Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Neoplasm Metastasis

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

Dermatologic Agents

All Drugs and Chemicals

Photosensitizing Agents

DIOMED laser + photosensitizing agent injected intralesionally and topical immuno-modulating cream

Photoimmunotherapy

Murad Alam, MD

A novel treatment for metastatic melanoma combining a laser and an immune-system stimulating cream.

A novel treatment for metastatic melanoma combining a laser and an immune-system stimulating cream with or without injection of a substance that makes the tumor more sensitive to the laser.

A Novel Treatment for Metastatic Melanoma

In Situ Photoimmunotherapy: A Tumor Directed Treatment for Advanced Melanoma With Cutaneous Metastases

Northwestern University

Professor in Dermatology, Otolaryngology - Head and Neck Surgery, and Surgery-Organ Transplantation

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Squamous Cell Carcinoma of Head and Neck

Neoplasms, Glandular and Epithelial

Neoplasms, Squamous Cell

ASP-1929 640 mg/m\^2 treatment by intravenous (IV) infusion followed approximately 24 hours later by illumination (also termed as photoimmunotherapy \[PIT\]) of tumor(s) using the PIT690 Laser System with a 690 nm light dose of 50 J/cm\^2 for superficial illumination and 100 J/cm of diffuser length for interstitial illumination. During the illumination procedure, fluorescence of the IR700 component of ASP-1929 will be imaged with a Shimadzu Fluorescence Imaging System camera. Patients will undergo standard of care surgery with or without chemotherapy or radiation approximately 21 days after ASP-1929 PIT treatment.

ASP-1929 640 mg/m\^2 IV infusion followed approximately 24 hours later by photoimmunotherapy

ASP-1929 Photoimmunotherapy

Rakuten Medical Study Team

Vassiliki Saloura, MD, Ph.D

Vassiliki Saloura, MD

A Phase 2, Open-label, Single-arm, Window of opportunity Study of ASP-1929 Photoimmunotherapy with Fluorescence Imaging in Patients with Operable Primary or Recurrent Head and Neck or Cutaneous Squamous Cell Carcinoma

All patients will receive a combination of ASP-1929 and Photoimmunotherapy (PIT). During illumination procedure, fluorescence of the IR700 component of ASP-1929 will be imaged at a wavelength in the vicinity of 830 nm with a Shimadzu Fluorescence Imaging System camera. Patients will undergo standard of care surgery approximately 21 days after ASP-1929 PIT treatment.

ASP-1929 Photoimmunotherapy (PIT) Study in Patients With Recurrent Head/Neck Cancer

Phase 2, Open-label, Single-arm, Window of Opportunity Study of ASP-1929 Photoimmunotherapy With Fluorescence Imaging in Patients With Operable Primary or Recurrent Head and Neck or Cutaneous Squamous Cell Carcinoma

Proportion of patients with pathologic tumor response-2 (pTR-2) of ASP-1929 PIT-treated lesions. A patient is a pTR-2 responder if overall pTR of ASP-1929 PIT-treated tumors (including primary tumor and lymph node) is greater than or equal to 50% (pTR-2)

Local relapse rate (at ASP-1929 PIT-treated site) at one year after surgery

Time to local relapse at ASP-1929 PIT-treated site is defined as the time from the day of surgery to local regional and/or distant relapse at ASP-1929 PIT-treated site.

PFS defined as time from initial study intervention to progress disease, precluding surgery, locoregional recurrence, distant recurrence, second primary tumor (with biopsy confirmation where possible), or death from any cause.

RFS defined as time from the day of surgery to first recurrence (locoregional or distant)

Overall survival is defined as the time from the first treatment to death from any cause.

Shimadzu Corporation

National Cancer Institute (NCI)

Rakuten Medical, Inc.

Antineoplastic Agents

Pembrolizumab

Patients will receive the approved label dose of pembrolizumab, which is administered every 3 weeks on days 1 and 22 of each treatment cycle.

On Day 8 of each cycle, patients will receive ASP-1929 followed by illumination at accessible tumor sites using the investigational PIT690 Laser System on Day 9.

Each treatment cycle, which is driven by ASP-1929 PIT frequency of administration, will last 42 days. Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 12 months with a maximum of 8 treatment cycles.

