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CHEMOSAT Clinical Outcomes

For HCPs / Clinical Outcomes

Read the FOCUS manuscript

Watch Dr. Matthew Wheater discuss the key elements of the FOCUS data

Learn about the FOCUS study

Dr. Matthew Wheater

Consultant Medical Oncologist, University Hospital Southampton

Dr Wheater provides an overview of the FOCUS study, which included 91 metastatic uveal melanoma patients. Dr Wheater explains the study design, patient selection and study outcomes.

The FOCUS study was the largest LDT (liver directed therapy) clinical trial undertaken in metastatic uveal melanoma.1-3

95 Patients were enrolled into the CHEMOSAT arm; 91 patients received treatment.4,a

Patients could have limited extrahepatic disease in the bone, subcutaneous sites, lymph nodes, or lung if the life-threatening component of the UM was in the liver. Any extrahepatic disease needed to be amenable to resection or radiation, with a defined treatment plan.4

Treatment schedule

Patients received a dose of 3 mg/kg of melphalan using CHEMOSAT delivery system every 6 to 8 weeks for up to 6 treatment cycles.4,a

  • Patients received a median of 4 treatment cycles (range, 1-6 cycles)
  • The maximum of 6 treatment cycles was received by 37% of the 91 treated patients

a Based on ideal body weight (IBW; maximum total dose, 220 mg)

More Than 1/3 of Patients Responded to Treatment With CHEMOSAT4

ORR reported in FOCUS was 36.3% (n = 33)4

  • Complete response (CR): 7.7% (n = 7)4
  • Partial response (PR): 28.6% (n = 26)4

Median DoR in responders (n = 33) was 14 months4,c

ORR4
Responders in FOCUS trial (n=33)4

CR: Disappearance of all target lesionsa
PR: ≥30% Decrease in the sum of the long axis diameter of tumor target lesionsb

aAny pathological lymph nodes (target or nontarget) must be <10 mm in short-axis diameter. For nontarget lesions, disappearance of all nontarget lesions and normalization of tumor marker level.5
bUsing the baseline sum as reference.5
cCalculated using Kaplan-Meier method.4

Safety: Demonstrated
Safety & Tolerability4

Most common adverse events (>30% of patients)

• Nausea  • Fatigue  • Musculoskeletal pain
• Abdominal pain  • Vomiting

All adverse events observed at a frequency of >10% in patients

All grades, % Grades 3 or 4, %
Gastrointestinal disorders
Nausea 57 0
Abdominal paina 39 1
Vomitinga 35 0
Diarrheaa 17 1
General disorders
Fatiguea 65 0
Pyrexiaa 16 0
Musculoskeletal and connective tissue disorders
Musculoskeletal paina 46 1
Groin pain 11 0
Respiratory disorders
Dyspneaa 23 2
Cougha 15 0
Nervous system disorders
Headachea 19 0
Lethargy 12 0
Dizzinessa 11 0
Injury and procedural complications
Contusion 17 0
Metabolism and nutrition disorders
Decreased appetite 16 0
Vascular disorders
Hemorrhagea 15 1
Hypotensiona 13 3

aRepresents a composite of multiple, related preferred terms.

Serious adverse events occurred in 45% of patients who received treatment4

Serious adverse events occurring in ≥2% of patients were thrombocytopenia (10%), neutropenia (8%), febrile neutropenia (7%), platelet count decreased (6%), leukopenia (4.2%), cardiac arrest (3.2%), neutrophil count decreased (2.1%), hypoxia (2.1%), pleural effusion (2.1%), pulmonary edema (2.1%), and deep vein thrombosis (2.1%).4

Fatal adverse events occurred in 3 patients (3.2%) ; these included cardiac arrest, acute hepatic failure, and bacterial peritonitis and were deemed not to be related to treatment.4,6

Treatment was permanently discontinued because of adverse events in 18% of patients, with neutropenia being the most common reason (3.2%).4

Combination Therapy

Initial data from the Phase 1B CHOPIN study has shown an ORR of 85.7% using a combination of CHEMOSAT and ipilimumab plus nivolumab.

Prospective & Retrospective Studies

Treatment naïve as well as previously treated patients have shown efficacy across various endpoints.

N Treatment Line Patient Tumor Characteristics ORR OS PFS Safety Reference
Prospective Study 35 60%
treatment naïve 		No. of metastases ≥10 (57%) 72% 1 year OS - 77%
2 year OS - 43%
mOS 19.1 months 		7.5
mPFS		 Majority developed grade 3/4 haematologic events
14 grade 3 non-haematologic events		 Meijer, T., et al 20207
Retrospective Studies 81 54%
treatment naïve 		>10 lesions/>50% volume replacement (51.9%) 60.5% mOS 14.9 months 8.4
mPFS		 Grade 3/4 events were observed in 27.7% of patients Modi, S., et al 20228
51 43.1%
treatment naïve 		Oligometastatic disease ≤ 3 deposits (23.5%)
>10 lesions/>50% volume replacement (31.4%)		 47% mOS 15.3 months 8.1
months		 37.5% grade 3-4 non-haematologic events Karydis, I., et al 20171
19 31%
treatment naïve 		Not reported 53% mOS 16.7 months 14.03
months		 2 cases grade 3a (coronary ischaemia)
1 case grade 3b (transfemoral bleeding with following surgery)		 Bruning, R., et al 20202
16 25%
treatment naïve 		Hepatic lesions ranged from 3 to >20
Median tumour load of 22.5% (interquartile range 10 to 25%)		 60% mOS 27.4 months 11.1
mPFS		 Grade 3/4 events were observed in 43.8% of patients Artzner, C., et al 20199

ORR – overall response rate; PFS – progression free survival; mPFS – median progression free survival, OS – overall survival; mOS – median overall survival.

Summary of CHEMOSAT Publications

Clinical & Scientific Publications

CHEMOSAT in other tumour types

To date, over 250 patients with various types of malignancies, such as ICC & CRC have received CHEMOSAT in centres across Europe.

To get involved in our upcoming studies please email EUMedicalAffairs@delcath.com