Informations générales (source: ClinicalTrials.gov)
Phase 1/2 Dose Escalation and Cohort Expansion Study Evaluating MCLA-158 (Petosemtamab) as Single Agent or in Combination in Advanced Solid Tumors
Interventional
Phase 1/Phase 2
Merus N.V. (Voir sur ClinicalTrials)
mai 2018
novembre 2027
13 juillet 2024
This is a Phase 1/2 open-label, multi-center, multi-national study with an initial dose
escalation part to determine the recommended Phase II dose (RP2D) of MCLA-158 single
agent in patients with mCRC.
The dose escalation part has been completed and the RP2D will be further evaluated in an
expansion part of the study. Cohorts of selected solid tumor indications for which there
is evidence of EGFR dependency and potential sensitivity to EGFR inhibition will be
evaluated including head and neck cancer and metastatic colorectal cancer (mCRC).
The study will further assess the safety, tolerability, PK, PD, immunogenicity, and
anti-tumor activity of MCLA-158.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT CURIE | 04/12/2024 12:44:17 | Contact (sur clinicalTrials) | |||
| CLCC INSTITUT GUSTAVE ROUSSY | Antoine HOLLEBECQUE | 31/05/2024 10:04:36 | Contacter | ||
| Les établissements sans correspondance certaine dans le répertoire FINESS dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| Centre Antoine Lacassagne - Nice - France | Ariane Guillemart | Contact (sur clinicalTrials) | |||
| Centre Henri Becquerel - Rouen - France | Amelie Poullain | Contact (sur clinicalTrials) | |||
| Centre Leon Berard - Lyon - France | Martin Porret | Contact (sur clinicalTrials) | |||
| Hopital La Timone - Marseille - France | Leyla Ameur, MD | Contact (sur clinicalTrials) | |||
| Hopital Saint Andre, CHU Bordeaux - Bordeaux - France | Delphine Padenon | Contact (sur clinicalTrials) | |||
| Institut Gustave Roussy - Paris - France | Sandrine Lancereau | Contact (sur clinicalTrials) | |||
| Institut Régional du Cancer de Montpellier - Montpellier - France | Justine Rochet | Contact (sur clinicalTrials) | |||
Critères
Tous
Inclusion Criteria:
- Histologically or cytologically confirmed solid tumors with evidence of metastatic
or locally advanced disease not amenable to standard therapy with curative intent.
- A baseline fresh tumor sample (FFPE) from a metastatic or primary site.
- Amenable for biopsy (if safe/feasible).
- Measurable disease as defined by RECIST version 1.1 by radiologic methods.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 12 weeks, as per investigator.
- Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple
gated acquisition scan (MUGA).
- Adequate organ function
- Expansion cohorts: patients with locally advanced unresectable or metastatic disease
for the following indications:
SINGLE AGENT:
- SECOND-/THIRD-LINE HNSCC PATIENTS (cohort closed to enrolment): patients who have
progressed on or after, or are intolerant to, anti-PD-(L)1 therapy and platinum
therapy as monotherapy or in combination with other agents and no previous exposure
to EGFR inhibitors. Patients treated with platinum-containing therapy only in the
adjuvant setting, or in the context of multimodal therapy for locally advanced
disease should have disease progression within 6 months of the last dose of platinum
containing therapy. Patients with no more than 2 prior lines of treatment in
recurrent or metastatic disease.
- Human papilloma virus (HPV) status determined by p16 immunohistochemistry (IHC)
or molecular HPV test for all oropharyngeal tumors should be reported when
available.
- The eligible HNSCC primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
- GEA with histologically confirmed EGFR amplification (fluorescence in situ
hybridization [FISH] score EGFR/chromosome 7 (CEP7) ratio ≥2.0, or tumor next
generation sequencing [NGS] EGFR copy ≥8, or cfDNA ≥2.5, or EGFR IHC H-score ≥200).
Cohort closed to enrolment.
- Patients with other indications must have been previously treated with 1 or 2 lines
of the standard approved therapy (when applicable) in the locally
advanced/unresectable or metastatic setting. Other indications may considered such
as malignant salivary gland tumors. Cohort closed to enrolment.
