What side effects are associated with this type of intervention?

Common treatments for Oral Squamous Cell Carcinoma (OSCC) include platinum-based chemotherapy (e.g., cisplatin), taxanes (e.g., paclitaxel), and immunotherapy agents (e.g., pembrolizumab). Cisplatin is associated with nephrotoxicity, ototoxicity, and severe nausea and vomiting. Paclitaxel can cause neuropathy, myelosuppression, and hypersensitivity reactions. Pembrolizumab, an immunotherapy agent, may lead to immune-related adverse effects such as colitis, pneumonitis, and endocrinopathies. These treatments can also cause general side effects like fatigue, mucositis, and increased risk of infections.

What prior FDA approvals exist?

FDA-approved treatments for Oral Squamous Cell Carcinoma (OSCC) include pembrolizumab, a PD-1 inhibitor, which has shown efficacy in recurrent or metastatic head and neck squamous cell carcinoma. Cetuximab, an EGFR inhibitor, is also approved and often used in combination with platinum-based chemotherapy (e.g., cisplatin) and 5-fluorouracil. These treatments target specific pathways involved in cancer cell growth and survival, similar to the investigational approaches in the TPST-1495 trial.

What other types of research exist?

Promising novel alternatives to TPST-1495 for Oral Squamous Cell Carcinoma patients include BMS-690514, an oral tyrosine kinase inhibitor targeting ErbB and VEGF receptors, and gefitinib (ZD1839, Iressa), which has shown activity in recurrent or metastatic head and neck cancer. Additionally, ongoing studies with pembrolizumab, an immune checkpoint inhibitor, in combination with other agents like TPST-1495, may offer new therapeutic options.

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Monoclonal Antibodies

TPST-1495 + Pembrolizumab for Cancer

Phase 1

Waitlist Available

Research Sponsored by Tempest Therapeutics

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Aspartate transaminase (AST) and alanine transaminase (ALT) ≤ 2.5 × ULN; for subjects with liver metastases, AST or ALT ≤ 5 × ULN

Subjects must have a tumor that is at least 1 cm in a single dimension and is radiographically apparent on CT or MRI.

Must not have

Active autoimmune disease or inflammatory disorders including inflammatory bowel disease (e.g., ulcerative colitis or Crohn's disease) requiring systemic treatment (i.e., with use of disease modifying agents, systemic corticosteroids or immunosuppressive drug) within 2 years prior to treatment initiation.

Radiation therapy for bone metastasis within 2 weeks, any other external radiation therapy within 4 weeks before treatment initiation. Patients with clinically relevant ongoing complications from prior radiation therapy are not eligible

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from start of treatment to treatment termination visit, up to 24 months

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called TPST-1495 alone and with pembrolizumab to treat various advanced cancers. It focuses on patients whose cancers have no remaining standard treatments. TPST-1495 blocks signals that help tumors grow, while pembrolizumab helps the immune system fight the cancer. Pembrolizumab has been widely studied and used in various cancers, showing effectiveness and safety.

Who is the study for?

This trial is for adults with advanced solid tumors that are metastatic or unresectable, and no standard therapy remains. It's open to all solid tumor types but focuses on colorectal, head and neck squamous cell, urothelial, endometrial cancers, NSCLC, and gastric adenocarcinomas. Participants must have a life expectancy of at least 12 weeks, adequate organ function without recent transfusions or growth factors.

What is being tested?

The study tests TPST-1495 alone or combined with Pembrolizumab in different doses/schedules to find the safest and most effective dose against various solid tumors. The first part determines the maximum tolerated dose; the second part expands testing to specific cancer types.

What are the potential side effects?

Potential side effects include typical reactions from immune therapies such as fatigue, nausea, skin reactions. There may also be risks related to liver enzyme changes due to medication metabolism and possible immune-related complications.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My liver enzymes are within the required limits.

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My tumor is at least 1 cm big and can be seen on a scan.

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I am fully active or restricted in physically strenuous activity but can do light work.

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My kidney function, measured by creatinine or its clearance, is within the required range.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I haven't needed systemic treatment for an autoimmune or inflammatory disorder in the last 2 years.

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I haven't had radiation for bone metastasis in the last 2 weeks or any other radiation in the last 4 weeks.

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I haven't had any cancer treatment with antibodies or chemotherapy in the last 4 weeks.

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I haven't taken any experimental drugs recently.

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I do not have HIV, active Hepatitis B or C, and am not on antiviral therapy for these conditions.

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I do not have any serious ongoing illnesses that could affect my participation in the study.

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I haven't taken any TKI cancer drugs in the last 2 weeks or 5 half-lives.

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I am on blood thinners or have a bleeding disorder.

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I have had allergic reactions or stomach issues from pain relievers like ibuprofen.

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I have taken more than 4 doses of NSAIDs or COX-2 inhibitors in the last 2 weeks.

