Intraperitoneal MCY-M11 (Mesothelin-targeting CAR) for Treatment of Advanced Ovarian Cancer and Peritoneal Mesothelioma

Study Overview
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Brief Summary
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This is a phase 1 dose escalation study to characterize the feasibility, safety and tolerability of MCY-M11 when administered as an intraperitoneal (IP) infusion for 3 weekly doses for women with platinum resistant high grade serous adenocarcinoma of the ovary, primary peritoneum, or fallopian tube, and subjects with peritoneal mesothelioma with recurrence after prior chemotherapy. The study will also assess multiple cycles of treatment and adding preconditioning with cyclophosphamide.

Official Title
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A Phase 1 Study of Intraperitoneal MCY-M11 Therapy for Women With Platinum Resistant High Grade Serous Adenocarcinoma of the Ovary, Primary Peritoneum, or Fallopian Tube, or Subjects With Peritoneal Mesothelioma With Recurrence After Prior Chemotherapy

Conditions
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Peritoneal Mesothelioma, Fallopian Tube Adenocarcinoma, Adenocarcinoma of the Ovary, Primary Peritoneal Carcinoma

Intervention / Treatment
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* Biological: MCY-M11
* Drug: Cyclophosphamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be able to undergo peripheral blood leukapheresis; have successful placement of an intraperitoneal catheter Be diagnosed with one of the following: metastatic or unresectable high grade serous adenocarcinoma involving the ovary, primary peritoneum, or fallopian tube with peritoneal involvement, not including mixed histologies, OR unresectable epithelioid or biphasic peritoneal mesothelioma Be at least 4 weeks from previous anti-cancer therapy Have a life expectancy of greater than 3 months. Exclusion Criteria: Females who are pregnant, trying to become pregnant, or breastfeeding Diagnosis of HIV or chronic active Hepatitis B or C Symptomatic or uncontrolled brain metastases requiring current treatment Impaired cardiac function or clinically significant cardiac disease Lack of recovery of prior mild adverse events due to earlier therapies Active infection Another previous or current malignancy within the last 3 years, with exceptions Concomitant chronic use of steroids or NSAIDs Concomitant use of complementary or alternative medication or therapy Autoimmune disease or inflammatory disease within previous 5 years

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1<br>3-6 subjects will receive a starting dose of MCY-M11 via intraperitoneal infusion once weekly for 3 weeks | Biological: MCY-M11<br>* Intraperitoneal administration<br>Drug: Cyclophosphamide<br>* Intravenous administration for preconditioning<br>|
| Experimental: Cohort 2 and 2i<br>3-6 subjects will receive a higher dose of MCY-M11 via intraperitoneal infusion once weekly for 3 weeks (cohort 2); 3-6 subjects will receive MCY-M11 and cyclophosphamide preconditioning (cohort 2i) | Biological: MCY-M11<br>* Intraperitoneal administration<br>Drug: Cyclophosphamide<br>* Intravenous administration for preconditioning<br>|
| Experimental: Cohort 3 and 3i<br>3-6 subjects will receive a higher dose of MCY-M11 via intraperitoneal infusion once weekly for 3 weeks (cohort 3); 3-6 subjects will receive MCY-M11 and cyclophosphamide preconditioning (cohort 3i) | Biological: MCY-M11<br>* Intraperitoneal administration<br>Drug: Cyclophosphamide<br>* Intravenous administration for preconditioning<br>|
| Experimental: Cohort 4 and 4i<br>3-6 subjects will receive a higher dose of MCY-M11 via intraperitoneal infusion once weekly for 3 weeks (cohort 4); 3-6 subjects will receive MCY-M11 and cyclophosphamide preconditioning (cohort 4i) | Biological: MCY-M11<br>* Intraperitoneal administration<br>Drug: Cyclophosphamide<br>* Intravenous administration for preconditioning<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of adverse events as assessed by CTCAE v.5.0 | number and severity of adverse events according to NCI CTCAE v.5.0 | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Evaluation Criteria in Solid Tumors (RECIST) | tumor response scored by RECIST criteria | from first MCY-M11 dosing to first documented progression, assessed up to 24 months | 
| Immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) | tumor response scored by irRECIST criteria | from first MCY-M11 dosing to first documented progression, assessed up tp 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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platinum resistant, high grade serous adenocarcinoma, recurrence after chemotherapy, intraperitoneal