COMBINATION:
- FIRST-LINE HNSCC (cohort closed to enrolment): patients eligible to receive
pembrolizumab as first-line monotherapy with tumors expressing programmed cell death
protein ligand 1 (PD-L1), combined positive score (CPS) ≥1, as determined by a Food
and Drug Administration (FDA) approved test in the US, or by an approved equivalent
test in other countries; patients should not have previous systemic therapy
administered in the recurrent or metastatic setting, although previous systemic
therapy as part of multimodal treatment for locally advanced disease is allowed if
ended ≥6 months prior to signing the ICF. The eligible HNSCC primary tumor locations
are oropharynx, oral cavity, hypopharynx, and larynx. Previous treatments with anti
PD-(L)1 or anti-EGFR therapies are not allowed.
- 2L mCRC (cohort open to enrolment): Patients should have been previously diagnosed
with histologically or cytologically confirmed unresectable or metastatic
adenocarcinoma of the colon or rectum. Patients must be RAS/RAF WT as determined
using NGS on tumor tissue (primary or metastatic) or other appropriate tumor tissue
based assay, to be confirmed by the sponsor. Patients must be naive to prior
anti-EGFR therapy. Radiographically confirmed disease progression must have occurred
during or within 6 months of prior 1L chemotherapy.
- Cohort to be treated with petosemtamab and FOLFIRI: patients should have had
only 1 prior chemotherapy regimen for the metastatic setting, consisting of 1L
fluoropyrimidine-oxaliplatin-based chemotherapy ± bevacizumab. Note:
FOLFOX-based adjuvant treatment would be considered front-line if PD occurred
within 6 months of completion of adjuvant therapy.
- Histologically or cytologically confirmed solid tumors with evidence of metastatic
or locally advanced disease not amenable to standard therapy with curative intent.
- A baseline fresh tumor sample (FFPE) from a metastatic or primary site.
- Amenable for biopsy (if safe/feasible).
- Measurable disease as defined by RECIST version 1.1 by radiologic methods.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy ≥ 12 weeks, as per investigator.
- Left ventricular ejection fraction (LVEF) ≥ 50% by echocardiogram (ECHO) or multiple
gated acquisition scan (MUGA).
- Adequate organ function
- Expansion cohorts: patients with locally advanced unresectable or metastatic disease
for the following indications:
SINGLE AGENT:
- SECOND-/THIRD-LINE HNSCC PATIENTS (cohort closed to enrolment): patients who have
progressed on or after, or are intolerant to, anti-PD-(L)1 therapy and platinum
therapy as monotherapy or in combination with other agents and no previous exposure
to EGFR inhibitors. Patients treated with platinum-containing therapy only in the
adjuvant setting, or in the context of multimodal therapy for locally advanced
disease should have disease progression within 6 months of the last dose of platinum
containing therapy. Patients with no more than 2 prior lines of treatment in
recurrent or metastatic disease.
- Human papilloma virus (HPV) status determined by p16 immunohistochemistry (IHC)
or molecular HPV test for all oropharyngeal tumors should be reported when
available.
- The eligible HNSCC primary tumor locations are oropharynx, oral cavity,
hypopharynx, and larynx.
- GEA with histologically confirmed EGFR amplification (fluorescence in situ
hybridization [FISH] score EGFR/chromosome 7 (CEP7) ratio ≥2.0, or tumor next
generation sequencing [NGS] EGFR copy ≥8, or cfDNA ≥2.5, or EGFR IHC H-score ≥200).
Cohort closed to enrolment.
- Patients with other indications must have been previously treated with 1 or 2 lines
of the standard approved therapy (when applicable) in the locally
advanced/unresectable or metastatic setting. Other indications may considered such
as malignant salivary gland tumors. Cohort closed to enrolment.
COMBINATION:
- FIRST-LINE HNSCC (cohort closed to enrolment): patients eligible to receive
pembrolizumab as first-line monotherapy with tumors expressing programmed cell death
protein ligand 1 (PD-L1), combined positive score (CPS) ≥1, as determined by a Food
and Drug Administration (FDA) approved test in the US, or by an approved equivalent
test in other countries; patients should not have previous systemic therapy
administered in the recurrent or metastatic setting, although previous systemic
therapy as part of multimodal treatment for locally advanced disease is allowed if
ended ≥6 months prior to signing the ICF. The eligible HNSCC primary tumor locations
are oropharynx, oral cavity, hypopharynx, and larynx. Previous treatments with anti
PD-(L)1 or anti-EGFR therapies are not allowed.