ASP-1929 Photoimmunotherapy with pembrolizumab

A Phase 2 Single-arm Study of ASP-1929 Photoimmunotherapy Combined With Pembrolizumab in Patients With Locoregional Recurrent Squamous Cell Carcinoma of the Head and Neck, With or Without Metastases, Not Amenable to Curative Local Treatment

A Single-arm Study of ASP-1929 Photoimmunotherapy Combined With Pembrolizumab.

Patients will receive the approved label dose of pembrolizumab, which is administered every 3 weeks on days 1 and 22 of each treatment cycle.

On Day 8 of each cycle, patients will receive ASP-1929 followed by illumination at accessible tumor sites using the investigational PIT690 Laser System on Day 9.

Each treatment cycle, which is driven by ASP-1929 PIT frequency of administration, will last 42 days. Patients will be treated with ASP-1929 PIT and pembrolizumab for up to 12 months with a maximum of 8 treatment cycles.

ASP-1929 Photoimmunotherapy Combined With Pembrolizumab

ASP-1929 Photoimmunotherapy Combined With Pembrolizumab in Patients With Recurrent Head and Neck Cancer, With or Without Metastases

the proportion of patients with confirmed PIT-treated tumor response of complete response (CR) or partial response (PR) per RECIST 1.1, as assessed by central reviewer.

Duration of Response (DoR; Duration of Response is defined as the time from first response (CR or PR) to the time of disease progression (PD) of PIT-treated lesions per RECIST 1.1, as assessed by central reviewer.

Disease Control Rate (complete response, CR + partial response, PR + stable disease, SD) for PIT-treated lesions per RECIST 1.1, as assessed by central reviewer.

For all lesions per RECIST 1.1, as assessed by central reviewer:

• Confirmed ORR (CR or PR)

For all lesions per RECIST 1.1, as assessed by central reviewer:

• Disease control rate (DCR)

For all lesions per RECIST 1.1, as assessed by central reviewer:

• DoR

Proportion of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs) by Common Terminology Criteria for Adverse Events (CTCAE) v5.0.

Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). It has four-point scales for the first 28 items. The minimum value is 1 and maximum value is 4. Higher scores mean a worse outcome. Overall health was evaluated as a 7-point response scale as the other two questions in that scale. The minimum value is 1 and maximum value is 7. Higher scores mean a better outcome.

Change from baseline in EORTC head and neck specific module (EORTC QLQ H\&N 35). It has 4-point scales for the first 30 items. The minimum value is 1 and maximum value is 4. It has 2-point scales for the last 5 items. The minimum value is 1 and maximum value is 2. For all items and scales, high scores indicate more problems.

Proportion of patients who achieve a clinically meaningful benefit in symptoms, as measured by a 5-point improvement in Functional Assessment of Cancer Therapy Head \& Neck Cancer Symptom Index - 10 Item (FHNSI-10) from baseline to measured best assessment. The minimum value is 0 and maximum value is 4. Higher scores mean a worse outcome.

Area under the concentration-time curve from time 0 through the last measurable time point.

Area under the concentration-time curve from time 0 until 26 hours after infusion initiation (just prior to light treatment).

Area under the concentration-time curve from time 0 through the last measurable time point and extrapolated to infinity.

Area under the concentration-time curve using all available data from 0 through 2 weeks post dose.

The observed terminal elimination half-life.

The volume of serum cleared of drug per unit time following IV dosing (ASP-1929 only).

Volume of distribution following IV dosing (ASP-1929 only).

Proportion of patients with anti-ASP-1929 antibodies.

Antirheumatic Agents

Reproductive Control Agents

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Cetuximab

Methotrexate

docetaxel, cetuximab, methotrexate, paclitaxel

Physician's Choice SOC

Bogdan Veresh, MD

Tien Nguyen

Matthew J. Mifsud, MD

Frank Akuchie

Charles E. Moore, MD

Grace San Agustin

Jeffrey Hotaling, MD

Camilo Henao

David Cognetti, MD

Ethan Skinner

Karthik Rajasekaran, MD

Bridget Reeves

Ann Gillenwater, MD

Yash Damor

Rajesh Kantharia

S. Deyva Manohari

Venkatraman Radhakrishnan

Christy Lee

Pei-Jen Lou

Chia Hui Lin

Chun-Hung Hua

I-Chen Tsai

Chen-Chi Wang

Lora Chang

Kai-Ping Chang

Naomi Schechter

A Phase 3, Randomized, Double-Arm, Open-Label, Controlled Trial of ASP-1929 vs Physician's Choice Standard of Care for the Treatment of Locoregional, Recurrent Head and Neck Squamous Cell Carcinoma in Patients Who Have Failed or Progressed On or After at Least Two Lines of Therapy

The study will have an Experimental Arm and a Control Arm.

