Informations générales (source: ClinicalTrials.gov)
A Phase I, Open-label, Dose Finding Study to Assess the Safety, Tolerability, PK, and Preliminary Efficacy of OBT076, a CD205-directed ADC, in Recurrent and/or Metastatic CD205+ Solid Tumors
Interventional
Phase 1
Oxford BioTherapeutics Ltd (Voir sur ClinicalTrials)
juillet 2019
décembre 2027
29 juin 2024
The purpose of this study is to evaluate OBT076, which is a drug that combines an
antibody with an anti-cancer drug. This class of drugs are called Antibody-Drug
Conjugates (ADC). Antibodies are normally produced in the human body by the immune system
to fight infections but can be designed to target cancer cells and deliver an anti-cancer
drug. OBT076 is composed of an antibody that targets the CD205 protein on cancer cells
and delivers an anti-cancer drug which can kill them. OBT076 is an "Investigational
Drug", which means that it is still being studied and has not yet been approved by the US
Food and Drug Administration (FDA), the European Medicines Agency (EMA) or any other
regulatory authorities to be prescribed by doctors for the treatment of metastatic or
recurrent solid tumors. The use of OBT076 in this study is investigational.
This is a Phase I research study designed to look at several dose levels of the study
drug to find the highest dose level that is safe and well-tolerated (does not cause
unacceptable side effects), and to examine the effects of the study drug in a small group
of research participants. The study will also look at the effectiveness of OBT076 as an
anti-cancer therapy. Once the optimal dose is determined and safety is assessed,
additional research participants will be treated at the optimal dose level to further
evaluate safety and effectiveness.
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Sophie POSTEL-VINAY | 17/05/2024 13:18:27 | Contacter | ||
| Les établissements d'Île-de-France dont les données sont issues de ClinicalTrials.gov Origine et niveau de fiabilité des données | |||||
| AP-HP - Hôpital Saint Antoine | Clinical Trials | Contact (sur clinicalTrials) | |||
| GH PARIS SITE SAINT JOSEPH | Clinical Trials | Contact (sur clinicalTrials) | |||
| 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 Eugène Marquis - Rennes - France | Clinical Trials | Contact (sur clinicalTrials) | |||
| Hopital Saint Louis - Paris - France | Clinical Trials | Contact (sur clinicalTrials) | |||
| ICANS - Institut de cancérologie Strasbourg - Strasbourg - France | Clinical Trials | Contact (sur clinicalTrials) | |||
| Institut Gustave Roussy - IGR - Villejuif - France | Contact (sur clinicalTrials) | ||||
| Institut Paoli Calmettes - Marseille - France | Contact (sur clinicalTrials) | ||||
Critères
Tous
Inclusion Criteria:
1. Subject is ≥ 18 years of age (at the time of signing the ICF) with non-curative
recurrent and/or metastatic solid tumors for which a standard therapy is not
available or is no longer effective.
2. Subject has histologically and/or cytologically confirmed solid tumors.
3. Subject with Breast cancer:
1. Subject with hormone-receptor positive (as per local laboratory) recurrent
locally advanced or metastatic breast cancer, regardless of HER2 status, must
have received at least two prior lines of endocrine therapy in the adjuvant or
metastatic setting, either as monotherapy or in combination with targeted
therapy
2. Subject with recurrent locally advanced or metastatic non-curative HER2
negative breast cancer (based on most recently analyzed biopsy), HER2 status is
defined as per ASCO-CAP guidelines as negative, if in situ hybridization test
or IHC status is 0, 1+, or 2+.
3. Subject with triple negative breast cancer are eligible after at least one
prior line of cytotoxic chemotherapy in the metastatic setting.
4. Subject with prior adjuvant or neoadjuvant chemotherapy allowed.
4. Subject has received a maximum of two prior lines of cytotoxic chemotherapy in the
metastatic setting. Subject who received three up to five prior lines of cytotoxic
chemotherapy in the metastatic setting are eligible, if the last administration of
cytotoxic chemotherapy was at least 12 weeks prior to Cycle 1 Day 1
5. Subject has tumor that is positive for CD205 antigen by IHC staining
6. Subject has an ECOG performance status of 0-1.
7. Subject has radiological documented measurable disease (i.e., at least 1 measurable
lesion as per RECIST Version 1.1).
8. Subject has adequate organ function
9. Subject has adequate bone marrow function
10. Subject understands and voluntarily signs an ICD prior to any study-related
assessments/procedures are conducted.
11. Subject is able to adhere to the study visit schedule and other protocol
requirements.
12. Subject who is a female of childbearing potential (defined as a sexually mature
women, has not undergone hysterectomy (the surgical removal of the uterus) or
bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been
naturally postmenopausal for at least 12 consecutive months and is using any
adequate form of birth control must:
1. Have a negative pregnancy test within 1 week before first dose of study drug.
2. Use highly effective method(s) of birth control consistently and correctly
during the study and for at least 4 months after the last dose of study drug.
3. Agree to not donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for at least 4 months after the last dose of
study.
4. Agree to no plan to breastfeed and no plan to become pregnant during the study
and for at least 4 months after the last dose of study drug.
13. Subject who is a sexually active male must agree to use a condom, not to donate
sperm and have no plans to father a child during the study and for at least 4 months
after the last dose of study drug.