- 2L mCRC (cohort open to enrolment): Patients should have been previously diagnosed
with histologically or cytologically confirmed unresectable or metastatic
adenocarcinoma of the colon or rectum. Patients must be RAS/RAF WT as determined
using NGS on tumor tissue (primary or metastatic) or other appropriate tumor tissue
based assay, to be confirmed by the sponsor. Patients must be naive to prior
anti-EGFR therapy. Radiographically confirmed disease progression must have occurred
during or within 6 months of prior 1L chemotherapy.
- Cohort to be treated with petosemtamab and FOLFIRI: patients should have had
only 1 prior chemotherapy regimen for the metastatic setting, consisting of 1L
fluoropyrimidine-oxaliplatin-based chemotherapy ± bevacizumab. Note:
FOLFOX-based adjuvant treatment would be considered front-line if PD occurred
within 6 months of completion of adjuvant therapy.
- Central nervous system metastases that are untreated or symptomatic, or require
radiation, surgery, or continued steroid therapy to control symptoms within 14 days
of study entry.
- Known leptomeningeal involvement.
- Participation in another clinical trial or treatment with any investigational drug
within 4 weeks prior to study entry.
- Any systemic anticancer therapy within 4 weeks or 5 half-lives whichever is shorter
of the first dose of study treatment. For cytotoxic agents that have major delayed
toxicity ( e.g. mitomycin C,nitrosoureas), or anticancer immunotherapies, a washout
period of 6 weeks is required.
- Requirement for immunosuppressive medication (e.g. methotrexate, cyclophosphamide)
- Major surgery or radiotherapy within 3 weeks of the first dose of study treatment.
Patients who received prior radiotherapy to ≥25% of bone marrow are not eligible,
irrespective of when it was received.
- Persistent grade >1 clinically significant toxicities related to prior
antineoplastic therapies (except for alopecia); stable sensory neuropathy ≤ grade 2
NCI-CTCAE v4.03 is allowed.
- History of hypersensitivity reaction to any of the excipients of petosemtamab, human
proteins or any non-IMP treatment required for this study.
- Uncontrolled hypertension (systolic blood pressure [BP] > 150 mmHg and/or diastolic
BP > 100 mmHg) with appropriate treatment or unstable angina.
- History of congestive heart failure of Class II-IV New York Heart Association (NYHA)
criteria, or serious cardiac arrhythmia requiring treatment (except atrial
fibrillation, paroxysmal supraventricular tachycardia).
- History of myocardial infarction within 6 months of study entry.
- History of prior malignancies with the exception of excised cervical intraepithelial
neoplasia or nonmelanoma skin cancer, or curatively treated cancer deemed at low
risk for recurrence with no evidence of disease for 3 years.
- Current dyspnea at rest of any origin, or other diseases requiring continuous oxygen
therapy.
- Patients with a history of interstitial lung disease (e.g., pneumonitis or pulmonary
fibrosis) or evidence of ILD on baseline chest computerized tomography (CT) scan.
- Current serious illness or medical conditions including, but not limited to
uncontrolled active infection,clinically significant pulmonary, metabolic or
psychiatric disorders.
- Patients with known infectious diseases:
- Active hepatitis B infection ((hepatitis B surface antigen [HBsAg] positive)
without receiving antiviral treatment. Note: Patients who are HBsAg positive
must receive antiviral treatment with lamivudine, tenofovir, entecavir, or
other antiviral agents, starting at least ≥7 days before the initiation of the
study treatment. Patients with antecedents of hepatitis B (e.g., anti-hepatitis
B core (anti-HBc) positive, HBsAg and hepatitis B virus [HBV] DNA negative) are
eligible.
- Positive test for hepatitis C ribonucleic acid (HCV) RNA). Note: Patients in
whom HCV infection resolved spontaneously (i.e., positive HCV antibodies
without detectable HCV -RNA), or who achieved a sustained response after
antiviral treatment and show absence of detectable HCV RNA ≥6 months (with the
use of interferon [IFN]-free regimens) or ≥ 12 months (with t the use of
IFN-based regimens) after cessation of antiviral treatment, are eligible.
- Pregnant or breastfeeding patients; patients of childbearing potential must use
highly effective contraception methods prior to study entry, for the duration of
study participation, and for 6 months after the last dose of MCLA-158.