Informations générales (source: ClinicalTrials.gov)
A Phase 1/2 Randomized Multi-Cohort Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Clinical Activity of Mocertatug Rezetecan in Combination With Anti-Cancer Agents in Participants With Advanced Solid Tumors
Interventional
Phase 1/Phase 2
GlaxoSmithKline (Voir sur ClinicalTrials)
mars 2025
octobre 2028
04 octobre 2026
Advanced solid tumors are cancers that have spread to other parts of the body. While many
treatments exist, most people become resistant to them, and the cancer returns.
Researchers are developing new treatments that combine different medicines for those who
do not respond to single medicine. This study is looking at how safe and tolerable
Mocertatug Rezetecan (Mo-Rez) is, how the body handles it, and how well it works when
used with other cancer medicines. The study will include participants with advanced solid
tumors who have either not responded to standard treatments or cannot tolerate them or
have no available effective treatment.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Yohann LORIOT | 21/09/2026 17:50:02 | Contacter | ||
Critères
Tous
- Participants must be 18 years of age inclusive or older, at the time of signing the
informed consent, or the legal age of consent in the jurisdiction in which the study
is taking place.
- Participant capable of giving signed informed consent including compliance with the
requirements and restrictions listed in the Informed consent form (ICF) and in this
protocol.
- Participants with pathologically confirmed advanced solid tumor specific for study
Module (key local diagnostic molecular and/or immunophenotyping testing
results/tumor cell phenotype results for confirmed diagnosis should be provided)
with no more than 4 lines of prior systemic therapies. Please note:
1. Adjuvant +/- neoadjuvant considered one line of therapy
2. Maintenance therapy will be considered as part of the preceding line of therapy
(i.e., not counted independently)
3. Unplanned addition or switching to a new drug in a different class is
considered a separate line of therapy. If an agent in a regimen is switched to
another agent in the same class due to toxicity or intolerance (e.g.
hypersensitivity reaction) this is considered part of the same line (i.e. not
counted independently).
- Requirements for tumor tissue samples: Archival or fresh tumor tissue is required
for retrospective central assessment of B7H4 expression by immunohistochemistry
(IHC) and other biomarker analysis. The archival tumor tissue should be from the
most recent procedure (ideally obtained after the last anti-cancer treatment). If an
archival tissue is not available a new biopsy should be performed, and the newly
obtained tissue provided.
- Participants have at least one target lesion as assessed per RECIST 1.1. A target
lesion is defined as a measurable lesion that has not undergone locoregional
treatment such as irradiation or that has unequivocal progression following
locoregional treatment, with the longest diameter of ≥ 10 millimeter (mm) at
Baseline (for lymph node lesions, the short axis should be ≥ 15 mm).
- Participants have a life expectancy of at least 12 weeks per investigator assessment
based on disease burden and extent of supportive care needed.
Inclusion criteria of participants under arm Module 1 (Mo-Rez +Dostarlimab) Endometrial
Cancer Part 1A:
a. Participants with histologically documented, advanced (metastatic and/or unresectable)
or recurrent endometrial cancer who have failed in adequate standard treatments, do not
have effective standard treatment or are intolerant to standard of care, and who are not
candidates for further curative external radiotherapy or brachytherapy.
Inclusion criteria of participants under arm Module 1 (Mo-Rez +Dostarlimab) Endometrial
Cancer Part 1B:
1. Diagnosis of endometrial cancer with confirmed mismatch repair proficient (MMRp) or
microsatellites stable (MSS) tumor status by local test.
2. Participants who have progressed on or are intolerant to at least 1 line of standard
prior systemic therapy (including neoadjuvant or adjuvant as prior line), and who
are not candidates for curative external radiotherapy or brachytherapy. Maintenance
therapy will be considered part of the preceding line of therapy (i.e, not counted
independently).
Inclusion criteria of participants under arm Module 2 (Mo-Rez +/- Bevacizumab) Ovarian
Cancer Part 2A:
a. Participants with histologically or cytologically confirmed advanced epithelial
ovarian cancer/fallopian tube/peritoneal cancer (any epithelial histology - mucinous,
clear cell, carcinosarcoma, high/low grade serous, endometrioid) who have failed in
adequate standard treatments, do not have effective standard treatment or are intolerant
to standard of care.
Inclusion criteria of participants under arm Module 2 (GSK5733584 +/- Bevacizumab)
Ovarian Cancer Part 2B:
1. Participants whose advanced ovarian cancer/fallopian tube/peritoneal cancer has
relapsed more than 6 months from the last dose of platinum before enrollment, i.e.,
platinum sensitive.
2. Participants who have progressed on or are intolerant to at least 1 line of standard
prior lines of chemotherapy and are not candidates for second cytoreductive surgery.
- Participants willing to use adequate contraception.
Female participants:
A female participant is eligible to participate if she is not pregnant or breastfeeding,
and one of the following conditions applies:
- Is a Woman of non-childbearing potential (WONCBP) OR
- Is a Woman of childbearing potential (WOCBP) and using a contraceptive method that
is highly effective.
- A WOCBP must have a negative highly sensitive pregnancy test (urine or serum as
required by local regulations) within 24 hours before the first dose of study
intervention
- Has an ECOG performance status of 0 to 1.
- Participants with normal organ and bone marrow function.
Exclusion Criteria:
- Has a second malignancy (except disease under study) that has progressed or required
active treatment within the past 24 months except for basal cell or squamous cell
carcinomas of the skin or in-situ carcinomas [e.g., breast, cervix, bladder] that
have been resected with no evidence of metastatic disease.
- Has had any major surgery within 28 days prior to enrolment.
- Has any history of prior allogenic or autologous bone marrow transplant or other
solid organ transplant.
