Le Kremlin Bucetre, France

A First-in-human (FIH), Phase I Study of PTX-912 in Patients with Locally Advanced/Metastatic Solid Tumors

A Study of GLB-001 in Patients With Relapsed or Refractory Acute Myeloid Leukemia or Relapsed or Refractory Higher Risk Myelodysplastic Syndromes

A standard 3+3 dose-escalation design will be applied to evaluate a set of several dose levels to determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of GLB-001 in R/R AML or R/R HR-MDS patients who are eligible for DLT evaluation. The actual dose-escalation magnitude or dosing frequency may be adjusted based on the available PK and safety data in human. After the MTD or MAD of GLB-001 is defined in Phase 1a, 1 or 2 dose levels will be selected for expansion per safety review committee (SRC) recommendation, approximately 12 patients will be enrolled per dose level. Recommended phase 2 dose (RP2D) will be selected based on the results of PK, PD, safety and efficacy in the dose escalation and expansion study.

A Study to Evaluate the Safety and Efficacy of A2B694, a Logic-gated CAR T, in Participants with Solid Tumors That Express MSLN and Have Lost HLA-A*02 Expression

This is a seamless phase 1/2, multi-center, open-label study that enrolls adults with recurrent unresectable, locally advanced, or metastatic (considered non-curative) CRC, NSCLC, PANC, OVCA, MESO or other solid tumors with MSLN expression. Subjects must be germline HLA-A*02 heterozygous, with tumors that express MSLN and have lost HLA-A*02 expression. The purpose of Phase 1 of this study is to determine the safety and the optimal dose of A2B694 (after PCLD) in participants with solid tumor disease. The purpose of Phase 2 of this study is to determine the further safety and efficacy (how well it treats the solid tumor disease) of A2B694. The treatment available for these cancers and other solid tumors can be toxic, debilitating, and fatal. In the recurrent unresectable, locally advanced, or metastatic setting, the intent of standard of care treatment is typically palliative rather than curative, and has not changed significantly in several decades. A2 Bio hypothesizes that A2B694 Tmod CAR T-cell therapy will enable the killing of tumor target cells (those cells that express MSLN and have LOH for HLA-A*02 protein). Additionally, normal healthy cells that maintain HLA-A*02 expression and co-express MSLN (eg, lung tissue) will not be targeted due to the blocker portion of the Tmod CAR T cell that acts as a self-regulated safety switch that protects normal tissue from damage. A2 Bio believes this will provide a therapeutic safety window compared to previous solid tumor targeting therapies. This hypothesis will be explored in the study. Participants for this study must enroll and have their T cells collected (apheresis) in the pre-screening BASECAMP-1 study (NCT04981119). T cells are collected, processed and stored for each participant. Upon disease progression the participant may screen for this study (EVEREST-2) and the participant's T cells are manufactured and then infused following PCLD regimen. There is no time requirement between the studies, and patients may go directly from BASECAMP-1 to EVEREST-2 based on their own disease course.

Mezigdomide (CC-92480) Post Idecabtagene Vicleucel in Treating Patients With Relapsed Multiple Myeloma

PRIMARY OBJECTIVE: I. To evaluate the safety and tolerability of mezigdomide (CC-92480) given post idecabtagene vicleucel when administered as a continued therapy. SECONDARY OBJECTIVES: I. To evaluate the anti-tumor activity of mezigdomide (CC-92480) when administered post idecabtagene vicleucel. II. To determine the persistence of CAR T cells at day 90 (D90), day 180 (D180), and day 365 (D365) after start of mezigdomide (CC-92480) therapy. EXPLORATORY OBJECTIVES: I. To assess levels of serum BCMA monthly at day 1 of every cycle. II. To assess the effects of mezigdomide (CC-92480) on non-cancer immune cells in the peripheral blood and bone marrow samples. OUTLINE: This is a dose-escalation study of mezigdomide. Starting between 30 and 90 days after infusion of idecabtagene vicleucel, patients receive mezigdomide orally (PO) on days 1-21 or days 1-14 of each cycle. Treatment repeats every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo positron emission tomography (PET)/computed tomography (CT) during screening. Patients also undergo bone marrow aspiration and blood sample collection throughout the study. After completion of study treatment, patients are followed up at 30 days, every 3 months within 1 year of start of treatment, and then every 6 months until progression or for up to 2 years.

