First Time in Human Study of AZD8701 With or Without Durvalumab in Participants With Advanced Solid Tumours

AstraZeneca

Status and phase: Completed; Phase 1

Conditions: Melanoma; Small Cell Lung Cancer; Advanced Solid Tumours; Squamous Cell Cancer of Head and Neck; Gastroesophageal Cancer; Triple Negative Breast Neoplasms; Cervical Cancer; Non-Small-Cell Lung Cancer; Clear Cell Renal Cell Cancer

Treatments: Biological: Durvalumab; Drug: AZD8701

Study type: Interventional

Funder types: Industry

Identifiers

NCT04504669

D9950C00001

2019-004539-22 (EudraCT Number)

04504669 (Other Identifier)

Details and patient eligibility

About

The purpose of this study is to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of AZD8701 Alone and in Combination with Durvalumab (MEDI4736) in Adult Subjects with Select Advanced Solid Tumors

Full description

This is a Phase I, First in Human, multicentre, open-label, multiple arm study with dose escalations and expansions at selected doses. Dose-escalation will occur with AZD8701 in monotherapy (Part 1) and in combination with durvalumab (Part 3) in selected participants with HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, small-cell lung cancer and/or participants with solid tumours who have demonstrated a response to prior PD-(L)1 treatment.

Disease specific expansions will occur with a selected dose of AZD8701 in participants with NSCLC (Part 2) and with a selected dose of AZD8701 and durvalumab in participants with TNBC and clear cell RCC (Part 4).

Enrollment: 60 patients

Sex: All

Ages: 18 to 101 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

The study is comprised of 2 main parts Monotherapy (AZD8701) and Combined Therapy (AZD8701 and Durvalumab).

Inclusion criteria Dose escalation stages:

• Histological or cytological confirmation of a solid, malignant tumour including HNSCC, TNBC, NSCLC, ccRCC, gastroesophageal cancer, melanoma, cervical cancer, SCLC, and/or participants with other solid tumours who have demonstrated a response to prior anti-PD-(L)1 treatment
• Participant with progressive disease that is refractory to standard therapies or for which no standard therapies exist and a clinical trial is the best option for next treatment based on prior response and/or tolerability to standard of care

Inclusion Criteria Dose Expansions:

Non Small Lung Cancer Participants who have received prior PD(L)1 treatment. Clear Cell Renal Cancer Participants who have not received prior PD(L)1 treatment.

Triple negative Breast Cancer participants who have who have not received prior PD(L)1 treatment.

General inclusion criteria:

• Must be 18 year old at the time of screening
• Body weight > 35 kg
• Male and Female participants of childbearing potential must use effective methods of contraception
• Capable of giving signed informed consent
• ECOG performance status of 0 to 1
• A serum albumin > 30g/L
• Life expectancy of > 12 weeks
• At least 1 lesion, that qualifies as a RECIST 1.1 target lesion at baseline. Tumour assessment by CT scan or MRI must be performed within 28 days prior to treatment.
• Participants must provide a new or previous tumour sample
• Adequate organ system functions

Exclusion criteria

• A condition that, in the opinion of the Investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results

• History of allogeneic organ transplantation.

• Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness

• Significant cardiac disease

• History of another primary malignancy except for

  1. Malignancy treated with curative intent and with no known active disease ≥ 5 years
  2. non-melanoma skin cancer
  3. Adequately treated carcinoma in situ without evidence of disease.

• Participant with previous or confirmed Covid 19 diagnosis requiring significant medical intervention

• Current clinical signs and symptoms consistent with COVID-19 or confirmed current infection by appropriate laboratory test within the last 4 weeks prior to screening

• Any major unresolved toxicity from previous anticancer therapy

• Known allergy or hypersensitivity to any of the study interventions or any of the study intervention excipients.

Prior/Concomitant Therapy

• Receipt of the last dose of anticancer therapy within 5 half-lives or ≤ 21 days prior to the first dose of study

• Prior treatment with potential Treg depletion therapies including agents targeting OX40 or CD357 (GITR) for 90 days prior to enrolment on study.

• Participants who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4:

  1. Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
  2. All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline
  3. Must not have experienced a ≥ Grade 3 imAE or a neurologic or ocular imAE of any grade while receiving prior immunotherapy.
  4. Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE

• Current or prior use of immunosuppressive medication within 14 days before the first dose of study drug. b. The following are exceptions to this criterion:

  1. Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
  2. Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  3. Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication)

• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment

• Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study intervention.

• Major surgical procedure within 28 days prior to the first dose

• Participants receiving anticoagulation therapy with vitamin K antagonists (eg warfarin)

• Participation in another clinical study with study intervention administered in the last 30 days

• Female participants who are pregnant or breastfeeding or male and female participants of reproductive potential who are not willing to employ effective birth control

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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60 participants in 2 patient groups

Monotherapy

Experimental group

Description:

Participants will receive AZD8701 intravenously, on Day 1, 3, 5 and 8 and then weekly for a maximum of 2 years.

Treatment:

Drug: AZD8701

Combination Therapy

Experimental group

Description:

Participants will receive AZD8701 (intravenously, on Day 1, 3, 5 and 8 and then weekly) and durvalumab (MEDI4736) intravenously monthly for a maximum of 2 years.

Treatment:

Drug: AZD8701

Biological: Durvalumab