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

All Drugs and Chemicals

Antineoplastic Agents

Hormones

Immunomodulating Agents

Taxane

Part 1 will evaluate AMG 509 in participants with metastatic castration-resistant prostate cancer (mCRPC) who have been previously treated with novel hormonal therapy (NHT) and 1 to 2 prior taxanes.

The dose exploration phase of the study will estimate the MTD of AMG 509 using a Bayesian logistic regression model (BLRM; Neuenschwander et al, 2008).

RP2D may be identified based on emerging safety, efficacy, pharmacokinetics (PK), and pharmacodynamics (PD) data, as well as patient experience prior to reaching an MTD. Alternative dosing schedule(s) (including a third step dose) may be explored based on emerging efficacy, safety, PK data and patient experience.

During the dose expansion phase, individual cohorts of participants from China will be enrolled with a safety lead-in at 1 dose level below the MTD or RP2D followed by evaluation at the MTD or RP2D to confirm the safety, tolerability, MTD and/or RP2D of AMG 509 in Chinese participants.

Part 2 will explore the safety, tolerability, and PK of AMG 509 SC dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes.

Recommended phase 2 dose for SC monotherapy may be identified based on emerging safety, efficacy, PK, and PD data, as well as patient experience prior to reaching an MTD.

Part 3 will explore AMG 509 in participants with mCRPC who have received 1 prior NHT (may have been given for HSPC) and no prior taxanes (may have been given for HSPC). This dose expansion will be conducted to confirm safety, PK, and PD of AMG 509 at the MTD or RP2D determined in Part 1 dose exploration, and to obtain further safety and efficacy data and correlative biomarker analysis.

Part 4 will explore the safety, tolerability, and PK of AMG 509 for participants with mCRPC who have received no or 1/2 prior NHT (for hormone sensitive or castration-resistant disease) at dose regimens previously determined to be safe and tolerable in Part 1, in combination with abiraterone (Part 4A), or enzalutamide (Part 4B) and no or 1 prior taxane for hormone sensitive disease in Parts 4A and 4B. Part 4 consists of a dose exploration phase and a dose expansion phase.

This dose exploration study will estimate the MTD and/or RP2D of AMG 509 in combination with abiraterone or enzalutamide using a modified toxicity probability interval design. The dose-expansion phase will confirm safety, PK, and PD at the MTD or RP2D and to obtain further safety and efficacy data and correlative biomarker analysis.

Part 5 will evaluate the safety and tolerability of AMG 509 IV dosing in participants with mCRPC who have been previously treated with NHT and 1 to 2 prior taxanes, when administered in outpatient infusion centers.

The Part 5 dosing regimen and schedule was selected based on emerging data and DLRT recommendations and will utilize the doses explored in Part 1 dose-expansion phase

AMG 509 administered as an IV infusion (Parts 1, 3, 4 and 5) or SC injection (Part 2).

AMG 509

Abiraterone administered as oral tablets.

Abiraterone

Enzalutamide administered as oral tablets.

Enzalutamide

Amgen Call Center

Evaluate the safety and tolerability of AMG 509 in adult participants and determine the maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D).

Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer

A Phase 1 Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 509 in Subjects With Metastatic Castration-Resistant Prostate Cancer

De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

To characterize the pharmacokinetics (PK) of AMG 509

To evaluate preliminary anti-tumor activity of AMG 509

To evaluate preliminary anti-tumor activity of AMG 509. Measure of disease burden based on PCWG3-recommended endpoints.

Amgen

Anna Spreafico, MD

Aileen Trang

This is a single-center, investigator-initiated, non-interventional study evaluating the role of the intestinal microbiome and autoimmune panels as a predictor for developing ≥ Grade 2 CTCAE v5.0 immune-related adverse event (irAE) and/or requiring systemic immunosuppression for irAEs in advanced solid tumor patients receiving immunooncology (IO) combinations at the Princess Margaret Cancer Centre. This is a minimal risk study involving the analysis of patient samples and does not involve therapeutic intervention.

The study will involve a prospective cohort of up to 120 patients and it is anticipated that patient accrual will be completed within 18 months.

Patients will receive IO combination as per their specific protocols from their other clinical trial or per their standard of care and samples will be collected at multiple time-points. No additional visits to the hospital will be needed for this study as safety assessments are already captured for all patients based on their participation in a clinical trial or per their standard of care.

Accumulating evidence supports that differential composition of fecal microbiome influences response to immunotherapy and development of colitis. Microbiome with different profiles are also associated with multiple diseases, including gastrointestinal (GI) or non-GI auto-immune pathologies. Little is known about the relationship between the microbiome composition or fecal calprotectin (fCal) and the development of non-colitis immune-related adverse events (irAEs) during treatment with IO combinations.

Autoimmune conditions and irAEs from immune checkpoint inhibitors (ICI) drugs both involve loss of tolerance to endogenous antigens and produce similar clinical presentations. ICI can increase humoral response. However, to date there is no evidence that autoimmune panels are correlated with the development of irAEs during IO combination therapy.

These findings suggest that analyzing the microbiome and autoimmune panels of patients treated with IO combinations at multiple time-points may be feasible. In addition, baseline, early shift and changes in microbiome and autoimmune panels at time of a serious irAE may be correlated with the development of serious irAEs and may change with appropriate immunosuppressive regimens.

