Study of AMG 650 in Adult Participants With Advanced Solid Tumors

Volastra Therapeutics

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: AMG 650

Study type: Interventional

Funder types: Industry

Identifiers

NCT04293094

20190131

Details and patient eligibility

About

To evaluate the safety and tolerability of AMG 650 in adult participants and to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D).

Enrollment: 66 patients

Sex: All

Ages: 18 to 99 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Male and female ≥ 18 years old
• Triple Negative Breast Cancer participants only: Participant must have histologically or cytologically confirmed metastatic or locally recurrent estrogen receptor (ER)-negative (<1% by immunohistochemistry [IHC]), progesterone receptor (PR)-negative (<1% IHC) and human epidermal growth factor receptor 2 (Her2)-negative (either fluorescent in situ hybridisation [FISH] negative, 0 or 1+ by IHC, or IHC2+ and FISH negative per ASCO/CAP definition) breast cancer. Participant must be relapsed/refractory to at least one line of systemic chemotherapy in the metastatic setting (excluding neoadjuvant or adjuvant chemotherapies) or intolerant of existing therapy(ies) known to provide clinical benefit or have no other available treatment options. Prior exposure to an immune checkpoint inhibitor is allowed.
• Platinum-Resistant High Grade Serous Ovarian Cancer, primary peritoneal cancer and/or fallopian-tube cancer participants only: Participant must have histologically or cytologically confirmed diagnosis of metastatic or unresectable high grade serous ovarian cancer, with platinum-resistance defined as progression during or within 6 months of a platinum-containing regimen, with no other treatment option available. Prior exposure to platinum-resistant recurrence therapy is allowed.
• Serous Endometrial Cancer participants only (Dose Exploration only): Participant must have histologically or cytologically confirmed diagnosis of metastatic or recurrent serous endometrial cancer, and be relapsed/refractory to at least one line of systemic therapy in the metastatic/recurrent setting or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
• Participants with advanced or metastatic solid tumor with TP53MUT (Dose Exploration only, as assessed by local testing) that is unresectable and relapsed/refractory to at least one line of systemic chemotherapy or intolerant.
• TNBC participants only (Dose Expansion): Progressed on no more than 3 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with poly ADP ribose polymerase (PARP) inhibitor will be counted as one line of therapy.
• HGSOC participants only (Dose Expansion): Progressed on no more than 5 prior lines of systemic therapy for locally advanced or metastatic disease (not including adjuvant or neo-adjuvant). Systemic therapy with (PARP) inhibitor will be counted as one line of therapy. Induction followed by maintenance will be counted as one line of therapy.

Exclusion criteria

• Untreated or symptomatic brain metastases and leptomeningeal disease (exception: benign asymptomatic tumors are permitted).
• Current primary CNS tumor, hematological malignancies or lymphoma.
• Uncontrolled pleural effusions(s), pericardial effusion, or ascites.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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66 participants in 3 patient groups

Dose Exploration Phase

Experimental group

Description:

Participants will receive AMG 650 in 1 of 3 alternative schedules. The maximum tolerated dose (MTD) of each schedule will be estimated using isotonic regression (Ji et al, 2010). The Recommended Phase 2 Dose (RP2D) may be identified based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching an MTD.

Treatment:

Drug: AMG 650

Dose Expansion Phase Group 1: TNBC

Experimental group

Description:

Participants with locally advanced or metastatic triple negative breast cancer (TNBC), will be administered with the preliminary RP2D identified from the dose exploration part of the study.

Treatment:

Drug: AMG 650

Dose Expansion Phase Group 2: HGSOC

Experimental group

Description:

Participants with locally advanced or metastatic high grade serous ovarian cancer (HGSOC), will be administered with the preliminary RP2D identified from the dose exploration part of the study.

Treatment:

Drug: AMG 650