- Has known sensitivity to study intervention components, Mo-Rez (antibody-drug
conjugate, antibody, free cytotoxin GSK5757810A) and combination partner, or its
excipients or other allergy that, in the opinion of the investigator,
contraindicates participation in the study.
- Has any following cardiological examination abnormality:
1. history in prior year of clinically significant or uncontrolled cardiac
disease, acute myocardial infarction, NYHA Class III or IV congestive heart
failure or clinically significant arrhythmia not controlled by standard of care
therapy.
2. Corrected QT Interval (QTcF) >450 millisecond (msec) or QTcF >480 msec for
participants with bundle branch block
- Has untreated brain or CNS metastases or brain/CNS metastases rapidly progressing
requiring urgent medical intervention.
- Any evidence of current interstitial lung disease (ILD) or pneumonitis or a prior
history of ILD or non-infectious pneumonitis.
- Has a history of autoimmune disease that has required systemic treatments in the 2
years prior to screening (i.e., with use of disease modifying agents,
corticosteroids, or immunosuppressive drugs). Replacement therapy is not considered
a form of systemic therapy (e.g., thyroid hormone for autoimmune thyroiditis or
insulin is not exclusionary).
- Clinically significant bleeding symptoms, significant bleeding tendency, or bleeding
tumors within 1 month prior to the first dose of study treatment.
- Serious or poorly controlled hypertension, including history of hypertensive crisis,
hypertensive encephalopathy; adjustment of antihypertensive medications due to poor
blood pressure control within 2 weeks prior to the first dose of study treatment;
- Has any active renal condition (e.g., infection, requirement for dialysis, or any
other active significant renal condition or dehydrated condition that could affect
the participant's safety). Note: renal obstruction successfully managed by stenting
is permitted.
- Has any serious and/or unstable medical condition (such as clinical symptoms of
intestinal obstruction) or psychiatric disorder or other condition(s) (including
laboratory assessment abnormalities) that could interfere with the participant's
safety, obtainment of informed consent, or compliance to the study procedures.
- Participants with known history of Human immunodeficiency virus (HIV).
Exclusion criteria of participants under arm Module 1 (Mo-Rez +Dostarlimab) Endometrial
Cancer:
1. Has mesenchymal tumor of the uterus (uterine sarcoma).
2. Has experienced symptomatic pericarditis of any etiology within 6 months of study
treatment or any of the following with prior immunotherapy: any imAE ≥ Grade 3,
immune-mediated severe neurologic events of any-grade (e.g., myasthenic
syndrome/myasthenia gravis, encephalitis Guillain-Barré Syndrome, or transverse
myelitis), exfoliative dermatitis of any grade (SJS, TEN, or DRESS syndrome), or
myocarditis of any grade.
Exclusion criteria of participants under arm Module 2 (Mo-Rez +/-Bevacizumab) Ovarian
Cancer:
1. Participants with wound healing complications or incompletely healed wounds.
2. Participants with history or evidence of gastrointestinal perforation,
tracheoesophageal fistula, or any grade 4 fistula; participants with
gastrointestinal fistula, visceral fistula, or abdominal abscess within 6 months
prior to the first dose, participants with history of osteonecrosis of the jaw.
3. Participants who have evidence of recto-sigmoid involvement by pelvic examination or
bowel involvement on CT scan or clinical symptoms of bowel obstruction.
4. Participants with congenital bleeding diathesis, acquired coagulopathy, recent
pulmonary haemorrhage/ haemoptysis (> 2.5 mL of red blood or ½ teaspoon) within the
last 3 months. Participants receiving treatment for thromboembolism are permitted as
long as they have been on a stable dose of anticoagulation for at least 1 month.
5. Participant has history of congestive heart failure (CHF) or baseline LVEF <50% or
institutional lower limits of normal.
6. Participant with history of nephrotic syndrome or grade 3 proteinuria. Participants
has proteinuria as demonstrated by urine dipstick for proteinuria ≥2 (participants
discovered to have ≥2 proteinuria on dipstick at baseline should undergo 24-hour
urine collection and must demonstrate ≤1 g of protein in 24 hours to be eligible).
- Has an Alanine transaminase (ALT) value >2.5x Upper Limit of Normal (ULN) and
for participants with documented liver metastases/tumor infiltration has an ALT
value >5x ULN.
- Has a total bilirubin value >1.5x ULN.
- Has documented presence of HBsAg and/or HBcAb, or HBsAb (except for presence of
HBsAb attributable to previous vaccination) at screening or within 3 months
prior to the first dose of study intervention.
- Has a positive HCV antibody test result at screening or within 3 months prior
to the first dose of study intervention.
- Has received prior therapy with topoisomerase-1 inhibitors or ADC with
topoisomerase-1 inhibitor warhead, or B7H4 targeted therapy.
- Has received treatment with any cytotoxic chemotherapy drugs or other
anti-tumor drugs (including endocrine therapy, molecular targeted therapy,
immunotherapy, biotherapy, and investigational drug) within 30 days or 5
half-lives, whichever is shorter of a medicinal product prior to the first dose
of study drug; or need to continue these drugs during the study.
- Use of inhibitors of P-gp, breast cancer resistance protein (BCRP) or
OATP1B1/1B3 within 7 days prior to the first dose of study drug. P-gp inducers
should be discontinued for at least 14 days before the start of the study.
- Have received locoregional radiation therapy within 2 weeks prior to the first
dose of study drug; more than 30% of bone marrow irradiation or wide-field
radiation therapy within 4 weeks prior to the first dose of study treatment.
- Has serious infections within 4 weeks prior to the first dose, including but
not limited to infectious complications, bacteremia, severe pneumonia treated
with intravenous antibiotics for ≥2 weeks.