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PD-1 Inhibitor

Talimogene Laherparepvec + Pembrolizumab for Melanoma

Phase 2

Waitlist Available

Research Sponsored by Amgen

Eligibility Criteria Checklist

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

Must have

Age ≥ 18 years with histologically confirmed diagnosis of stage IIIB to IVM1d melanoma and for whom surgery is not recommended

Subjects must have had prior treatment (for at least 2 to 3 consecutive cycles within an 8 week period) with a PD-1 inhibitor and have confirmed disease progression (as defined by RECIST v1.1 criteria). The anti-PD-1 therapy must be the immediate prior line of therapy before enrollment and subjects with disease progression on more than 1 line of anti-PD-1 therapy are not eligible

Must not have

Subjects must not have active herpetic skin lesions or prior complications of herpetic infection and must not require intermittent or chronic treatment with an antiherpetic drug (eg, acyclovir), other than intermittent topical use

Subjects with prior treatment and disease progression on more than 1 line of anti-PD-1 therapy

Timeline

Screening 3 weeks

Treatment Varies

Follow Up every 12 weeks up to 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new cancer treatment combining two drugs, talimogene laherparepvec and pembrolizumab. The treatment will be given to people with unresectable/metastatic melanoma (stage IIIB-IVM1d) or prior adjuvant therapy who have progressed on prior anti-PD-1 therapy. The study will evaluate the efficacy and safety of the treatment.

Who is the study for?

This trial is for adults over 18 with stage IIIB to IVM1d melanoma that can't be removed by surgery. They must have tried a PD-1 inhibitor therapy and seen their cancer grow despite this treatment. Participants should be in good physical condition, able to perform daily activities (ECOG status of 0 or 1), and have no more than three treated brain metastases without recent steroid use.

What is being tested?

The study tests talimogene laherparepvec combined with pembrolizumab in patients whose melanoma worsened after anti-PD-1 therapy. It's an open-label, phase 2 trial where all participants receive the same treatment until they either respond completely, run out of lesions that can be injected, experience intolerable side effects, see further disease progression, or complete 102 weeks of treatment.

What are the potential side effects?

Possible side effects include reactions at the injection site for talimogene laherparepvec, flu-like symptoms such as fever and chills, fatigue from pembrolizumab; both drugs may also cause immune-related issues affecting organs like the liver or intestines.

Eligibility Criteria

Inclusion Criteria

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

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I am over 18 and have advanced melanoma that cannot be removed by surgery.

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I've had PD-1 inhibitor treatment for my cancer, which didn't work.

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I have visible tumors that can be treated by direct injection.

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I am fully active or can carry out light work.

Exclusion Criteria

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

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I don't have active herpes skin sores or need regular herpes medication.

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My condition worsened after treatment with more than one anti-PD-1 therapy.

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I have melanoma with no more than 3 brain metastases and don't need treatment for them.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ every 12 weeks up to 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~every 12 weeks up to 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and every 12 weeks up to 4 years for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Objective Response Rate (ORR) Per Modified RECIST v1.1

Secondary study objectives

BOR Per Modified RECIST v1.1

Best Overall Response (iBOR) Per Modified irRC-RECIST

Complete Response Rate (CRR) Per Modified RECIST v1.1

+13 more

Side effects data

From 2014 Phase 3 trial • 437 Patients • NCT00769704

50%

Fatigue

48%

Chills

41%

Pyrexia

36%

Nausea

30%

Influenza like illness

28%

Injection site pain

21%

Vomiting

19%

Diarrhoea

19%

Headache

17%

Arthralgia

17%

Myalgia

16%

Pain

16%

Pain in extremity

12%

Constipation

12%

Oedema peripheral

11%

Cough

10%

Upper respiratory tract infection

10%

Decreased appetite

10%

Dizziness

10%

Pruritus

Abdominal pain

Back pain

Rash

Hyperhidrosis

Erythema

Tumour pain

Anxiety

Insomnia

Oropharyngeal pain

Weight decreased

Dyspepsia

Injection site erythema

Musculoskeletal pain

Neck pain

Depression

Anaemia

Vitiligo

Muscle spasms

Dyspnoea

Injection site reaction

Injection site swelling

Disease progression

Injection site pruritus

Cellulitis

Deep vein thrombosis

Rib fracture

Metastases to central nervous system

Intestinal obstruction

Gastrointestinal haemorrhage

Pleural effusion

Dehydration

Infected neoplasm

Metastatic malignant melanoma

Cerebral haemorrhage

Convulsion

Mental status changes

Pulmonary embolism

Atrial fibrillation

100%

80%

60%

40%

20%

Study treatment Arm

Talimogene Laherparepvec

GM-CSF

Awards & Highlights

No Placebo-Only Group

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

Trial Design

4Treatment groups

Experimental Treatment

Group I: Cohort 4 - Adjuvant Setting -Disease Free Interval ≥ 6 monthsExperimental Treatment2 Interventions

Includes participants who received anti PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of ≥ 6 months after starting the adjuvant PD-1 inhibitor. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Group II: Cohort 3 - Adjuvant Setting -Disease Free Interval < 6 monthsExperimental Treatment2 Interventions

Includes participants who received anti-PD-1 therapy in the adjuvant setting and experienced confirmed disease progression following a disease-free interval of \< 6 months after starting the adjuvant anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Group III: Cohort 2 - Locally Recurrent/Metastatic - Acquired ResistanceExperimental Treatment2 Interventions

Includes participants who received anti-PD-1 therapy in the locally recurrent/metastatic setting and experienced confirmed disease progression following a complete or partial response on anti-PD-1 therapy. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Group IV: Cohort 1 - Locally Recurrent/Metastatic - Primary ResistanceExperimental Treatment2 Interventions

Includes participants who received anti-PD1 therapy in the locally recurrent/metastatic setting and experienced a best overall response of disease progression or stable disease prior to confirmed disease progression. Participants will receive talimogene laherparepvec at an initial dose of up to 4.0 mL of 10\^6 plaque-forming units (PFU)/mL on Day 1. Subsequent doses of up to 4.0 mL of 10\^8 PFU/mL will be administered every 3 weeks for up to 35 cycles in total. Participants will also receive pembrolizumab at a dose of 200 mg every 3 weeks for up to 35 cycles.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Talimogene laherparepvec

2014

Completed Phase 3

~820

Pembrolizumab

2017

Completed Phase 3

~3150