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

Prior treatment

• Active or prior documented autoimmune or inflammatory disorders Uncontrolled intercurrent illness
• History of another primary malignancy except for
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years
  • non-melanoma skin cancer
  • Adequately treated carcinoma in situ without evidence of disease.
• Participant with previous or confirmed Covid 19 diagnosis requiring significant medical intervention
• 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:
  • Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
  • All AEs while receiving prior immunotherapy must have completely resolved or resolved to baseline
  • Must not have experienced a ≥ Grade 3 imAE or a neurologic or ocular imAE of any grade while receiving prior immunotherapy.
  • 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:
  • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra-articular injection).
  • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
  • 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)

Other illness

• 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.
• Significant cardiac disease

Lab values

• 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

Other

• 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

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