Nivolumab and Ipilimumab With and Without Camu Camu for the Treatment of Patients With Metastatic Renal Cell Carcinoma

PRIMARY OBJECTIVE: I. To determine the effect of camu camu in combination with nivolumab/ipilimumab on Ruminococcus abundance in stool samples of patients with metastatic renal cell carcinoma (mRCC). SECONDARY OBJECTIVES: I. To evaluate the effect of camu camu on the clinical efficacy of the nivolumab/ipilimumab combination. II. To determine the effect of camu camu on systemic immunodulation of the nivolumab/ipilimumab combination in patients with mRCC. III. To describe the toxicity and safety profile of the use of camu camu in combination with nivolumab/ipilimumab. IV. To determine the effect of camu camu on gut microbiome diversity and function. OUTLINE: Patients are randomized to 1 of 2 arms. ARM 1: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and ipilimumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1 of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo computed tomography (CT) and/or bone scan and/or magnetic resonance imaging (MRI) on trial. ARM 2: Patients receive nivolumab IV over 30 minutes on day, ipilimumab IV over 30 minutes on day 1, and camu camu orally (PO) once a day (QD) continuously with each cycle. Cycles repeat every 3 weeks for cycles 1-4. Beginning cycle 5, patients receive nivolumab over 30 minutes on day 1, and camu camu PO QD of each cycle. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo blood and stool sample collection and undergo CT and/or bone scan and/or MRI on trial. After completion of study treatment, patients are followed up every 12 weeks until time of death or formal withdrawal from the study, whichever comes first.

CMV-MVA Triplex Vaccination in HLA-Matched Related Stem Cell Donors for the Prevention of CMV Infection in Patients Undergoing Hematopoietic Stem Cell Transplant

PRIMARY OBJECTIVE: I. To determine whether multi-peptide CMV-modified vaccinia Ankara vaccine (Triplex) is safe and effective in protecting against CMV events defined as viremia requiring antiviral preemptive therapy (PET) or CMV end organ disease. SECONDARY OBJECTIVE: I. To examine if Triplex vaccination of hematopoietic stem cell transplant (HCT) donors has an impact on CMV events. OUTLINE: Donors are randomized to 1 of 2 arms. ARM I: DONORS: Donors receive Triplex vaccine intramuscularly (IM) on day 0 and then undergo stem cell mobilization with granulocyte colony-stimulating factor (G-CSF) on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study. ARM II: DONORS: Donors receive placebo IM on day 0 and undergo stem cell mobilization with G-CSF on days 5 to 9 and apheresis for peripheral blood stem cell collection on days 10 to 14 per standard of care. Donors may optionally undergo blood sample collection on study. RECIPIENTS: Recipients undergo pre-transplant conditioning on days -60 to 0 and undergo HCT with the donor peripheral blood stem cells within 9 weeks of donor vaccination on day 0. Recipients undergo blood sample collection on study. After completion of study treatment, donors follow up on days 90, 180 and 365 after vaccination and recipients follow up on days 14, 28, 42, 56, 70, 100, 140, 180, 270, and 365 after transplantation.

A Study of onCARlytics (CF33-CD19) in Combination With Blinatumomab in Adults With Advanced or Metastatic Solid Tumors (OASIS)

CF33-CD19, a novel chimeric orthopoxvirus, will be administered as a monotherapy or in combination with blinatumomab and with or without hydroxyurea to assess the safety and efficacy of the treatment regimens as well as immunological changes in the tumour microenvironment. Subjects eligible for treatment include those with any metastatic or advanced solid tumor who have documented radiological progression per RECIST following at least two prior lines of therapy. All enrolled monotherapy subjects will be treated with CF33-CD19 on Day 1 and 8 of Cycle 1 and then on Day 1 of each 21-day cycle thereafter. Subjects treated with the combination regimen will receive CF33-CD19 on Days 1 and 15 of each 28-day cycle. In addition, they will receive blinatumomab as a 7-day continuous infusion from Days 2-9 and Days 16-23 of each cycle.

