NCT01213472

Evaluation of a New Anti-cancer Immunotherapy in Patients With Non-operable and Progressing Metastatic Cutaneous Melanoma

Completed Phase 1 Results posted Last updated 9 October 2019

What this trial tests

Phase 1 trial testing GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI) in Melanoma in 33 participants. Completed in 17 April 2018.

Timeline

31 January 2011

Primary endpoint
17 April 2018

17 April 2018

Quick facts

Lead sponsor	GlaxoSmithKline
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	33
Start date	31 January 2011
Primary completion	17 April 2018
Estimated completion	17 April 2018
Sites	24 locations across France, Italy, Netherlands, Austria, United Kingdom, Germany, Switzerland, Australia

Drugs / interventions tested

• GSK Biologicals' 2241658A Antigen-Specific Cancer Immunotherapeutic (ASCI) — full drug profile →

Conditions studied

• Melanoma — all drugs for Melanoma →

Sponsor

GlaxoSmithKline — full company profile →

Who can join

18 and older, any sex, with Melanoma. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Number of Patients With Severe Toxicities During the Study Treatment Period Primary · During the study treatment period (maximum duration = 49 months).

Severe toxicity was defined, according to the Common Terminology Criteria for Adverse Events (CTCAE) (version 4.0), as 1)an Antigen-Specific Cancer Immunotherapeutic (ASCI) related or possibly related Grade 3 or higher toxicity. Grade 3 myalgia, arthralgia, headache, fever, rigors/chills and fatigue (including lethargy, malaise and asthenia) should persist for 48 hours despite therapy to be taken into account and as 2)an ASCI related or possibly related Grade 2 or higher allergic reaction occurring within 24 hours of the dose administration.

Group	Value	95% CI
NY-ESO 1 Group	0

Number of Patients With the Best Overall Response in the Overall Population Primary · During the study treatment period (maximum duration = 49 months).

Best response was recorded from the start of treatment until disease progression. Response assessment was essentially based on a set of measurable lesions (target lesions \[TL\]), and any other lesions (non-target lesions \[NTL\]), both identified at baseline. Complete Response (CR)=disappearance of all TL or NTL; Partial Response (PR) = at least 30 percent (%) decrease in the sum of the longest diameter(LD) of TL compared to baseline, stable disease (SD) = neither sufficient shrinkage to qualify PR nor sufficient increase to qualify for Progressive disease (PD) compared with baseline; PD = at

Best response, CR

Group	Value	95% CI
NY-ESO 1 Group	3

Best response, PR

Group	Value	95% CI
NY-ESO 1 Group	2

Best response, SD

Group	Value	95% CI
NY-ESO 1 Group	2

Best response, SD/PR

Group	Value	95% CI
NY-ESO 1 Group	2

Best response, PD

Group	Value	95% CI
NY-ESO 1 Group	23

Best response, NE

Group	Value	95% CI
NY-ESO 1 Group	1

Clinical Response, Yes

Group	Value	95% CI
NY-ESO 1 Group	5

Clinical Response, No

Group	Value	95% CI
NY-ESO 1 Group	28

Number of Patients With Best Overall Response Including Mixed Response (MxR) and Slow Progressive Disease (SPD) Criteria Secondary · During the study treatment period (maximum duration = 49 months).

Patients with Slow Progressive Disease (SPD) status met the following criteria: patient's Eastern Cooperative Oncology Group (ECOG) performance status was 0 or 1, patient's lactate dehydrogenase (LDH) value was not greater than twice the normal upper limit, there was no appearance of visceral metastases other than in the lung, patients did not meet any of the criteria for permanent stopping of study treatment. Mixed response (MxR) criteria was defined as follows: at least 30% decrease in the longest diameter (LD) occurring in at least one target lesion recorded and measured at baseline. Such r