1. Subject is ≥ 18 years of age (at the time of signing the ICF) with non-curative
recurrent and/or metastatic solid tumors for which a standard therapy is not
available or is no longer effective.
2. Subject has histologically and/or cytologically confirmed solid tumors.
3. Subject with Breast cancer:
1. Subject with hormone-receptor positive (as per local laboratory) recurrent
locally advanced or metastatic breast cancer, regardless of HER2 status, must
have received at least two prior lines of endocrine therapy in the adjuvant or
metastatic setting, either as monotherapy or in combination with targeted
therapy
2. Subject with recurrent locally advanced or metastatic non-curative HER2
negative breast cancer (based on most recently analyzed biopsy), HER2 status is
defined as per ASCO-CAP guidelines as negative, if in situ hybridization test
or IHC status is 0, 1+, or 2+.
3. Subject with triple negative breast cancer are eligible after at least one
prior line of cytotoxic chemotherapy in the metastatic setting.
4. Subject with prior adjuvant or neoadjuvant chemotherapy allowed.
4. Subject has received a maximum of two prior lines of cytotoxic chemotherapy in the
metastatic setting. Subject who received three up to five prior lines of cytotoxic
chemotherapy in the metastatic setting are eligible, if the last administration of
cytotoxic chemotherapy was at least 12 weeks prior to Cycle 1 Day 1
5. Subject has tumor that is positive for CD205 antigen by IHC staining
6. Subject has an ECOG performance status of 0-1.
7. Subject has radiological documented measurable disease (i.e., at least 1 measurable
lesion as per RECIST Version 1.1).
8. Subject has adequate organ function
9. Subject has adequate bone marrow function
10. Subject understands and voluntarily signs an ICD prior to any study-related
assessments/procedures are conducted.
11. Subject is able to adhere to the study visit schedule and other protocol
requirements.
12. Subject who is a female of childbearing potential (defined as a sexually mature
women, has not undergone hysterectomy (the surgical removal of the uterus) or
bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been
naturally postmenopausal for at least 12 consecutive months and is using any
adequate form of birth control must:
1. Have a negative pregnancy test within 1 week before first dose of study drug.
2. Use highly effective method(s) of birth control consistently and correctly
during the study and for at least 4 months after the last dose of study drug.
3. Agree to not donate eggs (ova, oocytes) for the purposes of assisted
reproduction during the study and for at least 4 months after the last dose of
study.
4. Agree to no plan to breastfeed and no plan to become pregnant during the study
and for at least 4 months after the last dose of study drug.
13. Subject who is a sexually active male must agree to use a condom, not to donate
sperm and have no plans to father a child during the study and for at least 4 months
after the last dose of study drug.
1. Subject has received any chemotherapy within 28 days prior to Cycle 1 Day 1.
2. Subject has received any other systemic anticancer therapy within 28 days or 5
half-lives of Cycle 1 Day 1.
3. Subject has symptomatic visceral crisis requiring chemotherapy per Investigator
judgment for non TNBC.
4. Subject with colorectal cancer and pancreatic cancer are not eligible for the study.
5. Subject with peritoneal involvement, i.e., peritoneal carcinomatosis, are not
eligible for the study.
6. Subject has not recovered from the acute toxic effects (CTCAE grade ≤ 1) of prior
anticancer therapy, radiation, or major surgery/significant trauma (except alopecia
or other toxicities not considered a safety risk for the subject at the
Investigator's discretion).
7. Subject has had major surgery within 14 days prior to starting study treatment or
has not recovered from major side effects.
8. Subject has had radiotherapy ≤ 4 weeks prior to starting study drug.
9. Subject has a history of, or current symptomatic brain metastasis.
10. Subject has any other malignancy within 5 years prior to randomization
11. Subject has a known or suspected hypersensitivity or other contraindication to any
excipients used in the manufacture of OBT076.
12. Subject has significant medical condition, laboratory abnormality, or psychiatric
illness that would, in the Investigator's judgment, contraindicate patient
participation in the study (e.g., history of thromboembolic event, cardiac
dysfunction, chronic pancreatitis, chronic active hepatitis)
13. Subject has severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine <7
days before Cycle 1 Day 1
14. Subject has any condition that confounds the ability to interpret data from the
study.
15. Subject is lactating or breastfeeding.
16. Subject has a past medical history of or ongoing clinically relevant interstitial
lung disease, drug-induced pneumonitis or severe/very severe COPD.
17. Subject has active or chronic corneal disorder or Sjogren's syndrome.
18. Subject has any ongoing skin disorders not controlled by specific treatment.
19. Subject has significant active cardiac disease within the previous 6 months
including unstable angina or angina requiring surgical or medical intervention,
significant cardiac arrhythmia, or NYHA class 3 or 4 congestive heart failure, or
patients with QTc interval >470ms at screening.
20. Subject has a known history or current diagnosis of HIV infection, unless on triple
antiviral treatment with undetectable viral load.
21. Subject who is female of childbearing potential
22. Subject who is unable or unwilling to take folic acid or vitamin B12
supplementation.
23. Subject with a history of allogeneic organ transplant.
24. Subject with grade 3 or 4 immune-related adverse reactions during any prior line of
checkpoint inhibitor containing therapy. Patients with immune-related thyroiditis
controlled with substitution, or prior asymptomatic lipase increases are eligible
for the study.
25. Subject with active autoimmune disease or history of autoimmune disease that
required systemic treatment within 3 years of the start of study treatment.