We hypothesize that analysing the microbiome and autoimmune panels of patients treated with immunooncology (IO) combinations at multiple time-points is feasible. Additionally, we hypothesize that baseline, early shift and changes in microbiome and autoimmune panels at time of a serious immune-related adverse event (irAE) is correlated with the development of serious irAEs and will change with appropriate immunosuppressive regimens.

Stool and blood samples at multiple time-points in patients undergoing treatment with immunooncology (IO) combination therapy.

Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients

Microbiome composition through 16S rRNA sequencing with PFS by RECIST v1.1 and iRECIST.

Microbiome composition through 16S rRNA sequencing with ORR by RECIST v1.1 and iRECIST.

Correlate the reactivity of baseline auto-antibodies detected through the 162 IgM and IgG antigen microarray with ORR per RECIST v1.1 and iRECIST.

Correlate the reactivity of baseline auto-antibodies detected through the 162 IgM and IgG antigen microarray with PFS per RECIST v1.1 and iRECIST.

Change in microbiome composition as outlined above with ORR per RECIST v1.1 and iRECIST.

Change in microbiome composition as outlined above with PFS per RECIST v1.1 and iRECIST.

Change in reactivity of auto-immune antibodies as outlined above with ORR per RECIST v1.1 and iRECIST.

Change in reactivity of auto-immune antibodies as outlined above with PFS per RECIST v1.1 and iRECIST.

Correlation of bacteria taxa composition through 16S rRNA sequencing with radiomic analysis.

Correlation of auto-immune antibodies as outlined above with radiomic analysis

To assess the feasibility, the endpoint will be deemed feasible if \>50% of patients have biospecimens collected in at least 2 time-points.

Correlation between bacteria taxa obtained through 16S rRNA sequencing and irAEs.

Correlation between auto-antibodies detected through the 162 IgM and IgG antigen microarray with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.

Correlation between fCal detection at baseline to development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.

Correlate changes in bacteria taxa composition through 16S rRNA sequencing from baseline samples to early time-point, with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs

Correlate the changes of auto-immune antibodies reactivity obtained through the 162 IgM and IgG antigen microarray from baseline to early time-point with the development of ≥ Grade 2 CTCAE v5.0 irAEs and/or requiring systemic immunosuppression for irAEs.

Correlate the changes in fCal positivity from baseline to early time-point with the development of ≥ Grade 2 CTCAE v5.0 colitis and/or requiring systemic immunosuppression for colitis.

Monitor changes in bacteria taxa through 16S rRNA sequencing; reactivity of autoimmune antibodies through 162 IgM and IgG antigen microarray; and positivity of fCal at baseline, early time-point, at the time of event diagnosis, and at the time of event resolution

University Health Network, Toronto

Symptoms and General Pathology

Recurrence

Carcinoma

Carcinoma, Squamous Cell

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Nivolumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

IK-175 + nivolumab

Katherine Kim, MD

Karim Malek, MD

This is a phase 1b study in adult patients diagnosed with resistant or recurrent head and neck squamous cell carcinoma (HNSCC) designed to assess the safety and tolerability of IK-175 in combination with nivolumab. Disease response, pharmacokinetics (PK), pharmacodynamics, and response biomarkers will also be assessed.

This is an open-label, multicenter, phase 1b dose-expansion study to evaluate the safety, tolerability, preliminary antitumor activity, PK, and pharmacodynamics of 2 dose levels of IK-175, administered PO in combination with nivolumab, in patients with primary PD-1-resistant metastatic or locally incurable, recurrent HNSCC for which standard therapy is no longer effective or is intolerable.

Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer

A Phase 1b, Open-Label, Single-Arm Dose-Expansion Study of IK-175, an Oral Aryl Hydrocarbon Receptor Inhibitor, in Combination With Nivolumab in Patients With Primary PD-1 Inhibitor Resistant Metastatic or Locally Incurable, Recurrent HNSCC

Number and severity of TEAEs as assessed by CTCAE 5.0

Number and severity of TRAEs as assessed by CTCAE 5.0

Number and severity of SAEs as assessed by CTCAE 5.0

Number and severity of adverse events leading to dose modifications and/or treatment discontinuation as assessed by CTCAE 5.0

ORR is defined as the percentage of participants with confirmed complete response (cCR) or confirmed partial response (cPR) per RECIST 1.1

DCR is defined as the percentage of participants with no occurrence of progressive disease with either cCR, cPR, or stable disease \[SD\] ≥ 16 weeks per RECIST 1.1 from the beginning of study therapy

DOR is defined as the time from the first documented CR or PR per RECIST 1.1 until disease progression or death from any cause

PFS is defined as the length of time from the beginning of study treatment to the first observed disease progression or death due to any cause

OS is defined as the length of time from the beginning of study treatment to the date of death due to any cause

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of AMG 509 in Participants With Metastatic Castration-Resistant Prostate Cancer	NCT04221542	Prostate Cancer	AMG 509 Abiraterone Enzalutamide	18 Years -	Amgen
Prospective Analysis of Intestinal Microbiome and Autoimmune Panels as Predictors of Toxicity in ImmunOncology Patients	NCT04107311	Solid Tumor		18 Years -	University Health Network, Toronto
Oral AHR Antagonist in Combination With Nivolumab in Patients With PD-1 Resistant Metastatic or Recurrent Head and Neck Cancer	NCT05472506	Head and Neck S... Head and Neck C... Head Cancer Neck Cancer Head Cancer Nec... Neck Carcinoma	IK-175 + nivolu...	18 Years -	Ikena Oncology

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