Experimental Arm:

Patients may receive repeated ASP-1929 PIT interventions for up to a maximum of 8 cycles within a period of up to 12 months after randomization until the patient has complete remission, progressive disease that is no longer amendable to study treatment, patient experiences intolerable side effects, or patient discontinues study treatment. Repeat ASP-1929 treatment cycles will be administered no less than 4 weeks from the previous ASP-1929 infusion.

Control Arm:

Patients may be treated with physician's choice standard of care until the patient has progressive disease, patient experiences intolerable side effects, discontinues study treatment, or chooses to withdraw.

ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy

A Phase 3, Randomized, Double-Arm, Open-Label, Controlled Trial of ASP-1929 Photoimmunotherapy Versus Physician's Choice Standard of Care for the Treatment of Locoregional, Recurrent Head and Neck Squamous Cell Carcinoma in Patients Who Have Failed or Progressed On or After at Least Two Lines of Therapy, of Which at Least One Line Must Be Systemic Therapy

PFS, defined as the time from randomization to the first occurrence of disease progression (PD), as determined by the investigator according to RECIST 1.1, or death from any cause, whichever one occurs first.

OS, defined by the time interval between the patient randomization and death due to any cause.

ORR, defined by the percentage of patients with the best overall response of complete response (CR) or partial response (PR) by RECIST 1.1. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

CR, defined as disappearance of all target lesions, as determined by Central Radiographic Review according to RECIST 1.1 criteria with modifications. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10mm.

CR by histopathologic biopsy of target tumor(s) and a repeat confirmatory histopathologic CR biopsy at least 3 months after initial CR histopathologic biopsy of the target tumor(s) for patients that do not demonstrate a CR by RECIST 1.1 with modifications. CR: Disappearance of all target lesions.

DoR, defined as the time from first objective response (CR or PR) to the date of the first documented tumor progression, as determined by Central Radiographic Review according to RECIST 1.1 criteria with modifications or date of death due to any cause, whichever occurs first. CR: Disappearance of all target lesions. PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

EFS, defined as the time interval from randomization to a \>20% increase in tumor size from baseline (defined as CT scan at screening) by RECIST 1.1 with modifications, development of new locoregional disease, distant metastatic disease, or death.

Change from baseline in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). EORTC QLQ-C30 is a 30-item questionnaire developed to assess QoL of head and neck cancer participants and consists of five functional scales (physical, role, cognitive, emotional, and social), three symptom scales (fatigue, pain, and nausea and vomiting), a global health status scale, and a number of single items assessing additional symptoms commonly reported by cancer patients (dyspnoea, loss of appetite, insomnia, constipation and diarrhea) and perceived financial impact of the disease. It has four-point scales for the first 28 items. The minimum value is 1 and maximum value is 4. Higher scores mean a worse outcome. Overall health was evaluated as a 7-point response scale as the other two questions in that scale. The minimum value is 1 and maximum value is 7. Higher scores mean a better outcome.

Change from baseline in EORTC head and neck specific module (EORTC QLQ H\&N 35). EORTC QLQ-H\&N35 is a 35-item questionnaire developed to assess QoL of head and neck cancer participants and consists of 7 multiple-item scales that assess the symptom of pain, swallowing, senses (taste/smell), speech, social eating, social contact and sexuality. Also, six single-item scales are included to survey the presence of symptomatic problems associated with teeth, mouth=opening, dry mouth, sticky saliva, coughing, and feeling ill. The minimum value is 1 and maximum value is 4. It has 2-point scales for the last 5 items. The minimum value is 1 and maximum value is 2. For all items and scales, high scores indicate more problems.

Change from baseline in EuroQol 5-Dimension 5-Level (EQ 5D-5L) Questionnaire. EQ-5D-5L is a 5-dimension (mobility, self-care, usual activities, pain/discomfort, anxiety/depression) questionnaire developed to assess the patient-generated health state index score from the societal perspective and subjective perceived health. For each dimension, levels of perceived problems are coded from level 1 (minimum) to level 5 (maximum): no problems (1), slight problems (2), moderate problems (3), severe problems (4), and extreme problems/inability (5). A second part of the questionnaire provides a visual analogue scale (VAS) for individually perceived health from 0 to 100 (corresponding to the worst to the best imaginable health).