CR

Group	Value	95% CI
NY-ESO 1 Group	3

PR

Group	Value	95% CI
NY-ESO 1 Group	2

SD/PR

Group	Value	95% CI
NY-ESO 1 Group	2

MxR: SD with target lesion regression

Group	Value	95% CI
NY-ESO 1 Group	0

MxR: PD with target lesion regression

Group	Value	95% CI
NY-ESO 1 Group	3

MxR: PR with new lesion

Group	Value	95% CI
NY-ESO 1 Group	2

SD without mixed response

Group	Value	95% CI
NY-ESO 1 Group	2

PD with SPD criteria

Group	Value	95% CI
NY-ESO 1 Group	10

Number of Patients With Adverse Events (AEs) by Maximum Grade Secondary · During the study treatment period (maximum duration = 49 months).

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medical product, whether or not considered related to the medicinal product. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack efficacy), abuse or misuse.

Any event, Grade 1

Group	Value	95% CI
NY-ESO 1 Group	9

Any event, Grade 2

Group	Value	95% CI
NY-ESO 1 Group	21

Any event, Grade 3

Group	Value	95% CI
NY-ESO 1 Group	3

Any event, Grade 4

Group	Value	95% CI
NY-ESO 1 Group	0

Any event, Grade 5

Group	Value	95% CI
NY-ESO 1 Group	0

Number of Patients With Adverse Events (AEs) That Are Causally Related to Treatment Administration by Maximum Grade Secondary · During the study treatment period (maximum duration = 49 months).

An AE is any untoward medical occurrence in a clinical investigation patient, temporally associated with the use of a medical product, whether or not considered related to the medicinal product. An AE can be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. For marketed medicinal products, this also includes failure to produce expected benefits (i.e. lack efficacy), abuse or misuse.

Any event, Grade 1

Group	Value	95% CI
NY-ESO 1 Group	20

Any event, Grade 2

Group	Value	95% CI
NY-ESO 1 Group	13

Any event, Grade 3

Group	Value	95% CI
NY-ESO 1 Group	0

Any event, Grade 4

Group	Value	95% CI
NY-ESO 1 Group	0

Any event, Grade 5

Group	Value	95% CI
NY-ESO 1 Group	0

Number of Patients With Serious Adverse Events (SAEs) by Maximum Grade Secondary · During the study treatment period (maximum duration = 49 months).

A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient, is a grade 4 AE according to the Common Terminology Criteria for Adverse Events (CTCAE, v 4.0), in addition, in this study, Grade 3 or higher pIMDs were considered as medically significant and were therefore notified as SAE.

Any event, Grade 1

Group	Value	95% CI
NY-ESO 1 Group	0

Any event, Grade 2

Group	Value	95% CI
NY-ESO 1 Group	1

Any event, Grade 3

Group	Value	95% CI
NY-ESO 1 Group	2

Any event, Grade 4

Group	Value	95% CI
NY-ESO 1 Group	0

Any event, Grade 5

Group	Value	95% CI
NY-ESO 1 Group	0

Number of Patients With Serious Adverse Events (SAEs) That Are Causally Related to Treatment Administration by Maximum Grade Secondary · During the study treatment period (maximum duration = 49 months).

A serious adverse event (SAE) is any untoward medical occurrence that results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect in the offspring of a study patient, is a grade 4 AE according to the Common Terminology Criteria for Adverse Events (CTCAE, v 4.0), in addition, in this study, Grade 3 or higher pIMDs will be considered as medically significant and will therefore be notified as SAE. No serious adverse events were reported during the study period that are causally

Group	Value	95% CI
NY-ESO 1 Group	0

Time to Treatment Failure (TTF) Secondary · From first treatment administration (i.e. at Week 0) until the last treatment administration (i.e. at Month 48)

Time to Treatment Failure (TTF) was defined as the time from first treatment until the date of the last treatment administration, for patients who discontinued the treatment prematurely, regardless of the reason for study treatment discontinuation. Patients who completed their full treatment phase or who were still on treatment at the time of analysis were censored on their last study treatment administration date..