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My heart condition limits my physical activity.

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I have active or untreated brain metastases.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from start of treatment to treatment termination visit, up to 24 months

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from start of treatment to treatment termination visit, up to 24 months

This trial's timeline: 3 weeks for screening, Varies for treatment, and from start of treatment to treatment termination visit, up to 24 months for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Determination of maximum tolerated dose and/or recommended Phase 2 dose (RP2D) and optimum dose schedule for TPST-1495 as a single agent and in combination with pembrolizumab

Secondary study objectives

Assess pharmacokinetics: Clearance (CL)

Assess pharmacokinetics: area under the serum concentration-time curve (AUC)

Assess pharmacokinetics: maximum serum concentration (Cmax)

+5 more

Side effects data

From 2024 Phase 3 trial • 804 Patients • NCT03040999

64%

Radiation skin injury

63%

Stomatitis

58%

Anaemia

56%

Nausea

48%

Dry mouth

45%

Constipation

45%

Weight decreased

44%

Dysphagia

42%

Neutrophil count decreased

33%

Dysgeusia

33%

Vomiting

32%

Fatigue

31%

White blood cell count decreased

28%

Hypomagnesaemia

26%

Decreased appetite

25%

Hypothyroidism

25%

Hypokalaemia

24%

Lymphocyte count decreased

24%

Platelet count decreased

23%

Oropharyngeal pain

23%

Blood creatinine increased

22%

Diarrhoea

22%

Odynophagia

20%

Hypoacusis

20%

Alanine aminotransferase increased

20%

Hyponatraemia

19%

Tinnitus

19%

Oral candidiasis

19%

Asthenia

16%

Pyrexia

16%

Cough

15%

Aspartate aminotransferase increased

15%

Rash

14%

Insomnia

13%

Acute kidney injury

13%

Pharyngeal inflammation

13%

Pruritus

12%

Dysphonia

12%

Gamma-glutamyltransferase increased

11%

Pneumonia

11%

Dehydration

10%

Hyperthyroidism

10%

Hypoalbuminaemia

10%

Hypocalcaemia

10%

Headache

10%

Productive cough

Neck pain

Peripheral sensory neuropathy

Gastrooesophageal reflux disease

Hiccups

Hyperglycaemia

Hyperuricaemia

Dizziness

Hypophosphataemia

Urinary tract infection

Ear pain

Localised oedema

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Sepsis

Pneumonia aspiration

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Systemic infection

Cardiac arrest

Death

Bronchitis

Hepatitis

Immune-mediated hepatitis

Oesophagitis

General physical health deterioration

Hypophagia

Tumour haemorrhage

Cerebrovascular accident

Syncope

Acute respiratory failure

Aspiration

Colitis

Mouth haemorrhage

Hypersensitivity

Acute myocardial infarction

Abscess neck

Device related infection

Stoma site infection

Vascular device infection

Wound infection

Hypercalcaemia

Pulmonary embolism

Respiratory failure

100%

80%

60%

40%

20%

Study treatment Arm

Placebo + CRT Followed by Placebo

Pembrolizumab + CRT Followed by Pembrolizumab

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

5Treatment groups

Experimental Treatment

Group I: TPST-1495 monotherapy dose expansionExperimental Treatment1 Intervention

Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Group II: TPST-1495 monotherapy dose escalationExperimental Treatment1 Intervention

Subjects will receive escalating doses of TPST-1495 administered orally twice daily until maximum tolerated dose is reached or until disease progression

Group III: TPST-1495 monotherapy dose and schedule optimizationExperimental Treatment1 Intervention

Subjects will receive alternative TPST-1495 administration schedules until RP2D for the selected schedule is determined or until disease progression.

Group IV: TPST-1495 in combination with pembrolizumab dose expansionExperimental Treatment2 Interventions

Subjects will receive selected dose regimen from dose and schedule optimization stage until disease progression

Group V: TPST-1495 in combination with pembrolizumab dose and schedule optimizationExperimental Treatment2 Interventions

Subjects will receive alternative TPST-1495 administration schedules in combination with pembrolizumab until RP2D for the selected schedule is determined or until disease progression.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~2810

0 / 16Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Oral Squamous Cell Carcinoma (OSCC) include surgery, radiation therapy, chemotherapy, and targeted therapy. Surgery physically removes the tumor, while radiation therapy uses high-energy rays to kill cancer cells. Chemotherapy, such as cisplatin, works by damaging the DNA of rapidly dividing cells, leading to cell death. Targeted therapies, like cetuximab, inhibit specific molecules involved in cancer cell growth and survival. Immunotherapy, such as pembrolizumab, enhances the body's immune response against cancer cells by blocking inhibitory pathways that prevent immune cells from attacking tumors. These treatments are crucial for OSCC patients as they offer multiple approaches to control and potentially eradicate the cancer, improving survival rates and quality of life.

Biological agents in head and neck cancer.