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Monoclonal Antibodies

DS-8201a + Pembrolizumab for Breast and Lung Cancer

Phase 1

Recruiting

Research Sponsored by Daiichi Sankyo

Eligibility Criteria Checklist

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

Must have

Pathologically documented, locally advanced/metastatic breast cancer that has centrally determined HER2-low expression (immunohistochemistry [IHC] 1+ or IHC 2+/in situ hybridization [ISH-])

Received prior trastuzumab emtansine (T-DM1) therapy with documented progression

Must not have

Unresolved toxicities from previous anticancer therapy

Prior therapy with an anti-PD-1 or anti-PD-L1 agent

Timeline

Screening 3 weeks

Treatment Varies

Follow Up cycle 1, day 1: predose and postdose, day 8, and day 15; cycle 2, day 1 predose and postdose, and cycle 3, day 1 (each cycle is 21 days)

Awards & highlights

No Placebo-Only Group

Summary

This trial will test a new cancer treatment combining two drugs, one of which is a new experimental drug. The first part will determine how much of the new experimental drug is safe to use. The second part will test how well the combination of the two drugs works, how safe it is, and how well tolerated it is.

Who is the study for?

Adults (≥18 years) with advanced/metastatic breast cancer that is HER2-positive or HER2-low, and those with similar stages of NSCLC. Participants must have tried all other beneficial treatments or be unable to tolerate them. They should not have had prior treatment with pembrolizumab/DS-8201a, severe heart issues within the last 6 months, active hepatitis B/C, certain lung conditions, autoimmune diseases requiring steroids/immunosuppressants, or a history of severe allergic reactions to similar drugs.

What is being tested?

The trial tests DS8201a combined with Pembrolizumab in two parts: first to find the best dose and then to check how well it works and its safety. It's for people whose breast or lung cancer has spread and expresses a protein called HER2. The study aims to see if this drug combo can help when other treatments haven't worked.

What are the potential side effects?

Possible side effects include allergic reactions to the medication components, potential heart problems like QT interval prolongation which affects heartbeat rhythm, liver issues due to hepatitis infection risks, lung complications such as pneumonitis from inflammation, immune system disorders that could worsen due to immunosuppressive medications needed for treatment.

Eligibility Criteria

Inclusion Criteria

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

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My breast cancer is advanced and tests show low HER2 levels.

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My cancer progressed after receiving T-DM1 therapy.

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

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My breast cancer is advanced or has spread, and tests show it's HER2 positive.

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My advanced lung cancer is HER2 positive.

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I am 18 years old or older.

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My breast or lung cancer is advanced and tests show it's HER2 positive.

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I am willing to undergo tumor biopsies.

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My lung cancer is advanced or has spread and tests show a HER2 mutation.

Exclusion Criteria

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

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I still have side effects from past cancer treatments.

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I have been treated with drugs targeting PD-1 or PD-L1.

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I stopped a cancer treatment due to a severe immune reaction.

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I have been treated with pembrolizumab or DS-8201a before.

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I have not taken high-dose steroids or immunosuppressants in the last 14 days.

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I do not have active brain metastases or spinal cord compression.

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I have an autoimmune disease.

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I am currently being treated for an infection.

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I have had an organ or stem cell transplant.

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I do not have an infection needing IV drugs.

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I have severe lung problems due to other lung diseases.

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I have been diagnosed with HIV.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ cycle 1, day 1: predose and postdose, day 8, and day 15; cycle 2, day 1 predose and postdose, and cycle 3, day 1 (each cycle is 21 days)

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~cycle 1, day 1: predose and postdose, day 8, and day 15; cycle 2, day 1 predose and postdose, and cycle 3, day 1 (each cycle is 21 days)

This trial's timeline: 3 weeks for screening, Varies for treatment, and cycle 1, day 1: predose and postdose, day 8, and day 15; cycle 2, day 1 predose and postdose, and cycle 3, day 1 (each cycle is 21 days) for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Dose-limiting toxicities (DLTs), Part 1

Secondary study objectives

Pharmacokinetic Parameter Area Under the Concentration-time Curve (AUC)

Pharmacokinetic Parameter Maximum Serum Concentration (Cmax)

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

Localised oedema

Ear pain

Urinary tract infection

Hyperkalaemia

Erythema

Oral pain

Abdominal pain upper

Arthralgia

Anxiety

Febrile neutropenia

Dyspepsia

Saliva altered

Back pain

Oedema peripheral

Hypertension

Dyspnoea

Nasopharyngitis

Alopecia

Dry skin

Pneumonia aspiration

Sepsis

Trismus

Pneumonitis

Laryngeal oedema

Malnutrition

Pharyngeal haemorrhage

Cellulitis

Septic shock

Clostridium difficile colitis

Cardiac arrest

Systemic infection

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

Pembrolizumab + CRT Followed by Pembrolizumab

Placebo + CRT Followed by Placebo

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: Part 1 (Dose Escalation)Experimental Treatment2 Interventions

HER2-positive breast cancer, HER2-low expressing breast cancer, HER2-expressing NSCLC, and HER2-mutant NSCLC participants who received escalating doses of DS8201a (initial dose 3.2 mg/kg Q3W) and pembrolizumab 200 mg.

Group II: HER2-positive breast cancer (Part 2 Dose Expansion)Experimental Treatment2 Interventions

HER2-positive breast cancer participants with prior ado-trastuzumab emtansine (T-DM1) with disease progression and who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group III: HER2-mutant NSCLC (Part 2 Dose Expansion)Experimental Treatment2 Interventions

HER2-mutant NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group IV: HER2-low breast cancer (Part 2 Dose Expansion)Experimental Treatment2 Interventions

HER2 low breast cancer participants with prior failed standard treatments who received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Group V: HER2-expressing NSCLC (Part 2 Dose Expansion)Experimental Treatment2 Interventions

HER2-expressing NSCLC participants who had not received any prior treatment with anti-PD-1, anti-PD-L1, or HER2 agents and received DS8201a at the RDE in combination with pembrolizumab 200 mg.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Pembrolizumab

2017

Completed Phase 3

~3130

0 / 21Eligibility criteria met