Acalabrutinib, Obinutuzumab, and Glofitamab for the Treatment of Relapsed or Refractory Mantle Cell Lymphoma

PRIMARY OBJECTIVES: I. Evaluate the safety and tolerability of a regimen combining acalabrutinib and glofitamab in patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). (Safety Lead-In) II. Estimate the complete response (CR) rate in R/R MCL patients treated with acalabrutinib plus glofitamab. (Phase 2) SECONDARY OBJECTIVES: I. Estimate the minimal residual disease (MRD) negativity rate, time to response, duration of response (DOR), progression-free survival (PFS), overall survival (OS), and patient-reported quality of life measures (HRQOL) in R/R MCL patients treated with acalabrutinib plus glofitamab. II. Evaluate the toxicity of acalabrutinib plus glofitamab for R/R MCL. EXPLORATORY OBJECTIVES: I. Examine the prognostic value of MRD assessment by next-generation sequencing (NGS) and circulating cell-free tumor deoxyribonucleic acid (DNA) (ctDNA) assessment in patients with R/R MCL treated with acalabrutinib combined with glofitamab. II. Examine the immune reconstitution, T-cell fitness, and immunomodulatory effects in patients with R/R MCL treated with acalabrutinib combined with glofitamab. III. Examine the evolution of tumor genetic profile and microenvironment in patients with R/R MCL treated with acalabrutinib combined with glofitamab. OUTLINE: Patients receive acalabrutinib orally (PO) twice daily (BID) of each cycle, obinutuzumab intravenously (IV) on days 1 and 7 of cycle 1 only, and glofitamab IV over 2-4 hours on days 8 and 15 of cycle 1 and day 1 of subsequent cycles. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD positive complete response (CR), partial response (PR), or stable disease (SD) after 12 cycles of protocol therapy may continue receiving single agent acalabrutinib per standard of care during the follow-up phase of the study. Patients also undergo a echocardiography (ECHO) or multigated acquisition scan (MUGA) during screening, as well as positron emission tomography (PET)/computed tomography (CT) or CT, and blood specimen collection throughout the trial. Patients may also undergo bone marrow biopsies throughout the trial. Upon completion of study treatment, patients are followed up at 30 days and then every 3 months for response and bi-annually for survival, for up to 4 years from start of treatment.

Geriatric Assessment Guided Interventions to Accelerate Functional Recovery After CAR-T Therapy for Patients 60 Years and Older With B-cell Non-Hodgkin Lymphoma or Multiple Myeloma, GOCART Study

PRIMARY OBJECTIVE: I. Evaluate the effects of a GA-informed multi-disciplinary intervention in attenuating physical function decline among older patients receiving CAR-T therapy at day +30 post-CAR-T infusion. SECONDARY OBJECTIVES: I. Determine success in coordinating trimodality optimization before lymphodepletion. II. Compare rates of geriatric syndromes of frailty, cognitive impairment and malnourishment in SOC and GA-intervention cohorts at 30 days post-CAR-T infusion. III. Evaluate rates and duration of CAR-T related neurotoxicity in SOC and GA-intervention groups. EXPLORATORY OBJECTIVES: I. Quantify trimodality optimization intensity throughout treatment course. II. Compare longitudinal trajectory of Short Physical Performance Battery (SPPB), frailty, cognitive impairment and malnourishment between the two arms, at day +100 post-CAR-T infusion. III. Evaluate quality of life trajectories using the Patient Reported Outcomes Measurement Information System (PROMIS) Global Health Scale at baseline and days +30 and +100 in both cohorts. IV. Incidence of intensive care unit (ICU) admissions by day 100. V. Overall survival, response rate and progression-free survival through one year. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients undergo GA before lymphodepleting chemotherapy and recommendations based on assessment results communicated to treating physicians. Patients receive physical therapy (PT) and delirium prevention education prior to lymphodepletion, at least once before CAR-T therapy, at least 2 times a week while inpatient, and at least once every other week outpatient up to day 30. Additionally, patients receive personalized nutritional guidance from a registered dietician prior to lymphodepletion, prior to CAR-T therapy and at least once a week up to day 30. ARM II: Patients undergo GA and receive standard of care throughout study. After completion of study treatment, patients are followed up at day 100 and then up to 1 year.

A Study of TRK-950 When Used in Combination with Ramucirumab and Paclitaxel in Patients with Gastric Cancer

This study will assess and compare the efficacy, safety, pharmacokinetics (PK), optimal dose and anti-drug antibodies (ADA) and neutralizing antibodies (NAbs) development of TRK-950 at two separate dose levels in combination with RAM + PTX as compared with RAM + PTX treatment alone in participants with gastric or gastro-esophageal junction (GEJ) adenocarcinoma. The primary objective is progression free survival (PFS). Secondary objectives are overall survival, objective response rate, best overall response, duration of response, disease control rate, safety, pharmacokinetics, and immunogenicity of TRK-950 when used in combination with RAM+PTX.