1 months (range 8.9 – 30.2), the median PFS was
29.1 months (95% CI 11.9 – 46.3) and the median duration of
response was 27.1 months (range 7.4 – 28.5). All patients are
still alive and three of four patients who subsequently experienced
PD continued with treatment in the form of repeated melphalan PHP
The ongoing randomized phase 2 part of the CHOPIN trial
comparing M-PHP alone with M-PHP plus IPI/NIVO, which will include
another 76 patients (38 per arm), is approximately 50% enrolled and
will provide more insight to the efficacy.
The determination of a safe and effective dose was a primary
goal of the Phase 1b portion of the
CHOPIN trial. Grade 1/2 adverse events were seen in all patients
and 71.4% experienced grade 3/4 toxicities. In this phase
1b dose-escalation study combining
M-PHP with IPI/NIVO the safe treatment dose was established at IPI
1mg/kg and NIVO 3mg/kg. The authors did observe low-grade
immune-related toxicities and PHP-related hematological toxicities
in the treated groups. Hematological toxicity is a common adverse
event after M-PHP, affecting approximately three-quarters of
patients. All 7 patients in the study experienced grade 1/2 anemia.
To prevent severe leukopenia/neutropenia, G-CSF was administered
within 48 hours after M-PHP in their treatment center. The phase 2
part of the CHOPIN study will provide more information on both
hepatic and systemic toxicity associated with the combination
"If similar results are observed in the larger, randomized
second phase of this trial, it would represent a meaningful
improvement over current treatment options for this patient
population," said Dr. Johnny John,
Senior Vice President, Medical and Clinical Affairs. "In
addition, further investigation of this combination protocol may be
warranted in patients with liver dominant disease in other tumor
types currently treated with ICI agents."
Rationale for Combination Therapy
The rationale for combining ICI therapy with M-PHP in metastatic
uveal melanoma is based on both uveal melanoma's specific
characteristics and the unique immunomodulatory role of the liver.
Uveal melanoma is characterized by a different set of driver
mutations and lower mutational load compared to cutaneous melanoma,
leading to limited neoantigen presentation and lower efficacy of
ICI (1). By combining M-PHP with IPI/NIVO, the authors noted that
they aim to increase the efficacy of ICI by turning a 'cold tumor'
into a 'hot tumor'. In addition, while PHP can provide long-lasting
disease control in the liver, it does not control extrahepatic
disease. Conversely, IPI/NIVO treatment shows a trend towards
control of extrahepatic lesions, but hepatic disease progression
regularly occurs (2, 3, 4). With combined treatment, the authors
aim to control hepatic disease, as well as prevent extrahepatic
disease in follow-up. In addition, it is well documented that the
liver has a unique immune modulating role and liver metastases
diminish ICI efficacy systemically regardless of the type of
primary tumor (5, 6, 7) and in animal models it has been shown that
this effect can be overcome by localized hepatic therapy (8).
Current available evidence from studies on isolated limb perfusion
(ILP) and isolated hepatic perfusion (IHP), which is the surgical
counterpart of M-PHP, show that ILP and IHP can lead to T-cell
activation following the procedures (9, 10). The authors
hypothesize that this is also the case for M-PHP leading to an
improved activation of the immune system together with ICI.
A PDF of the article abstract can be viewed by clicking
About Delcath Systems, Inc.
Delcath Systems, Inc. is an interventional oncology company
focused on the treatment of primary and metastatic liver cancers.
The company's proprietary percutaneous hepatic perfusion (PHP)
system is designed to administer high-dose chemotherapy to the
liver while controlling systemic exposure and associated side
effects. In the United States, the
PHP system is being developed under the tradename HEPZATO™ KIT
(melphalan hydrochloride for injection/Hepatic Delivery System), or
HEPZATO, for the treatment of patients with unresectable
hepatic-dominant metastatic ocular melanoma (mOM), also known as
metastatic uveal melanoma (mUM) and is considered a combination
drug and device product regulated as a drug by the United States
Food and Drug Administration (FDA).
In Europe, the PHP system is
now regulated as a Class lll medical device and is approved for
sale under the trade name CHEMOSAT Hepatic Delivery System for
Melphalan, or CHEMOSAT, where it has been used at major medical
centers to treat a wide range of cancers of the liver.
