Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Antineoplastic Agents

All Drugs and Chemicals

Analgesics

Pembrolizumab

Interleukin-2

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

LAVA-1207 with Low-Dose Subcutaneous IL-2 (LDSC IL-2)

In part 1 \& part 2

• LAVA-1207 will be administered via intravenous infusion.

LAVA-1207

Pembrolizumab will be administered via intravenous infusion

LAVA-1207 plus Pembrolizumab

Clinical Trials Administrator

Joel Picus, MD

Kelsey Egberts

David R. Wise, MD, PhD

Hannan Aslam

Umang Swami, MD, MS

Susan Sharry

Clinical Trials Management

This is a phase 1/2a, first-in-human study to evaluate Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207 alone or with low dose interleukin-2 or Pembrolizumab, in patients with therapy refractory metastatic castration resistant prostate cancer.

This trial is an open-label Phase 1 and 2a dose escalation trial with an expansion cohort to investigate the safety and tolerability of LAVA-1207 alone or with low dose interleukin-2 or Pembrolizumab, in patients with therapy refractory mCRPC.

Trial of LAVA-1207 in Patients With Therapy Refractory Metastatic Castration Resistant Prostate Cancer (mCRPC) Resistant Prostate Cancer

A Phase 1/2a Open-label Trial to Evaluate the Safety, Tolerability, PK, PD, Immunogenicity, and Antitumor Activity of LAVA-1207, a PSMA-targeting Bispecific γδ-T Cell Engager, Alone or With Low Dose Interleukin-2 or Pembrolizumab, in Patients With Therapy Refractory mCRPC

To evaluate the effect of study treatment on circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA)

Frequency and severity of Adverse Events using the Common Terminology Criteria and grading for Adverse Events and grading for CRS

DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 28 days of treatment.illness, or concomitant medications and is occurring during the first 28 days of treatment.

According to immune Response Evaluation Criteria in Solid Tumors (RECIST and iRECIST) in patients with measurable disease.

Area under the plasma concentration versus time curve (AUC) of LAVA-1207 will be assessed in all patients

Development of antibodies (anti-drug antibodies) to LAVA-1207 will be evaluated

Binding of LAVA-1207 to Vγ9Vδ2-T cells will be measured in whole blood

Merck Sharp & Dohme LLC

Lava Therapeutics

Skin and Connective Tissue Diseases

Immune System Diseases

Breast Neoplasms

Hypersensitivity

Breast Diseases

Skin Diseases

Hormones

Estrogens

Mitogens

Palbociclib

Protein Kinase Inhibitors

Enzyme Inhibitors

Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 as well as expansion cohorts and a Phase 2 cohort.

Dose escalation cohorts are planned to determine maximum tolerated dose(MTD) or recommended phase 2 dose (RP2D) of ZN-c5 in combination with palbociclib as well as a Phase 2 cohort.

ZN-c5

Palbociclib (IBRANCE®) is an approved drug

Zeno Alpha, Inc.

This is a Phase 1/2, open-label, multicenter, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics, and preliminary efficacy of ZN-c5 administered orally in subjects with advanced estrogen receptor positive, human epidermal growth factor receptor 2 negative (ER+/HER2-) breast cancer. ZN-c5 will be evaluated both as monotherapy and in combination with palbociclib (IBRANCE®).

Dose escalation cohorts are planned in monotherapy and combination as well as monotherapy dose expansion, and monotherapy and combination Phase 2.

A Study of ZN-c5 in Subjects With Breast Cancer

A Phase 1/2 Open Label, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Anti-Tumor Activity of ZN-c5 Alone and in Combination With Palbociclib in Subjects With Estrogen-Receptor Positive, Human Epidermal Growth Factor Receptor-2 Negative Advanced Breast Cancer

Measured by the number of treatment-emergent adverse events

Zeno Alpha Inc.

Blood and Lymph Conditions

Rare Diseases

Lymphoma

Hematologic Neoplasms

Hematologic Diseases

Lymphosarcoma

Immunomodulating Agents

Adjuvants, Immunologic

This portion of the study will evaluate the safety and pharmacology of a range of Tomivosertib (eFT-508) doses administered daily in subjects with previously treated lymphomas

This portion of the study provides cohort expansion to further explore the safety, pharmacology, and clinical activity of a single dose level of Tomivosertib (eFT-508) monotherapy in subjects with specific previously treated lymphomas

Tomivosertib (eFT-508)

Jeremy Barton, MD

This clinical trial is a Phase 1-2, open-label, sequential-group, dose-escalation and cohort-expansion study evaluating the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of Tomivosertib (eFT-508). The study will evaluate oral daily administration of Tomivosertib (eFT-508). Treatment and study subject evaluation will be performed in 21-day cycles.

A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Oral Tomivosertib (eFT-508) in Subjects With Hematological Malignancies

Effector Therapeutics

Symptoms and General Pathology

Recurrence

Glioblastoma

Astrocytoma

Glioma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Temozolomide

Macitentan

Antineoplastic Agents, Alkylating

Alkylating Agents

Endothelin A Receptor Antagonists

Endothelin Receptor Antagonists

Macitentan in combination with dose-dense temozolomide

Macitentan 30, 60, 90 mg or higher in 30 mg dose increments, given orally, up to 150 mg, then 225 mg, 300 mg and 375 mg, unless otherwise decided by the Safety Monitoring Committee. Dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off.

