Study of AG-270 in Participants With Advanced Solid Tumors or Lymphoma With MTAP Loss

Stopped early · Phase 1

Conditions studied: Advanced Solid Tumors, Lymphoma

In brief

This study will evaluate the safety, pharmacokinetics, pharmacodynamics, and clinical activity of AG-270 in participants with advanced solid tumors or lymphoma with homozygous MTAP deletion.

Key facts

Study ID

NCT03435250

Run by

Institut de Recherches Internationales Servier

People needed

123

Starts

2018-03-04

Expected to finish

2023-04-20

Last updated by the study team

2024-07-25

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• AG-270 Monotherapy
• Be ≥18 years of age;
• Have a histologically confirmed diagnosis of an advanced solid tumor or lymphoma that has progressed in spite of at least one prior line of treatment, and for which additional effective standard therapy is not available. For this study, effective standard therapy is defined as treatment that has been shown to be curative and/or to prolong survival. In addition, participants who are considered to not be candidates for standard therapy or who decline standard therapy are eligible for this study; in such cases, documentation of the reason for omitting or declining a standard therapy is required;
• Have evidence of homozygous loss of cyclin-dependent kinase inhibitor 2A (CDKN2A) and/or MTAP in the participant's tumor tissue;
• Have disease that can be clinically evaluated for improvement or progression. In the dose-expansion phase of the study arm, participants must have disease that is measurable, as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 criteria for solid tumors (Eisenhauer et al, 2009) or the Lugano criteria for lymphoma (Cheson et al, 2014);
• Have an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of ≤2;
• Have a hemoglobin ≥9.0 grams per deciliter (g/dL) without red blood cell transfusion for ≥1 month;
• Have an absolute neutrophil count (ANC) ≥1.0 × 10\^9/liter (L);
• Have a platelet count ≥75 × 10\^9/L;
• Have a serum total bilirubin ≤1.5 × upper limit of normal (ULN);
• Have an alanine aminotransferase (ALT) ≤3.0 × ULN. (Note: There are no specific requirements for aspartate aminotransferase (AST) or Alkaline phosphatase [ALP]);
• Have a serum creatinine ≤1.5 × ULN;
• Be fully recovered from major surgery and from the acute toxic effects of prior chemotherapy and radiotherapy. Residual chronic toxicities of prior therapy ≤Grade 2 (eg, peripheral neuropathy, residual alopecia) are allowed;
• Female participants who are pre-menopausal or have experienced menopause for less than 2 years and who have not undergone a hysterectomy, bilateral oophorectomy, or tubal occlusion must have a negative serum pregnancy test during screening and a serum or urine pregnancy test must be re-confirmed as negative no more than 72 hours before starting AG-270. Females of reproductive potential as well as fertile men with partners who are female of reproductive potential must agree to abstain from sexual intercourse or to use 2 effective forms of contraception (including at least 1 barrier form) from the time of giving informed consent, during the study, and for 6 months (for females) and for 3 months (for males) following the last dose of AG-270. Effective forms of contraception are defined as hormonal oral contraceptives, injectables, patches, intrauterine devices, double-barrier methods (eg, synthetic condoms, diaphragm, or cervical cap with spermicidal foam, cream, or gel), or male partner sterilization;
• Able to understand and has provided written informed consent. A legally authorized representative may consent on behalf of a participant who is otherwise unable to provide informed consent, if acceptable to and approved by the site and/or site's Institutional Review Board (IRB)/Independent Ethics Committee (IEC).
• AG-270 in Combination with Docetaxel
• a. Be ≥18 years of age;
• a. Have histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that has been treated with no more than 2 prior lines of cytotoxic chemotherapy in the setting of metastatic (Stage 4) disease. Three prior lines of cytotoxic chemotherapy for metastatic disease are allowed if one of the 3 lines was a maintenance treatment. Participants with solid tumors other than NSCLC for which docetaxel is indicated are eligible for the dose-escalation arm, but they also must have received no more than 2 prior lines of cytotoxic chemotherapy in the setting of metastatic disease; For both participants with NSCLC and participants with other malignancies prior treatment with taxanes is permitted, but prior treatment with docetaxel is not allowed. There is no limitation on the number of non-cytotoxic therapies that a participant with NSCLC or with another malignancy may have received;
• a. Have evidence of homozygous loss of CDKN2A and/or MTAP in the participant's tumor tissue. In the dose expansion phase of the combination, participants must have homozygous MTAP deletion;
• a. Have disease that can be clinically evaluated for improvement or progression. In the dose-expansion phase of this study arm, participants must have disease that is measurable, as defined by the RECIST Version 1.1 criteria for solid tumors (Eisenhauer et al, 2009);
• a. Have an ECOG PS of ≤1;
• a. Have a hemoglobin ≥9.0 g/dL without red blood cell transfusion for ≥1 month;
• a. Have an ANC ≥1.5 × 10\^9/L;
• a. Have a platelet count ≥100 × 10\^9/L;
• a. Have a serum total bilirubin ≤1.5 × ULN;

Where it is running

• Yale University — New Haven, Connecticut, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Beth Israel — Boston, Massachusetts, United States
• Dana Farber Cancer Institute — Boston, Massachusetts, United States
• Memorial Sloan Kettering Cance Center — New York, New York, United States
• Sarah Cannon Cancer Center — Nashville, Tennessee, United States
• Institut Gustave Roussy — Villejuif, France
• Hospital Universitario Vall d'Hebron — Barcelona, Spain

Full record on ClinicalTrials.gov

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