Safe Harbor / Forward-Looking Statements
The Private Securities Litigation Reform Act of 1995 provides a
safe harbor for forward-looking statements made by the Company or
on its behalf. This news release contains forward-looking
statements, which are subject to certain risks and uncertainties
that can cause actual results to differ materially from those
described. Factors that may cause such differences include, but are
not limited to, uncertainties relating to: the timing and results
of the Company's clinical trials, our determination whether to
continue a clinical trial program or to focus on other alternative
indications, and the impact of the COVID-19 pandemic on the
completion of our clinical trials; the impact of the presentations
at major medical conferences and future clinical results consistent
with the data presented; the Company's ability to successfully
commercialize the HEPZATO KIT/CHEMOSAT system and the potential of
the HEPZATO KIT/CHEMOSAT system as a treatment for patients with
primary and metastatic disease in the liver; our ability to obtain
reimbursement for commercialized product in various markets;
actions by the FDA or foreign regulatory agencies; the Company's
ability to successfully enter into strategic partnership and
distribution arrangements and the timing and revenue, if any, of
the same; uncertainties relating to the timing and results of
research and development projects; and uncertainties regarding the
Company's ability to obtain financial and other resources for any
research, development, clinical trials and commercialization
activities. These factors, and others, are discussed from time to
time in our filings with the Securities and Exchange Commission.
You should not place undue reliance on these forward-looking
statements, which speak only as of the date they are made. We
undertake no obligation to publicly update or revise these
forward-looking statements to reflect events or circumstances after
the date they are made.
Investor Relations Contact:
- Diener-West M, Reynolds SM, Agugliaro DJ, Caldwell R, Cumming
K, Earle JD, et al. Development of metastatic disease after
enrollment in the COMS trials for treatment of choroidal melanoma:
Collaborative Ocular Melanoma Study Group Report No. 26. Arch
- Pelster MS, Gruschkus SK, Bassett R, Gombos DS, Shephard M,
Posada L, et al. Nivolumab and Ipilimumab in Metastatic Uveal
Melanoma: Results From a Single-Arm Phase II Study. J Clin Oncol.
- Karydis I, Chan PY, Wheater M, Arriola E, Szlosarek PW,
Ottensmeier CH. Clinical activity and safety of Pembrolizumab in
Ipilimumab pre-treated patients with uveal melanoma.
- Rozeman EA, Prevoo W, Meier MAJ, Sikorska K, Van TM, van de
Wiel BA, et al. Phase Ib/II trial testing combined radiofrequency
ablation and ipilimumab in uveal melanoma (SECIRA-UM). Melanoma
- Xiao-Juan C, Aiqun R, Liang Z, En-Dian Z, Tao J. Pan-Cancer
Analysis Identifies Liver Metastases as Negative Predictive Factor
for Immune Checkpoint Inhibitors Treatment Outcome. Frontiers in
Immunology 12, (2021).
- Lee J, Mehdizadeh S, Smith J, Young A, Mufazalov I, Mowery C,
et al. Regulatory T cell control of systemic immunity and
immunotherapy response in liver metastasis. ScienceImmunology.
- Yu, J., Green, M.D., Li, S. et al. Liver metastasis restrains
immunotherapy efficacy via macrophage-mediated T cell elimination.
Nat Med 27, 152–164 (2021).
- Xin, B, Yang, M, Wu, P, Du, L, Deng, X, Hui, E, et al.
Enhancing the therapeutic efficacy of programmed death ligand 1
antibody for metastasized liver cancer by overcoming hepatic
immunotolerance in mice. Hepatology. 2022; 76: 630– 645.
- Johansson J, Kiffin R, Andersson A, Lindnér P, Naredi PL,
Olofsson Bagge R, et al. Isolated Limb Perfusion With Melphalan
Triggers Immune Activation in Melanoma Patients. Frontiers in
Oncology. 2018;8:570. https://doi.org/10.3389/fonc.2018.00570
- Johansson J, Siarov J, Kiffin R, Molne J, Mattsson J, Naredi P,
et al. Presence of tumor-infiltrating CD8(+) T cells and
macrophages correlates to longer overall survival in patients
undergoing isolated hepatic perfusion for uveal melanoma liver
metastasis. Oncoimmunology. 2020;9(1):1854519.
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SOURCE Delcath Systems, Inc.