Group	Value	95% CI
NY-ESO 1 Group	4.7	3.3 – 11.7

Progression-free Survival (PFS) Rate Secondary · From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)

Progression-free survival (PFS) was defined as the time from first treatment to either the date of first disease progression (PD) or the date of death (for whatever reason), whichever came first. Patients alive and without disease progression were censored at the date of the last visit/contact.

Group	Value	95% CI
NY-ESO 1 Group	2.8	2.8 – 2.9

Overall Survival (OS) Secondary · From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)

Overall survival (OS) was defined as the time from first treatment until death. Patients alive at the time of analysis were censored at the time of last visit/contact.

Group	Value	95% CI
NY-ESO 1 Group	NA	NA – NA

Number of Patients With Progression-free Survival Events Secondary · From first treatment administration (i.e. at Week 0) until the last tumor evaluation (i.e. at Month 49)

Progression-free survival was defined as the time from the date of registration of the patient to either the date of disease progression or the date of death (for whatever reason), whichever came first. Patients alive and without disease progression were censored at the date of their last tumor evaluation. PFS events included progressive disease (PD), death in absence of PD and events (Any event which was part of the natural course of the disease under study, was captured as an efficacy measure. Therefore it did not need to be reported as an SAE).

PD, Yes

Group	Value	95% CI
NY-ESO 1 Group	29

PD, No

Group	Value	95% CI
NY-ESO 1 Group	4

Death in absence of PD, Yes

Group	Value	95% CI
NY-ESO 1 Group	0

Death in absence of PD, No

Group	Value	95% CI
NY-ESO 1 Group	33

Events, Yes

Group	Value	95% CI
NY-ESO 1 Group	29

Events, No

Group	Value	95% CI
NY-ESO 1 Group	4

Summary of Deaths Related to Progressive Disease of Cancer Under Study Reported After the Study Treatment, in the Period of Long-term Follow-up for Survival Secondary · During the long-term Follow-Up period for progressive disease and survival [1 year after the study treatment end (at Month 49) or up to 5 years after the first study treatment administration, regardless of disease progression and study discontinuation.]

Summary of deaths included death, autopsy performed and cause of death. Progression of the tumor was recorded in the clinical assessments. Death due to progressive disease was to be recorded on a specific form in the case report form but not as a serious adverse event (SAE). However, if the investigator considered that there was a causal relationship between the administration of the treatment or protocol design/procedures and the disease progression, then this must be reported as an SAE.

Death, Yes

Group	Value	95% CI
NY-ESO 1 Group	8

Death, No

Group	Value	95% CI
NY-ESO 1 Group	25

Autopsy performed, Yes

Group	Value	95% CI
NY-ESO 1 Group	0

Autopsy performed, No

Group	Value	95% CI
NY-ESO 1 Group	6

Autopsy performed, Unknown

Group	Value	95% CI
NY-ESO 1 Group	2

Cause of death, Disease under study (melanoma)

Group	Value	95% CI
NY-ESO 1 Group	8

Adverse events — posted to ClinicalTrials.gov

Time frame: AEs and SAEs were collected during the study treatment period, i.e. from Month 0 to Month 49 (maximum treatment duration) in the overall population. All-Cause Mortality events were collected during the long-term Follow-Up period for progressive disease and survival [1 year after the study treatment end (at Month 49) or up to 5 years after the first study treatment administration, regardless of disease progression and study discontinuation.]. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

NY-ESO 1 Group

Serious: 3/33 (9%)

Deaths: 8/33

Serious adverse events (4 terms)

Reaction	System	NY-ESO 1 Group
Anaemia	Blood and lymphatic system disorders	—
Postoperative wound infection	Infections and infestations	—
Back pain	Musculoskeletal and connective tissue disorders	—
Uterine cyst	Reproductive system and breast disorders	—

Other adverse events (102 terms — click to expand)