Estimate covariate effects of ASP-1929 PK through compartmental PK modeling.

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients with locally advanced cuSCC or HNSCC or metastatic disease that has recurred or progressed, despite all available standard therapies.

RM-1995 will be administered by intravenous (IV) infusion followed approximately 24 hours later by tumor illumination with 690 nm non thermal red light using the PIT690 Laser System. The starting dose of RM-1995 will be 0.25 mg/kg and escalated up to 2.0 mg/kg over 6 dosing cohorts

RM-1995

Pembrolizumab (200 mg) will be administered by intravenous (IV) infusion one week before the first RM-1995 PIT treatment and the second dose three weeks later for patients in the combination arm. Once the DLT window is complete, pembrolizumab dosage will be maintained at either 200 mg Q3w, or shift to 400 mg Q6w, per investigator discretion.

A phase 1a/1b, open-label, RM-1995 drug-dose escalation study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of RM-1995 photoimmunotherapy treatment as monotherapy (phase 1a) or combined with pembrolizumab (phase 1b) in patients with cutaneous squamous cell carcinoma (cuSCC) or head and neck squamous cell carcinoma (HNSCC) that has progressed despite all available standard therapies.

Enrollment consists of six cohorts of patients with locally advanced cuSCC or HNSCC that has recurred or progressed on or after at least one prior line of therapy, which must include prior platinum-based chemotherapy and is not eligible for further locoregional therapy, or with metastatic disease that has recurred or progressed after all available standard therapies. Patients will receive anti-CD25 antibody, conjugated to the light-activatable dye, IRDye® 700DX, followed by illumination with non-thermal red light (RM-1995 photoimmunotherapy)) as monotherapy (phase 1a), or in combination with pembrolizumab (phase 1b).

Patients are required to have measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1,Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2, and a superficial lesion accessible to photoimmunotherapy at the time of screening.

Phase 1a primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment as monotherapy and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD).

Phase 1b primary objectives are to evaluate the safety and tolerability of RM-1995 photoimmunotherapy treatment in combination with pembrolizumab and determine the MTD or MAD.

RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced CuSCC and HNSCC

A Phase 1 First-in-Human, Drug-dose Escalation Study of RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced Cutaneous Squamous Cell Carcinoma or With Head and Neck Squamous Cell Carcinoma

Incidence of dose-limiting toxicities (DLTs), frequency of adverse events, and MTD or MAD

Objective Response Rate (ORRPIT) defined as the proportion of patients with confirmed PIT-treated tumor response of complete response or partial response per RECIST 1.1 (or irRECIST for patients receiving pembrolizumab combination therapy)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Novel Treatment for Metastatic Melanoma	NCT00758797	Metastatic Mela...	Photoimmunother...	18 Years -	Northwestern University
ASP-1929 Photoimmunotherapy (PIT) Study in Patients With Recurrent Head/Neck Cancer	NCT05182866	Head and Neck C... Squamous Cell C...	ASP-1929 Photoi...	18 Years -	Rakuten Medical, Inc.
ASP-1929 Photoimmunotherapy Combined With Pembrolizumab in Patients With Recurrent Head and Neck Cancer, With or Without Metastases	NCT05265013	Head and Neck C...	ASP-1929 Photoi...	20 Years -	Rakuten Medical, Inc.
ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy	NCT03769506	Head and Neck C...	ASP-1929 Photoi... Physician's Cho...	18 Years -	Rakuten Medical, Inc.
ASP-1929 Photoimmunotherapy (PIT) Study in Recurrent Head/Neck Cancer for Patients Who Have Failed at Least Two Lines of Therapy	NCT03769506	Head and Neck C...	ASP-1929 Photoi... Physician's Cho...	18 Years -	Rakuten Medical, Inc.
RM-1995 Photoimmunotherapy, as Monotherapy or Combined With Pembrolizumab, in Patients With Advanced CuSCC and HNSCC	NCT05220748	Cutaneous Squam... Head and Neck S...	RM-1995 Pembrolizumab	18 Years -	Rakuten Medical, Inc.

Spots Global Cancer Trial Database for photoimmunotherapy