Phase 1 Dose Escalation

Macitentan given orally and daily at doses/schedule determined from the dose escalation period. Dose-dense temozolomide 150mg/m2 body surface area alternating 1 week on 1 week off.

Phase 1b

Macitentan dosed initially for 8-14 days prior to craniotomy, then treatment interrupted from time of craniotomy until 7 days before start of dose dense temozolomide therapy. dose-dense temozolomide 150 mg/m2 body surface area alternating 1 week on 1 week off.

Ancillary Study

This is an open-label, single arm, Phase 1 study to assess the safety and tolerability of macitentan in combination with dose-dense temozolomide in adult patients with recurrent glioblastoma or gliosarcoma. The study is composed of three parts. A Phase 1 Dose Escalation Period with a traditional 3+3 design will determine the maximum tolerated dose of macitentan in combination with dose-dense temozolomide. A Phase 1b Period will expand the safety and tolerability data of two doses of macitentan and dose-dense temozolomide selected from the Dose Escalation Period and explore efficacy. An Ancillary Study will further evaluate the effects of macitentan on biomarkers in brain tumor tissue.

The study is planned to have a minimum duration of 12 months. The study will end when all patients (excluding those prematurely withdrawn or lost to follow-up) in each part of the study have completed a visit at month 12 and 30 days of safety follow-up.

Clinical Study on the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide in Patients With Recurrent Glioblastoma

A Phase 1/1b, Open-label Study in Patients With Recurrent Glioblastoma to Assess the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide

for all study periods: systolic and diastolic blood pressure \[supine and standing\], average of the two measurements and pulse rate.

Actelion

Heart and Blood Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Leukemia, Lymphoid

Multiple Myeloma

Neoplasms, Plasma Cell

Leukemia, Lymphocytic, Chronic, B-Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hemorrhagic Disorders

Lymphoproliferative Disorders

Immunoproliferative Disorders

Lymphatic Diseases

Leukemia, B-Cell

Chronic Disease

Disease Attributes

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Chronic Graft Versus Host Disease

Chronic Lymphocytic Leukemia

Acute Graft Versus Host Disease

Analgesics, Non-Narcotic

Part 1 (dose escalation): LAVA-051 will be given to patients via intravenous (IV) infusion with dose escalation. A selected group of patients will also receive a low dose of interleukin 2 via subcutaneous injection.

* Group A: LAVA-051
* Group B: LAVA-051 + low dose interleukin 2

Part 2 (dose expansion): patients will receive LAVA-051 at the dose and regimen established in Part 1 of the study

In part 1 and part 2, LAVA-051 will be administered via intravenous (IV) infusion

LAVA-051

In Part 1 and Part 2, a low dose of interleukin 2 will be given via subcutaneous injection with LAVA-051 in a selected group of patients

Interleukin 2

A phase 1/2a, first-in-human trial to evaluate the safety and tolerability of LAVA-051 in patients with relapsed or refractory Chronic Lymphocytic Leukemia (CLL), Multiple Myeloma (MM), or Acute Myeloid Leukemia (AML).

An open-label, phase 1/2a dose escalation trial with disease-specific expansion cohorts to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary anti-tumor activity of LAVA-051 in patients with relapsed or refractory CLL, MM, or AML.

Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML

A Phase 1/2a Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of LAVA-051 in Patients With Relapsed or Refractory CLL, MM, or AML

Frequency, severity, and grading of Adverse Events using the Common Terminology Criteria and grading for Adverse Events (CTCAE) v5.0. CRS will be evaluated using the ASTCT.

A DLT is defined as an adverse event that is unrelated to disease progression, intercurrent illness, or concomitant medications and is occurring during the first 28 days of treatment. These events will be classified according to the CTCAE v5.0; CRS will be evaluated according to the ASTCT consensus criteria

Antitumor response for CLL per iwCLL guidelines, MM per IMWG-based response criteria, and AML per ELN criteria

Area under the plasma concentration versus time curve (AUC) of LAVA-051 will be assessed in all patients treated with LAVA-051

Development of antibodies (anti-drug antibodies) to LAVA-051 will be evaluated

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Trial of LAVA-1207 in Patients With Therapy Refractory Metastatic Castration Resistant Prostate Cancer (mCRPC) Resistant Prostate Cancer	NCT05369000	Metastatic Cast...	LAVA-1207 LAVA-1207 plus ...	18 Years -	Lava Therapeutics
A Study of ZN-c5 in Subjects With Breast Cancer	NCT03560531	Breast Cancer	ZN-c5 Palbociclib	18 Years -	Zeno Alpha Inc.
A Phase 1-2 Dose-Escalation and Cohort-Expansion Study of Oral Tomivosertib (eFT-508) in Subjects With Hematological Malignancies	NCT02937675	Lymphoma	Tomivosertib (e...	18 Years -	Effector Therapeutics
Clinical Study on the Safety and Tolerability of Macitentan in Combination With Dose-dense Temozolomide in Patients With Recurrent Glioblastoma	NCT01499251	Glioblastoma	Phase 1 Dose Es... Phase 1b Ancillary Study	18 Years -	Actelion
Trial of LAVA-051 in Patients With Relapsed/Refractory CLL, MM, or AML	NCT04887259	Chronic Lymphoc... Multiple Myelom... Acute Myeloid L...	LAVA-051 Interleukin 2	18 Years -	Lava Therapeutics

Spots Global Cancer Trial Database for phase 1 dose escalation