Reaction	System	NY-ESO 1 Group
Injection site pain	General disorders	—
Fatigue	General disorders	—
Influenza like illness	General disorders	—
Pyrexia	General disorders	—
Headache	Nervous system disorders	—
Nausea	Gastrointestinal disorders	—
Asthenia	General disorders	—
Injection site erythema	General disorders	—
Injection site reaction	General disorders	—
Decreased appetite	Metabolism and nutrition disorders	—
Myalgia	Musculoskeletal and connective tissue disorders	—
Diarrhoea	Gastrointestinal disorders	—
Chills	General disorders	—
Pain	General disorders	—
Back pain	Musculoskeletal and connective tissue disorders	—
Lethargy	Nervous system disorders	—
Pruritus	Skin and subcutaneous tissue disorders	—
Injection site pruritus	General disorders	—
Malaise	General disorders	—
Oedema peripheral	General disorders	—
Sinusitis	Infections and infestations	—
Pain in extremity	Musculoskeletal and connective tissue disorders	—
Dizziness	Nervous system disorders	—
Paraesthesia	Nervous system disorders	—
Erythema	Skin and subcutaneous tissue disorders	—
Abdominal pain	Gastrointestinal disorders	—
Constipation	Gastrointestinal disorders	—
Vomiting	Gastrointestinal disorders	—
Injection site induration	General disorders	—
Injection site oedema	General disorders	—
Injection site swelling	General disorders	—
Hypersensitivity	Immune system disorders	—
Upper respiratory tract infection	Infections and infestations	—
Weight decreased	Investigations	—
Neck pain	Musculoskeletal and connective tissue disorders	—
Disturbance in attention	Nervous system disorders	—
Insomnia	Psychiatric disorders	—
Dry skin	Skin and subcutaneous tissue disorders	—
Hyperhidrosis	Skin and subcutaneous tissue disorders	—
Night sweats	Skin and subcutaneous tissue disorders	—

Most-reported serious reactions: Anaemia, Postoperative wound infection, Back pain, Uterine cyst.

Data from ClinicalTrials.gov NCT01213472 adverse events section.

Sponsor's own description

The purpose of this study is to investigate the safety, immunogenicity and clinical activity of GSK2241658A antigen-specific cancer immunotherapeutic (ASCI) for the treatment of patients with non-operable and progressing metastatic cutaneous melanoma.

Publications & conference data

6 peer-reviewed publications reference this trial (live from Europe PMC):

1. Cancer/testis antigens and urological malignancies.
   Kulkarni P, Shiraishi T, Rajagopalan K, Kim R, et al · · 2012 · cited 50× · PMID 22710665 · DOI 10.1038/nrurol.2012.117
2. Cancer testis antigen and immunotherapy.
   Krishnadas DK, Bai F, Lucas KG. · · 2013 · cited 43× · PMID 27471684 · DOI 10.2147/itt.s35570
3. Multicenter, real-life experience with checkpoint inhibitors and targeted therapy agents in advanced melanoma patients in Switzerland.
   Mangana J, Cheng PF, Kaufmann C, Amann VC, et al · · 2017 · cited 20× · PMID 28509765 · DOI 10.1097/cmr.0000000000000359
4. Crosstalk between Stress Granules, Exosomes, Tumour Antigens, and Immune Cells: Significance for Cancer Immunity.
   Kothandan VK, Kothandan S, Kim DH, Byun Y, et al · · 2020 · cited 9× · PMID 32276342 · DOI 10.3390/vaccines8020172
5. Identification of pan-cancer/testis genes and validation of therapeutic targeting in triple-negative breast cancer: Lin28a-based and Siglece-based vaccination induces antitumor immunity and inhibits metastasis.
   Carter JA, Matta B, Battaglia J, Somerville C, et al · · 2023 · cited 5× · PMID 38135347 · DOI 10.1136/jitc-2023-007935
6. Immunotherapeutics in metastatic cancer management.
   Shukla M, Shri P, Mahobiya SK, Vishwakarma RK. · · 2025 · PMID 41239147 · DOI 10.1007/s12672-025-03561-5